39 results on '"An, Jingjing"'
Search Results
2. O-GlcNAcylation: roles and potential therapeutic target for bone pathophysiology
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Xiaohan Yan, Jingjing Zheng, Wenhao Ren, Shaoming Li, Shuying Yang, Keqian Zhi, and Ling Gao
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Post-translational modification ,O-GlcNAcylation ,Bone pathophysiology ,Medicine ,Cytology ,QH573-671 - Abstract
Abstract O-linked N-acetylglucosamine (O-GlcNAc) protein modification (O-GlcNAcylation) is a critical post-translational modification (PTM) of cytoplasmic and nuclear proteins. O-GlcNAcylation levels are regulated by the activity of two enzymes, O-GlcNAc transferase (OGT) and O‑GlcNAcase (OGA). While OGT attaches O-GlcNAc to proteins, OGA removes O-GlcNAc from proteins. Since its discovery, researchers have demonstrated O-GlcNAcylation on thousands of proteins implicated in numerous different biological processes. Moreover, dysregulation of O-GlcNAcylation has been associated with several pathologies, including cancers, ischemia-reperfusion injury, and neurodegenerative diseases. In this review, we focus on progress in our understanding of the role of O-GlcNAcylation in bone pathophysiology, and we discuss the potential molecular mechanisms of O-GlcNAcylation modulation of bone-related diseases. In addition, we explore significant advances in the identification of O-GlcNAcylation-related regulators as potential therapeutic targets, providing novel therapeutic strategies for the treatment of bone-related disorders.
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- 2024
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3. E26 transformation-specific transcription variant 5 in development and cancer: modification, regulation and function
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Wei, Yi, Han, Shenqi, Wen, Jingyuan, Liao, Jingyu, Liang, Junnan, Yu, Jingjing, Chen, Xiaoping, Xiang, Shuai, Huang, Zhao, and Zhang, Bixiang
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- 2023
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4. E26 transformation-specific transcription variant 5 in development and cancer: modification, regulation and function
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Yi Wei, Shenqi Han, Jingyuan Wen, Jingyu Liao, Junnan Liang, Jingjing Yu, Xiaoping Chen, Shuai Xiang, Zhao Huang, and Bixiang Zhang
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ETV5 ,Post-translational modification ,Immune ,Angiogenesis ,Metastasis ,Cell cycle ,Medicine - Abstract
Abstract E26 transformation-specific (ETS) transcription variant 5 (ETV5), also known as ETS-related molecule (ERM), exerts versatile functions in normal physiological processes, including branching morphogenesis, neural system development, fertility, embryonic development, immune regulation, and cell metabolism. In addition, ETV5 is repeatedly found to be overexpressed in multiple malignant tumors, where it is involved in cancer progression as an oncogenic transcription factor. Its roles in cancer metastasis, proliferation, oxidative stress response and drug resistance indicate that it is a potential prognostic biomarker, as well as a therapeutic target for cancer treatment. Post-translational modifications, gene fusion events, sophisticated cellular signaling crosstalk and non-coding RNAs contribute to the dysregulation and abnormal activities of ETV5. However, few studies to date systematically summarized the role and molecular mechanisms of ETV5 in benign diseases and in oncogenic progression. In this review, we specify the molecular structure and post-translational modifications of ETV5. In addition, its critical roles in benign and malignant diseases are summarized to draw a panorama for specialists and clinicians. The updated molecular mechanisms of ETV5 in cancer biology and tumor progression are delineated. Finally, we prospect the further direction of ETV5 research in oncology and its potential translational applications in the clinic.
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- 2023
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5. The Plant PTM Viewer 2.0: in-depth exploration of plant protein modification landscapes.
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Willems, Patrick, Sterck, Lieven, Dard, Avilien, Huang, Jingjing, Smet, Ive De, Gevaert, Kris, and Breusegem, Frank Van
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POST-translational modification ,NUCLEAR proteins ,PLANT proteins ,PLANT enzymes ,GENETIC transcription regulation - Abstract
Post-translational modifications (PTMs) greatly increase protein diversity and functionality. To help the plant research community interpret the ever-increasing number of reported PTMs, the Plant PTM Viewer (https://www.psb.ugent.be/PlantPTMViewer) provides an intuitive overview of plant protein PTMs and the tools to assess it. This update includes 62 novel PTM profiling studies, adding a total of 112 000 modified peptides reporting plant PTMs, including 14 additional PTM types and three species (moss, tomato, and soybean). Furthermore, an open modification re-analysis of a large-scale Arabidopsis thaliana mass spectrometry tissue atlas identified previously uncharted landscapes of lysine acylations predominant in seed and flower tissues and 3-phosphoglycerylation on glycolytic enzymes in plants. An extra 'Protein list analysis' tool was developed for retrieval and assessing the enrichment of PTMs in a protein list of interest. We conducted a protein list analysis on nuclear proteins, revealing a substantial number of redox modifications in the nucleus, confirming previous assumptions regarding the redox regulation of transcription. We encourage the plant research community to use PTM Viewer 2.0 for hypothesis testing and new target discovery, and also to submit new data to expand the coverage of conditions, plant species, and PTM types, thereby enriching our understanding of plant biology. [ABSTRACT FROM AUTHOR]
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- 2024
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6. Cysteine thiol sulfinic acid in plant stress signaling.
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Huang, Jingjing, De Veirman, Lindsy, and Van Breusegem, Frank
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SULFINIC acids , *CYSTEINE , *POST-translational modification , *THIOLS , *CELL communication , *CELLULAR signal transduction , *DISULFIDES - Abstract
Cysteine thiols are susceptible to various oxidative posttranslational modifications (PTMs) due to their high chemical reactivity. Thiol‐based PTMs play a crucial role in regulating protein functions and are key contributors to cellular redox signaling. Although reversible thiol‐based PTMs, such as disulfide bond formation, S‐nitrosylation, and S‐glutathionylation, have been extensively studied for their roles in redox regulation, thiol sulfinic acid (–SO2H) modification is often perceived as irreversible and of marginal significance in redox signaling. Here, we revisit this narrow perspective and shed light on the redox regulatory roles of –SO2H in plant stress signaling. We provide an overview of protein sulfinylation in plants, delving into the roles of hydrogen peroxide‐mediated and plant cysteine oxidase‐catalyzed formation of –SO2H, highlighting the involvement of –SO2H in specific regulatory signaling pathways. Additionally, we compile the existing knowledge of the –SO2H reducing enzyme, sulfiredoxin, offering insights into its molecular mechanisms and biological relevance. We further summarize current proteomic techniques for detecting –SO2H and furnish a list of experimentally validated cysteine –SO2H sites across various species, discussing their functional consequences. This review aims to spark new insights and discussions that lead to further investigations into the functional significance of protein –SO2H‐based redox signaling in plants. Summary statement: This review expands upon the conventional understanding of cysteine thiol sulfinic acid modification and provides an updated overview of its redox‐dependent regulatory functions in the context of plant stress signaling pathways. [ABSTRACT FROM AUTHOR]
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- 2024
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7. Role of O-linked N-acetylglucosamine protein modification in oxidative stress-induced autophagy: a novel target for bone remodeling.
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Li, Shengqian, Ren, Wenhao, Zheng, Jingjing, Li, Shaoming, Zhi, Keqian, and Gao, Ling
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BONE remodeling ,OXIDATIVE stress ,BONE resorption ,N-acetylglucosamine ,AUTOPHAGY ,MESENCHYMAL stem cells ,POST-translational modification - Abstract
O-linked N-acetylglucosamine protein modification (O-GlcNAcylation) is a dynamic post-translational modification (PTM) involving the covalent binding of serine and/or threonine residues, which regulates bone cell homeostasis. Reactive oxygen species (ROS) are increased due to oxidative stress in various pathological contexts related to bone remodeling, such as osteoporosis, arthritis, and bone fracture. Autophagy serves as a scavenger for ROS within bone marrow-derived mesenchymal stem cells, osteoclasts, and osteoblasts. However, oxidative stress-induced autophagy is affected by the metabolic status, leading to unfavorable clinical outcomes. O-GlcNAcylation can regulate the autophagy process both directly and indirectly through oxidative stress-related signaling pathways, ultimately improving bone remodeling. The present interventions for the bone remodeling process often focus on promoting osteogenesis or inhibiting osteoclast absorption, ignoring the effect of PTM on the overall process of bone remodeling. This review explores how O-GlcNAcylation synergizes with autophagy to exert multiple regulatory effects on bone remodeling under oxidative stress stimulation, indicating the application of O-GlcNAcylation as a new molecular target in the field of bone remodeling. [ABSTRACT FROM AUTHOR]
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- 2024
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8. Regulation of Disease-Resistance Genes against CWMV Infection by NbHAG1-Mediated H3K36ac.
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Tu, Aizhu, Wu, Mila, Jiang, Yaoyao, Guo, Lidan, Guo, Yunfei, Wang, Jinnan, Xu, Gecheng, Shi, Jingjing, Chen, Jianping, Yang, Jian, and Zhong, Kaili
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GENETIC regulation ,POST-translational modification ,NICOTIANA benthamiana ,PLANT-pathogen relationships - Abstract
Post-translational modification of proteins plays a critical role in plant–pathogen interactions. Here, we demonstrate in Nicotiana benthamiana that knockout of NbHAG1 promotes Chinese wheat mosaic virus (CWMV) infection, whereas NbHAG1 overexpression inhibits infection. Transcriptome sequencing indicated that a series of disease resistance-related genes were up-regulated after overexpression of NbHAG1. In addition, cleavage under targets and tagmentation (Cut&Tag)-qPCR results demonstrated that NbHAG1 may activate the transcription of its downstream disease-resistance genes by facilitating the acetylation level of H3K36ac. Therefore, we suggest that NbHAG1 is an important positive regulator of resistance to CWMV infestation. [ABSTRACT FROM AUTHOR]
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- 2024
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9. Hydrogen Sulfide Signaling in Plants.
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Huang, Jingjing and Xie, Yanjie
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HYDROGEN sulfide , *PLANT physiology , *ABSCISIC acid , *PLANT growth , *PROTEOMICS , *STOMATA , *POST-translational modification - Abstract
Significance: Hydrogen sulfide (H2S) is a multitasking potent regulator that facilitates plant growth, development, and responses to environmental stimuli. Recent Advances: The important beneficial effects of H2S in various aspects of plant physiology aroused the interest of this chemical for agriculture. Protein cysteine persulfidation has been recognized as the main reduction–oxidation (redox) regulatory mechanism of H2S signaling. An increasing number of studies, including large-scale proteomic analyses and functional characterizations, have revealed that H2S-mediated persulfidations directly regulate protein functions, altering downstream signaling in plants. To date, the importance of H2S-mediated persulfidation in several abscisic acid signaling-controlling key proteins has been assessed as well as their role in stomatal movements, largely contributing to the understanding of the plant H2S-regulatory mechanism. Critical Issues: The molecular mechanisms of the H2S sensing and transduction in plants remain elusive. The correlations of H2S-mediated persulfidation with other oxidative post-translational modifications of cysteines are still to be explored. Future Directions: Implementation of advanced detection approaches for the spatiotemporal monitoring of H2S levels in cells and the current proteomic profiling strategies for the identification and quantification of the cysteine site-specific persulfidation will provide insight into the H2S signaling in plants. Antioxid. Redox Signal. 39, 40–58. [ABSTRACT FROM AUTHOR]
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- 2023
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10. Cysteine thiol-based post-translational modification: What do we know about transcription factors?
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Zhou, Heng, Huang, Jingjing, Willems, Patrick, Van Breusegem, Frank, and Xie, Yanjie
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POST-translational modification , *TRANSCRIPTION factors , *CYSTEINE , *GENETIC regulation , *PROTEIN stability , *REACTIVE oxygen species , *CELLULAR signal transduction - Abstract
Reactive electrophilic species are ubiquitous in plant cells, where they contribute to specific redox-regulated signaling events. Redox signaling is known to modulate gene expression during diverse biological processes, including plant growth, development, and environmental stress responses. Emerging data demonstrates that transcription factors (TFs) are a main target of cysteine thiol-based oxidative post-translational modifications (OxiPTMs), which can alter their transcriptional activity and thereby convey redox information to the nucleus. Here, we review the significant progress that has been made in characterizing cysteine thiol-based OxiPTMs, their biochemical properties, and their functional effects on plant TFs. We discuss the underlying mechanism of redox regulation and its contribution to various physiological processes as well as still outstanding challenges in redox regulation of plant gene expression. Reactive electrophilic species, including reactive oxygen, nitrogen, and sulfur species (ROS/RNS/RSS), actively contribute to redox signal transduction in diverse signaling processes. Hydrogen peroxide (H 2 O 2), nitric oxide (NO), and hydrogen sulfide (H 2 S) are the most studied ROS/RNS/RSS, respectively. The biological function of H 2 O 2 /NO/H 2 S is largely governed through oxidative post-translational modifications (OxiPTMs) of proteins that impact protein function. An expanding list of transcription factors undergoes OxiPTMs and has been found to contribute to redox signaling–regulated transcription reprogramming in plant development and stress responses. OxiPTMs can alter the DNA binding ability, subcellular localization, protein stability, phase separation, and/or protein–protein interactions of transcription factors. [ABSTRACT FROM AUTHOR]
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- 2023
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11. Dissecting the essential role of N-glycosylation in catalytic performance of xanthan lyase.
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Zhao, Jingjing, Wang, Qian, Ni, Xin, Shen, Shaonian, Nan, Chenchen, Li, Xianzhen, Chen, Xiaoyi, and Yang, Fan
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LIQUID chromatography-mass spectrometry ,GLYCINE receptors ,SITE-specific mutagenesis ,ASPARTIC acid ,FLUORESCENCE spectroscopy ,TERTIARY structure ,GLYCANS ,POST-translational modification - Abstract
Modified xanthan produced by xanthan lyase has broad application prospects in the food industry. However, the catalytic performance of xanthan lyase still needs to be improved through rational design. To address this problem, in this work, the glycosylation and its influences on the catalytic performance of a xanthan lyase (EcXly), which was heterologously expressed in Escherichia coli, were reported. Liquid chromatography coupled to tandem mass spectrometry analysis revealed that the N599 site of EcXly was modified by a single N-glycan chain. Based on sequence alignment and three-dimensional structure prediction, it could be deduced that the N599 site was located in the catalytic domain of EcXly and in close proximity to the catalytic residues. After site-directed mutagenesis of N599 with alanine, aspartic acid and glycine, respectively, the EcXly and its mutants were characterized and compared. The results demonstrated that elimination of the N-glycosylation had diminished the specific activity, pH stability, and substrate affinity of EcXly. Fluorescence spectra further revealed that the glycosylation could significantly affect the overall tertiary structure of EcXly. Therefore, in prokaryotic hosts, the N-glycosylation could influence the catalytic performance of the enzyme by changing its structure. To the best of our knowledge, this is the first report about the post-translational modification of xanthan lyase in prokaryotes. Overall, our work enriched research on the role of glycan chains in the functional performance of proteins expressed in prokaryotes and should be valuable for the rational design of xanthan lyase to produce modified xanthan for industrial application. [ABSTRACT FROM AUTHOR]
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- 2022
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12. Posttranslational modification of Aurora A‐NSD2 loop contributes to drug resistance in t(4;14) multiple myeloma.
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Jiang, Hongmei, Wang, Yixuan, Wang, Jingjing, Wang, Yafei, Wang, Sheng, He, Enyang, Guo, Jing, Xie, Ying, Wang, Jingya, Li, Xin, Peng, Ziyi, Wang, Mengqi, Hou, Jian, and Liu, Zhiqiang
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POST-translational modification ,MULTIPLE myeloma ,DRUG resistance ,AURORA kinases ,CYTOGENETICS - Abstract
Background: t(4;14)(p16;q32) cytogenetic abnormality renders high level of histone methyltransferase NSD2 in multiple myeloma (MM) patients, and predicts poor clinical prognosis, but mechanisms of NSD2 in promoting chemoresistance have not been well elucidated. Methods: An epigenetics compound library containing 181 compounds was used to screen inhibitors possessing a prior synergistic effect with bortezomib (BTZ) in vitro. Molecular biology techniques were applied to uncover underlying mechanisms. Transcriptome profile assay was performed by RNA‐seq. NSG mouse‐based xenograft model and intra‐bone model were applied to qualify the synergistic effect in vivo. Results: We identified an Aurora kinase A inhibitor (MLN8237) possessed a significant synergistic effect with BTZ on t(4;14) positive MM cells. Aurora A protein level positively correlated with NSD2 level, and gain‐ and loss‐of‐functions of Aurora A correspondingly altered NSD2 protein and H3K36me2 levels. Mechanistically, Aurora A phosphorylated NSD2 at S56 residue to protect the protein from cleavage and degradation, thus methylation of Aurora A and phosphorylation of NSD2 bilaterally formed a positive regulating loop. Transcriptome profile assay of MM cells with AURKA depletion identified IL6R, STC2 and TCEA2 as the downstream target genes responsible for BTZ‐resistance (BR). Clinically, higher expressions of these genes correlated with poorer outcomes of MM patients. Combined administration of MLN8237 and BTZ significantly suppressed tumour growth in LP‐1 cells derived xenografts, and remarkably alleviated bone lesion in femurs of NSG mice. Conclusions: Aurora A phosphorylates NSD2 at S56 residue to enhance NSD2 methyltransferase activity and form a positive regulating loop in promoting MM chemoresistance, thus pharmacologically targeting Aurora A sensitizes t(4;14) positive MM to the proteasome inhibitors treatment. Our study uncovers a previously unknown reason of MM patients with t(4;14) engendering chemoresistance, and provides a theoretical basis for developing new treatment strategy for MM patients with different genomic backgrounds. [ABSTRACT FROM AUTHOR]
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- 2022
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13. Comparison of glycation and glycosylation level between bovine milk-based and goat milk-based infant formula through label-free proteomics techniques.
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Han, Hongyang, Pei, Jingjing, Feng, Jianhui, Yao, Huifang, Han, Binsong, Hou, Yanmei, Xie, Kui, Zhong, Jinjing, Zhang, Lina, Hettinga, Kasper, and Zhou, Peng
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PROTEOMICS ,WHEY proteins ,MAILLARD reaction ,SERUM albumin ,NATURAL immunity ,POST-translational modification ,INFANT formulas - Abstract
Heat treatment is unavoidable in the processing of infant formula; however, heat treatment causes the proteins to undergo Maillard reaction and form glycation products, which can negatively affect the nutrition and function of the protein. At the same time, glycosylation is a broad post-translational protein modification that is important in a variety of biological processes. However, glycated proteins as well as N-glycoprotein components in infant formula have not been well characterized. Here, a comprehensive comparative analysis of the glycated proteome as well as the N-glycosylated proteome was conducted in both bovine milk-based (BF) and goat milk-based (GF) infant formula. In total, 918 whey proteins were identified from the whey fraction, including 200 glycated proteins and 219 glycosylated proteins. Furthermore, 33 N-glycosylated proteins containing 101 N-glycosylation sites and 64 glycosylated peptides derived from 30 proteins were significantly different (p < 0.05) between BF and GF. Most of the significantly different proteins are associated with innate immunity as well as defense responses. With respect to the differences between BF and GF, ɑ-lactalbumin (LALBA) had higher glycation level in BF than GF; whereas β-lactoglobulin (LGB) had higher glycation level in GF than BF. For glycosylation level, transferin (TF) was highly glycosylated in GF than BF; while serum albumin (ALB) was highly glycosylated in BF than GF. Our results elucidated the proteome, glycated proteome, N-glycosylated proteome in bovine milk-based and goat milk-based infant formulas, which may be useful to researchers in related fields and provide guidance on the improvement of processing technology for infant formula. [ABSTRACT FROM AUTHOR]
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- 2024
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14. Exploitation of the Host Ubiquitin System: Means by Legionella pneumophila.
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Luo, Jingjing, Wang, Lidong, Song, Lei, and Luo, Zhao-Qing
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LEGIONELLA pneumophila ,UBIQUITIN ,POST-translational modification ,HOSTS (Biology) ,IMMUNE response - Abstract
Ubiquitination is a commonly used post-translational modification (PTM) in eukaryotic cells, which regulates a wide variety of cellular processes, such as differentiation, apoptosis, cell cycle, and immunity. Because of its essential role in immunity, the ubiquitin network is a common target of infectious agents, which have evolved various effective strategies to hijack and co-opt ubiquitin signaling for their benefit. The intracellular pathogen Legionella pneumophila represents one such example; it utilizes a large cohort of virulence factors called effectors to modulate diverse cellular processes, resulting in the formation a compartment called the Legionella-containing vacuole (LCV) that supports its replication. Many of these effectors function to re-orchestrate ubiquitin signaling with distinct biochemical activities. In this review, we highlight recent progress in the mechanism of action of L. pneumophila effectors involved in ubiquitination and discuss their roles in bacterial virulence and host cell biology. [ABSTRACT FROM AUTHOR]
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- 2021
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15. Thyroid hormone receptor alpha sumoylation modulates white adipose tissue stores.
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Liu, Yan-Yun, Jiang, Jingjing, Ke, Sujie, Milanesi, Anna, Abe, Kiyomi, Gastelum, Gilberto, Li, Jianrong, and Brent, Gregory A.
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THYROID hormone receptors , *WHITE adipose tissue , *HIGH-fat diet , *ADIPOSE tissues , *POST-translational modification , *FAT cells , *CARRIER proteins , *ADIPOSE tissue physiology - Abstract
Thyroid hormone (TH) and thyroid hormone receptor (THR) regulate stem cell proliferation and differentiation during development, as well as during tissue renewal and repair in the adult. THR undergoes posttranslational modification by small ubiquitin-like modifier (SUMO). We generated the THRA (K283Q/K288R)−/− mouse model for in vivo studies and used human primary preadipocytes expressing the THRA sumoylation mutant (K283R/K288R) and isolated preadipocytes from mutant mice for in vitro studies. THRA mutant mice had reduced white adipose stores and reduced adipocyte cell diameter on a chow diet, compared to wild-type, and these differences were further enhanced after a high fat diet. Reduced preadipocyte proliferation in mutant mice, compared to wt, was shown after in vivo labeling of preadipocytes with EdU and in preadipocytes isolated from mice fat stores and studied in vitro. Mice with the desumoylated THRA had disruptions in cell cycle G1/S transition and this was associated with a reduction in the availability of cyclin D2 and cyclin-dependent kinase 2. The genes coding for cyclin D1, cyclin D2, cyclin-dependent kinase 2 and Culin3 are stimulated by cAMP Response Element Binding Protein (CREB) and contain CREB Response Elements (CREs) in their regulatory regions. We demonstrate, by Chromatin Immunoprecipitation (ChIP) assay, that in mice with the THRA K283Q/K288R mutant there was reduced CREB binding to the CRE. Mice with a THRA sumoylation mutant had reduced fat stores on chow and high fat diets and reduced adipocyte diameter. [ABSTRACT FROM AUTHOR]
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- 2021
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16. Mck1 defines a key S-phase checkpoint effector in response to various degrees of replication threats
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Jingjing Zhang, Xiaojing Liu, Qinhong Cao, Li-Lin Du, Yanling Niu, Beidong Liu, Zhen Li, Jiaxin Zhang, Wenya Hou, Huiqiang Lou, Xuejiao Jin, Jiani Li, Sushma Sharma, and Xiaoli Li
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Cancer Research ,Cell- och molekylärbiologi ,Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy) ,Synthesis Phase ,Gene Expression ,Cell Cycle Proteins ,Yeast and Fungal Models ,QH426-470 ,Biochemistry ,Gene Knockout Techniques ,Glycogen Synthase Kinase 3 ,0302 clinical medicine ,Transcription (biology) ,Gene Expression Regulation, Fungal ,Transcriptional regulation ,Hydroxyurea ,Cell Cycle and Cell Division ,Post-Translational Modification ,Phosphorylation ,Promoter Regions, Genetic ,Genetics (clinical) ,Cellular Stress Responses ,Regulation of gene expression ,0303 health sciences ,Nucleotides ,Effector ,Transcriptional Control ,Messenger RNA ,Eukaryota ,In Vitro Kinase Assay ,Cell biology ,Nucleic acids ,Ribonucleotide reductase ,Bioassays and Physiological Analysis ,Experimental Organism Systems ,Cell Processes ,S Phase Cell Cycle Checkpoints ,Perspective ,Saccharomyces Cerevisiae ,Research Article ,DNA Replication ,Saccharomyces cerevisiae Proteins ,DNA damage ,Repressor ,Protein Serine-Threonine Kinases ,Biology ,Research and Analysis Methods ,03 medical and health sciences ,Saccharomyces ,Model Organisms ,Ribonucleotide Reductases ,Genetics ,Gene Regulation ,Molecular Biology ,Medicinsk bioteknologi (med inriktning mot cellbiologi (inklusive stamcellsbiologi), molekylärbiologi, mikrobiologi, biokemi eller biofarmaci) ,Ecology, Evolution, Behavior and Systematics ,030304 developmental biology ,Enzyme Assays ,Biology and life sciences ,Organisms ,Fungi ,Proteins ,Promoter ,DNA ,Cell Biology ,Ribonucleotides ,Yeast ,Repressor Proteins ,Animal Studies ,RNA ,Biochemical Analysis ,030217 neurology & neurosurgery ,Cell and Molecular Biology - Abstract
The S-phase checkpoint plays an essential role in regulation of the ribonucleotide reductase (RNR) activity to maintain the dNTP pools. How eukaryotic cells respond appropriately to different levels of replication threats remains elusive. Here, we have identified that a conserved GSK-3 kinase Mck1 cooperates with Dun1 in regulating this process. Deleting MCK1 sensitizes dun1Δ to hydroxyurea (HU) reminiscent of mec1Δ or rad53Δ. While Mck1 is downstream of Rad53, it does not participate in the post-translational regulation of RNR as Dun1 does. Mck1 phosphorylates and releases the Crt1 repressor from the promoters of DNA damage-inducible genes as RNR2-4 and HUG1. Hug1, an Rnr2 inhibitor normally silenced, is induced as a counterweight to excessive RNR. When cells suffer a more severe threat, Mck1 inhibits HUG1 transcription. Consistently, only a combined deletion of HUG1 and CRT1, confers a dramatic boost of dNTP levels and the survival of mck1Δdun1Δ or mec1Δ cells assaulted by a lethal dose of HU. These findings reveal the division-of-labor between Mck1 and Dun1 at the S-phase checkpoint pathway to fine-tune dNTP homeostasis., Author summary The appropriate amount and balance of four dNTPs are crucial for all cells correctly copying and passing on their genetic material generation by generation. Eukaryotes have developed an alert and response system to deal with the disturbance. Here, we uncovered a second-level effector branch. It is activated by the upstream surveillance kinase cascade, which can induce the expression of dNTP-producing enzymes. It can also reduce the inhibitor of these enzymes to further boost their activity according to the degrees of threats. These findings suggest a multi-level response system to guarantee the appropriate dNTP supply, which is essential to maintain genetic stability under various environmental challenges.
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- 2019
17. Extracellular carriers control lipid-dependent secretion, delivery, and activity of WNT morphogens.
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de Almeida Magalhaes, Taciani, Liu, Jingjing, Chan, Charlene, Borges, Kleiton Silva, Zhang, Jiuchun, Kane, Andrew J., Wierbowski, Bradley M., Ge, Yunhui, Liu, Zhiwen, Mannam, Prabhath, Zeve, Daniel, Weiss, Ron, Breault, David T., Huang, Pengxiang, and Salic, Adrian
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MEMBRANE transport proteins , *CARRIER proteins , *MEMBRANE proteins , *SECRETION , *GLYPICANS , *WNT signal transduction , *POST-translational modification - Abstract
WNT morphogens trigger signaling pathways fundamental for embryogenesis, regeneration, and cancer. WNTs are modified with palmitoleate, which is critical for binding Frizzled (FZD) receptors and activating signaling. However, it is unknown how WNTs are released and spread from cells, given their strong lipid-dependent membrane attachment. We demonstrate that secreted FZD-related proteins and WNT inhibitory factor 1 are WNT carriers, potently releasing lipidated WNTs and forming active soluble complexes. WNT release occurs by direct handoff from the membrane protein WNTLESS to the carriers. In turn, carriers donate WNTs to glypicans and FZDs involved in WNT reception and to the NOTUM hydrolase, which antagonizes WNTs by lipid moiety removal. WNT transfer from carriers to FZDs is greatly facilitated by glypicans that serve as essential co-receptors in Wnt signaling. Thus, an extracellular network of carriers dynamically controls secretion, posttranslational regulation, and delivery of WNT morphogens, with important practical implications for regenerative medicine. [Display omitted] • Lipid-modified WNTs are released from cells in complex with SFRP and WIF1 carriers • WNT carrier complexes are soluble and active in signaling • WNT transfer from carriers to FZD receptors is facilitated by glypican co-receptors • Some carriers transfer WNTs to the WNT-antagonizing lipid hydrolase NOTUM de Almeida Magalhaes et al. demonstrate that lipidated WNT morphogens are secreted by handoff from the membrane protein WLS to extracellular carrier proteins. Soluble WNT carrier complexes deliver WNTs to target cells or the inhibitory NOTUM hydrolase. These mechanisms explain how WNTs spread extracellularly to activate signaling in faraway cells. [ABSTRACT FROM AUTHOR]
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- 2024
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18. Propofol prevents human umbilical vein endothelial cell injury from Ang II-induced apoptosis by activating the ACE2-(1-7)-Mas axis and eNOS phosphorylation
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Liangqing Zhang, Du Feng, Jingjing Wang, Yue Yang, Jiuqing Liang, Zhe Hu, Yue Lu, and Fan Deng
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0301 basic medicine ,lcsh:Medicine ,Apoptosis ,030204 cardiovascular system & hematology ,Pharmacology ,Proto-Oncogene Mas ,Biochemistry ,Umbilical vein ,Epithelium ,Receptors, G-Protein-Coupled ,chemistry.chemical_compound ,Oxidative Damage ,0302 clinical medicine ,Enos ,Animal Cells ,Medicine and Health Sciences ,Post-Translational Modification ,Phosphorylation ,Enzyme-Linked Immunoassays ,Receptor ,lcsh:Science ,Propofol ,Multidisciplinary ,biology ,Cell Death ,Chemistry ,Angiotensin II ,Neurochemistry ,Cell Processes ,Human umbilical vein endothelial cell ,Angiotensin-Converting Enzyme 2 ,Cellular Types ,Anatomy ,Neurochemicals ,hormones, hormone substitutes, and hormone antagonists ,Research Article ,Nitric Oxide Synthase Type III ,Peptidyl-Dipeptidase A ,Nitric Oxide ,Protective Agents ,Transfection ,Research and Analysis Methods ,Nitric oxide ,03 medical and health sciences ,Proto-Oncogene Proteins ,Renin–angiotensin system ,Human Umbilical Vein Endothelial Cells ,Animals ,Humans ,Molecular Biology Techniques ,Immunoassays ,Molecular Biology ,lcsh:R ,Biology and Life Sciences ,Proteins ,Endothelial Cells ,Epithelial Cells ,Cell Biology ,biology.organism_classification ,Oxidative Stress ,030104 developmental biology ,Biological Tissue ,Immunologic Techniques ,lcsh:Q ,Reactive Oxygen Species ,Neuroscience - Abstract
Angiotensin II (AngII), a vasoactive peptide that elevates arterial blood pressure and results in hypertension, has been reported to directly induce vascular endothelial cell apoptosis. Recent work has demonstrated that propofol pre-treatment attenuates angiotensin II-induced apoptosis in human coronary artery endothelial cells. However, the underlying mechanism remains largely unknown. Here, we investigated human umbilical vein endothelial cells (HUVECs) subjected to angiotensin II-induced apoptosis in the presence or absence of propofol treatment and found that angiotensin II-induced apoptosis was attenuated by propofol in a dose-dependent manner. Furthermore, ELISA assays demonstrated that the ratio of angiotensin (1-7) (Ang (1-7)) to Ang II was increased after propofol treatment. We examined the expression of ACE2, Ang (1-7) and Mas and found that the ACE2-Ang (1-7)-Mas axis was up-regulated by propofol, while ACE2 overexpression increased phosphorylated endothelial nitric oxide synthase (phosphorylated eNOS) expression and siACE2 resulted in the repression of endothelial nitric oxide synthase (eNOS) phosphorylation. In conclusion, our study revealed that propofol can inhibit endothelial cell apoptosis induced by Ang II by activating the ACE2-Ang (1-7)-Mas axis and further up-regulating the expression and phosphorylation of eNOS.
- Published
- 2018
19. Cul4-Ddb1 ubiquitin ligases facilitate DNA replication-coupled sister chromatid cohesion through regulation of cohesin acetyltransferase Esco2
- Author
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Meiqian Jiang, Haitao Sun, Qinhong Cao, Jiaxin Zhang, Jingjing Zhang, Huiqiang Lou, Siyu Xin, and Zhen Li
- Subjects
Cancer Research ,Chromosomal Proteins, Non-Histone ,Gene Expression ,Cell Cycle Proteins ,Biochemistry ,Ligases ,0302 clinical medicine ,Small interfering RNAs ,Post-Translational Modification ,Genetics (clinical) ,0303 health sciences ,Chromosome Biology ,Chemical Reactions ,Eukaryota ,Nuclear Proteins ,Acetylation ,Cullin Proteins ,Chromatin ,Enzymes ,Cell biology ,Nucleic acids ,DNA-Binding Proteins ,Establishment of sister chromatid cohesion ,Chemistry ,Physical Sciences ,293T cells ,Cell lines ,Epigenetics ,Chromatid ,Biological cultures ,Research Article ,DNA Replication ,lcsh:QH426-470 ,Chromatids ,Biology ,Chromosomes ,Cell Line ,ESCO2 ,03 medical and health sciences ,DDB1 ,Acetyltransferases ,Genetics ,Humans ,Non-coding RNA ,Molecular Biology ,Ecology, Evolution, Behavior and Systematics ,030304 developmental biology ,Cohesin ,Ubiquitin ,Organisms ,Fungi ,DNA replication ,Biology and Life Sciences ,Proteins ,Cell Biology ,DNA ,Yeast ,Gene regulation ,Proliferating cell nuclear antigen ,Research and analysis methods ,lcsh:Genetics ,HEK293 Cells ,Enzymology ,biology.protein ,RNA ,030217 neurology & neurosurgery - Abstract
Cohesin acetyltransferases ESCO1 and ESCO2 play a vital role in establishing sister chromatid cohesion. How ESCO1 and ESCO2 are controlled in a DNA replication-coupled manner remains unclear in higher eukaryotes. Here we show a critical role of CUL4-RING ligases (CRL4s) in cohesion establishment via regulating ESCO2 in human cells. Depletion of CUL4A, CUL4B or DDB1 subunits substantially reduces the normal cohesion efficiency. We also show that MMS22L, a vertebrate ortholog of yeast Mms22, is one of DDB1 and CUL4-associated factors (DCAFs) involved in cohesion. Several lines of evidence show selective interaction of CRL4s with ESCO2 through LxG motif, which is lost in ESCO1. Depletion of either CRL4s or ESCO2 causes a defect in SMC3 acetylation, which can be rescued by HDAC8 inhibition. More importantly, both CRL4s and PCNA act as mediators for efficiently stabilizing ESCO2 on chromatin and catalyzing SMC3 acetylation. Taken together, we propose an evolutionarily conserved mechanism in which CRL4s and PCNA promote ESCO2-dependent establishment of sister chromatid cohesion., Author summary During the cycle of cell division and proliferation, each chromosome is copied into twin sister chromatids. To make sure a complete set of chromosomes are correctly passed on from generation to generation, the twins must be tethered together by a multi-protein ring called cohesin. ESCO1 and ESCO2 have been known to catalyze the acetylation of a cohesin subunit SMC3, which triggers the establishment of sister chromatid cohesion. Here, we have shown that CUL4-DDB1 ubiquitin ligases (CRL4MMS22L), in collaboration with PCNA, promote this key reaction. CRL4s selectively bind and stabilize ESCO2 on chromatin through a particular motif, which is lost in its cousin ESCO1. This explains the functional divergence and division of labor between these two paralogs. Both CRL4MMS22L and PCNA are known components of the moving DNA replication machines. So, our results help us to understand how twin sister chromatids become cohesive concomitantly with chromosome duplication process in human cells.
- Published
- 2019
20. A Systems Biology Approach Identifies Hidden Regulatory Connections Between the Circadian and Cell-Cycle Checkpoints.
- Author
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Zou, Xianlin, Kim, Dae Wook, Gotoh, Tetsuya, Liu, Jingjing, Kim, Jae Kyoung, and Finkielstein, Carla V.
- Subjects
SYSTEMS biology ,POST-translational modification ,CELL division ,CIRCADIAN rhythms ,CELL cycle - Abstract
Circadian rhythms form a self-sustaining, endogenous, time-keeping system that allows organisms to anticipate daily environmental changes. The core of the clock network consists of interlocking transcriptional-translational feedback loops that ensures that metabolic, behavioral, and physiological processes run on a 24 h timescale. The hierarchical nature of the clock manifests itself in multiple points of control on the daily cell division cycle, which relies on synthesis, degradation, and post-translational modification for progression. This relationship is particularly important for understanding the role of clock components in sensing stress conditions and triggering checkpoint signals that stop cell cycle progression. A case in point is the interplay among the circadian factor PERIOD2 (PER2), the tumor suppressor p53, and the oncogenic mouse double minute-2 homolog protein (MDM2), which is the p53's negative regulator. Under unstressed conditions, PER2 and p53 form a stable complex in the cytosol and, along with MDM2, a trimeric complex in the nucleus. Association of PER2 to the C-terminus end of p53 prevents MDM2-mediated ubiquitylation and degradation of p53 as well as p53's transcriptional activation. Remarkably, when not bound to p53, PER2 acts as substrate for the E3-ligase activity of MDM2; thus, PER2 is degraded in a phosphorylation-independent fashion. Unexpectedly, the phase relationship between PER2 and p53 are opposite; however, a systematic modeling approach, inferred from the oscillatory time course data of PER2 and p53, aided in identifying additional regulatory scenarios that explained, a priori , seemingly conflicting experimental data. Therefore, we advocate for a combined experimental/mathematical approach to elucidating multilevel regulatory cellular processes. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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21. N-glycosylomic analysis provides new insight into the molecular mechanism of firmness of fish fillet.
- Author
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Tian, Jingjing, Ji, Mengmeng, Liu, Jie, Xia, Yun, Zhang, Kai, Li, Hongyan, Gong, Wangbao, Li, Zhifei, Xie, Wenping, Wang, Guangjun, Xie, Jun, and Yu, Ermeng
- Subjects
- *
FISH fillets , *POST-translational modification , *CTENOPHARYNGODON idella , *EXTRACELLULAR matrix , *PROTEIN expression - Abstract
• Feeding grass carp with faba bean conferred them with "crisp" muscle texture. • "Crisp" grass carp muscle is characterized by substantial protein N -glycosylation. • N -glycosylated proteins participate in myogenesis, muscle function, & ECM formation. • N -glycosylation regulation is independent with phosphorylation regulation and protein expression. • These findings lay a foundation for optimizing fish fillet texture & quality. Post-translational protein modification affects muscle physiochemistry. To understand the roles of N- glycosylation in this process, the muscle N- glycoproteomes of crisp grass carp (CGC) and ordinary grass carp (GC) were analyzed and compared. We identified 325 N- glycosylated sites with the NxT motif, classified 177 proteins, and identified 10 upregulated and 19 downregulated differentially glycosylated proteins (DGPs). Gene Ontology and Kyoto Encyclopedia of Genes and Genomes annotations revealed that these DGPs participate in myogenesis, extracellular matrix content formation, and muscle function. The DGPs partially accounted for the molecular mechanisms associated with the relatively smaller fiber diameter and higher collagen content observed in CGC. Though the DGPs diverged from the identified differentially phosphorylated proteins and differentially expressed proteins detected in previous study, they all shared similar metabolic and signaling pathways. Thus, they might independently alter fish muscle texture. Overall, the present study provides novel insights into the mechanisms underlying fillet quality. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
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22. SiRNA Targeting mTOR Effectively Prevents the Proliferation and Migration of Human Lens Epithelial Cells
- Author
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Yahui Xi, Hongling Liu, Guiming Zhang, Chunmei Zhang, Jingjing Liu, and Na Jin
- Subjects
0301 basic medicine ,lcsh:Medicine ,Artificial Gene Amplification and Extension ,mTORC1 ,mTORC2 ,Biochemistry ,Polymerase Chain Reaction ,0302 clinical medicine ,Cell Movement ,Medicine and Health Sciences ,Small interfering RNAs ,RNA, Small Interfering ,Post-Translational Modification ,Phosphorylation ,lcsh:Science ,Multidisciplinary ,TOR Serine-Threonine Kinases ,Ophthalmic Procedures ,Ribosomal Protein S6 Kinases, 70-kDa ,Cell migration ,Cataract Surgery ,Cell biology ,Nucleic acids ,Cell Motility ,Cell Processes ,030220 oncology & carcinogenesis ,Ribosomal protein s6 ,Research Article ,Epithelial-Mesenchymal Transition ,Lens Capsule, Crystalline ,P70-S6 Kinase 1 ,Surgical and Invasive Medical Procedures ,Cell Migration ,Biology ,Mechanistic Target of Rapamycin Complex 1 ,Transfection ,Research and Analysis Methods ,Cell Growth ,Cell Line ,03 medical and health sciences ,Genetics ,Humans ,Molecular Biology Techniques ,Non-coding RNA ,Protein kinase B ,Molecular Biology ,PI3K/AKT/mTOR pathway ,Cell Proliferation ,Cell growth ,lcsh:R ,Biology and Life Sciences ,Proteins ,Epithelial Cells ,Cell Biology ,Capsule Opacification ,Gene regulation ,030104 developmental biology ,Gene Expression Regulation ,Multiprotein Complexes ,Cancer research ,RNA ,lcsh:Q ,sense organs ,Gene expression ,Proto-Oncogene Proteins c-akt ,Developmental Biology - Abstract
Posterior capsule opacification (PCO) is the most common complication that causes visual decrease after extracapsular cataract surgery. The primary cause of PCO formation is the proliferation of the residual lens epithelial cells (LECs). The mammalian target of rapamycin (mTOR) plays an important role in the growth and migration of LECs. In the current study, we used small interfering RNA (siRNA) to specifically attenuate mTOR in human lens epithelial B3 cells (HLE B3). We aimed to examine the effect of mTOR-siRNA on the proliferation, migration and epithelial-to-mesenchymal transition (EMT) of HLE B3 cells and explore the underlying mechanisms. The mTOR-siRNA was transfected into HLE B3 cells using lipofectamine 2000. The mRNA and protein levels of mTOR were examined to confirm the efficiency of mTOR-siRNA. The levels of mRNA and protein as well as the activity of mTOR down-stream effectors p70 ribosomal protein S6 kinase (p70S6K) and protein kinase B (PKB, AKT) were examined using real-time PCR or Western blot, respectively. The cell proliferation was determined using cell counting kit (CCK) 8 and cell growth curve assay. The cell migration was examined using Transwell system and Scratch assay. MTOR-siRNA effectively eliminated mTOR mRNA and protein. The proliferation and migration were significantly suppressed by mTOR-siRNA transfection. mTOR-siRNA reduced the mRNA of p70S6K and AKT in a time-dependent manner. Furthermore, the phosphorylation of p70S6K and AKT was decreased by mTOR-siRNA. MTOR-siRNA also eliminated the formation of mTORC1 and mTORC2 protein complex and blocked the transforming growth factor (TGF)-β-induced EMT. Our results suggested that mTOR-siRNA could effectively inhibit the proliferation, migration and EMT of HLE B3 cells through the inhibition of p70S6K and AKT. These results indicated that mTOR-siRNA might be an effective agent inhibiting HLE cells growth and EMT following cataract surgery and provide an alternative therapy for preventing PCO.
- Published
- 2016
23. Mck1 defines a key S-phase checkpoint effector in response to various degrees of replication threats.
- Author
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Li, Xiaoli, Jin, Xuejiao, Sharma, Sushma, Liu, Xiaojing, Zhang, Jiaxin, Niu, Yanling, Li, Jiani, Li, Zhen, Zhang, Jingjing, Cao, Qinhong, Hou, Wenya, Du, Li-Lin, Liu, Beidong, and Lou, Huiqiang
- Subjects
EUKARYOTIC cells ,RIBONUCLEOSIDE diphosphate reductase ,DNA replication ,CYTOLOGY ,LIFE sciences - Abstract
The S-phase checkpoint plays an essential role in regulation of the ribonucleotide reductase (RNR) activity to maintain the dNTP pools. How eukaryotic cells respond appropriately to different levels of replication threats remains elusive. Here, we have identified that a conserved GSK-3 kinase Mck1 cooperates with Dun1 in regulating this process. Deleting MCK1 sensitizes dun1Δ to hydroxyurea (HU) reminiscent of mec1Δ or rad53Δ. While Mck1 is downstream of Rad53, it does not participate in the post-translational regulation of RNR as Dun1 does. Mck1 phosphorylates and releases the Crt1 repressor from the promoters of DNA damage-inducible genes as RNR2-4 and HUG1. Hug1, an Rnr2 inhibitor normally silenced, is induced as a counterweight to excessive RNR. When cells suffer a more severe threat, Mck1 inhibits HUG1 transcription. Consistently, only a combined deletion of HUG1 and CRT1, confers a dramatic boost of dNTP levels and the survival of mck1Δdun1Δ or mec1Δ cells assaulted by a lethal dose of HU. These findings reveal the division-of-labor between Mck1 and Dun1 at the S-phase checkpoint pathway to fine-tune dNTP homeostasis. [ABSTRACT FROM AUTHOR]
- Published
- 2019
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24. Cul4-Ddb1 ubiquitin ligases facilitate DNA replication-coupled sister chromatid cohesion through regulation of cohesin acetyltransferase Esco2.
- Author
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Sun, Haitao, Zhang, Jiaxin, Xin, Siyu, Jiang, Meiqian, Zhang, Jingjing, Li, Zhen, Cao, Qinhong, and Lou, Huiqiang
- Subjects
UBIQUITIN ligases ,DNA replication ,SISTER chromatid exchange ,EUKARYOTES ,ACETYLATION ,CHROMATIN ,CATALYSIS - Abstract
Cohesin acetyltransferases ESCO1 and ESCO2 play a vital role in establishing sister chromatid cohesion. How ESCO1 and ESCO2 are controlled in a DNA replication-coupled manner remains unclear in higher eukaryotes. Here we show a critical role of UL4-ING igases (CRL4s) in cohesion establishment via regulating ESCO2 in human cells. Depletion of CUL4A, CUL4B or DDB1 subunits substantially reduces the normal cohesion efficiency. We also show that MMS22L, a vertebrate ortholog of yeast Mms22, is one of DB1 and UL4-ssociated actors (DCAFs) involved in cohesion. Several lines of evidence show selective interaction of CRL4s with ESCO2 through LxG motif, which is lost in ESCO1. Depletion of either CRL4s or ESCO2 causes a defect in SMC3 acetylation, which can be rescued by HDAC8 inhibition. More importantly, both CRL4s and PCNA act as mediators for efficiently stabilizing ESCO2 on chromatin and catalyzing SMC3 acetylation. Taken together, we propose an evolutionarily conserved mechanism in which CRL4s and PCNA promote ESCO2-dependent establishment of sister chromatid cohesion. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
25. Propofol prevents human umbilical vein endothelial cell injury from Ang II-induced apoptosis by activating the ACE2-(1-7)-Mas axis and eNOS phosphorylation.
- Author
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Zhang, Liangqing, Wang, Jingjing, Liang, Jiuqing, Feng, Du, Deng, Fan, Yang, Yue, Lu, Yue, and Hu, Zhe
- Subjects
- *
UMBILICAL veins , *PROPOFOL , *ENDOTHELIAL cells , *APOPTOSIS , *PHOSPHORYLATION , *NITRIC-oxide synthases , *WOUNDS & injuries , *THERAPEUTICS - Abstract
Angiotensin II (AngII), a vasoactive peptide that elevates arterial blood pressure and results in hypertension, has been reported to directly induce vascular endothelial cell apoptosis. Recent work has demonstrated that propofol pre-treatment attenuates angiotensin II-induced apoptosis in human coronary artery endothelial cells. However, the underlying mechanism remains largely unknown. Here, we investigated human umbilical vein endothelial cells (HUVECs) subjected to angiotensin II-induced apoptosis in the presence or absence of propofol treatment and found that angiotensin II-induced apoptosis was attenuated by propofol in a dose-dependent manner. Furthermore, ELISA assays demonstrated that the ratio of angiotensin (1–7) (Ang (1–7)) to Ang II was increased after propofol treatment. We examined the expression of ACE2, Ang (1–7) and Mas and found that the ACE2-Ang (1–7)-Mas axis was up-regulated by propofol, while ACE2 overexpression increased phosphorylated endothelial nitric oxide synthase (phosphorylated eNOS) expression and siACE2 resulted in the repression of endothelial nitric oxide synthase (eNOS) phosphorylation. In conclusion, our study revealed that propofol can inhibit endothelial cell apoptosis induced by Ang II by activating the ACE2-Ang (1–7)-Mas axis and further up-regulating the expression and phosphorylation of eNOS. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
- View/download PDF
26. Pathways crossing mammalian and plant sulfenomic landscapes.
- Author
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Huang, Jingjing, Willems, Patrick, Van Breusegem, Frank, and Messens, Joris
- Subjects
- *
REACTIVE oxygen species , *HYDROGEN peroxide , *PLANT defenses , *SULFENIC acids , *POST-translational modification - Abstract
Abstract Reactive oxygen species (ROS) and especially hydrogen peroxide, are potent signaling molecules that activate cellular defense responses. Hydrogen peroxide can provoke reversible and irreversible oxidative posttranslational modifications on cysteine residues of proteins that act in diverse signaling circuits. The initial oxidation product of cysteine, sulfenic acid, has emerged as a biologically relevant posttranslational modification, because it is the primary sulfur oxygen modification that precedes divergent series of additional adaptations. In this review, we focus on the functional consequences of sulfenylation for both mammalian and plant proteins. Furthermore, we created compendia of sulfenylated proteins in human and plants based on mass spectrometry experiments, thereby defining the current plant and human sulfenomes. To assess the evolutionary conservation of sulfenylation, the sulfenomes of human and plants were compared based on protein homology. In total, 185 human sulfenylated proteins showed homology to sulfenylated plant proteins and the conserved sulfenylation targets participated in specific biological pathways and metabolic processes. Comprehensive functional studies of sulfenylation remains a future challenge, with multiple candidates suggested by mass spectrometry awaiting scrutinization. Graphical abstract fx1 Highlights • Functional consequences of sulfenylation for mammalian and plant proteins. • Overview of proteomic studies to identify the sulfenome. • Updated list of human and plant proteins affected by sulfenylation. • Evolutionary comparison between human and plant sulfenylated proteins. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
- View/download PDF
27. E3 Ubiquitin Ligase RLIM Negatively Regulates c-Myc Transcriptional Activity and Restrains Cell Proliferation
- Author
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Long Yu, Lan Wang, Jingjing Zhu, Hao Cai, and Rui Gao
- Subjects
0301 basic medicine ,Small interfering RNA ,Molecular biology ,lcsh:Medicine ,Biochemistry ,law.invention ,Ubiquitin ,law ,Small interfering RNAs ,Post-Translational Modification ,Phosphorylation ,lcsh:Science ,Multidisciplinary ,Precipitation Techniques ,Ubiquitin ligase ,Cell biology ,Nucleic acids ,Cell Processes ,293T cells ,Cell lines ,Biological cultures ,Research Article ,Immunoprecipitation ,DNA construction ,Biology ,Transfection ,Cell Growth ,03 medical and health sciences ,Genetics ,Non-coding RNA ,Biology and life sciences ,Cell growth ,lcsh:R ,HEK 293 cells ,Ubiquitination ,Proteins ,Cell Biology ,Gene regulation ,Research and analysis methods ,Molecular biology techniques ,030104 developmental biology ,Plasmid Construction ,biology.protein ,Cancer research ,RNA ,Suppressor ,lcsh:Q ,Gene expression - Abstract
RNF12/RLIM is a RING domain-containing E3 ubiquitin ligase whose function has only begun to be elucidated recently. Although RLIM was reported to play important roles in some biological processes such as imprinted X-chromosome inactivation and regulation of TGF-β pathway etc., other functions of RLIM are largely unknown. Here, we identified RLIM as a novel E3 ubiquitin ligase for c-Myc, one of the most frequently deregulated oncoproteins in human cancers. RLIM associates with c-Myc in vivo and in vitro independently of the E3 ligase activity of RLIM. Moreover, RLIM promotes the polyubiquitination of c-Myc protein independently of Ser62 and Thr58 phosphorylation of c-Myc. However, RLIM-mediated ubiquitination does not affect c-Myc stability. Instead, RLIM inhibits the transcriptional activity of c-Myc through which RLIM restrains cell proliferation. Our results suggest that RLIM may function as a tumor suppressor by controlling the activity of c-Myc oncoprotein.
- Published
- 2016
28. Histone Deacetylase Inhibitors Trichostatin A and MCP30 Relieve Benzene-Induced Hematotoxicity via Restoring Topoisomerase IIα
- Author
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Kang Yu, Jiaqi Li, Shenghui Zhang, Yi Chen, Jingjing Chen, Zhouyi Zheng, Shanhu Qian, Yifen Shi, Lan Sun, and Yixiang Han
- Subjects
Cyclopropanes ,Male ,0301 basic medicine ,lcsh:Medicine ,Gene Expression ,Apoptosis ,Hydroxamic Acids ,Pathology and Laboratory Medicine ,Biochemistry ,Histones ,Mice ,0302 clinical medicine ,Animal Cells ,Medicine and Health Sciences ,Post-Translational Modification ,lcsh:Science ,Promoter Regions, Genetic ,Multidisciplinary ,Cell Death ,biology ,Organic Compounds ,Chromosome Biology ,Poisoning ,Chromatin Modification ,Chemical Reactions ,Acetylation ,Histone Modification ,Animal Models ,Chromatin ,DNA-Binding Proteins ,Chemistry ,Histone ,Cell Processes ,030220 oncology & carcinogenesis ,Physical Sciences ,Epigenetics ,Cellular Types ,Research Article ,medicine.drug ,Histone Acetylation ,Bone Marrow Cells ,Mouse Models ,Research and Analysis Methods ,Histone Deacetylases ,Histone H4 ,03 medical and health sciences ,Histone H3 ,Model Organisms ,Signs and Symptoms ,Antigens, Neoplasm ,Diagnostic Medicine ,Genetics ,medicine ,Animals ,Humans ,RNA, Messenger ,lcsh:R ,Organic Chemistry ,Chemical Compounds ,Biology and Life Sciences ,Proteins ,Benzene ,Cell Biology ,In vitro ,Histone Deacetylase Inhibitors ,DNA Topoisomerases, Type II ,030104 developmental biology ,Trichostatin A ,biology.protein ,Cancer research ,lcsh:Q ,Histone deacetylase - Abstract
Dysfunction of histone acetylation inhibits topoisomerase IIα (Topo IIα), which is implicated in benzene-induced hematotoxicity in patients with chronic benzene exposure. Whether histone deacetylase (HDAC) inhibitors can relieve benzene-induced hematotoxicity remains unclear. Here we showed that hydroquinone, a main metabolite of benzene, increased the HDAC activity, decreased the Topo IIα expression and induced apoptosis in human bone marrow mononuclear cells in vitro, and treatment with two HDAC inhibitors, namely trichostatin A (TSA) or a mixture of ribosome-inactivating proteins MCP30, almost completely reversed these effects. We further established a benzene poisoning murine model by inhaling benzene vapor in a container and found that benzene poisoning decreased the expression and activity of Topo IIα, and impaired acetylation of histone H4 and H3. The analysis of regulatory factors of Topo IIα promoter found that benzene poisoning decreased the mRNA levels of SP1 and C-MYB, and increased the mRNA level of SP3. Both TSA and MCP30 significantly enhanced the acetylation of histone H3 and H4 in Topo IIα promoter and increased the expression and activity of Topo IIα in benzene poisoning mice, which contributed to relieve the symptoms of hematotoxicity. Thus, treatment with HDAC inhibitors represents an attractive approach to reduce benzene-induced hematotoxicity.
- Published
- 2016
29. Pretreatment with Fucoidan from Fucus vesiculosus Protected against ConA-Induced Acute Liver Injury by Inhibiting Both Intrinsic and Extrinsic Apoptosis
- Author
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Jie Lu, Kan Chen, Yujing Xia, Chuanyong Guo, Jingjing Li, Sainan Li, Fan Wang, Tong Liu, and Yingqun Zhou
- Subjects
Male ,0301 basic medicine ,Physiology ,lcsh:Medicine ,Apoptosis ,Pharmacology ,Pathology and Laboratory Medicine ,Biochemistry ,White Blood Cells ,Mice ,chemistry.chemical_compound ,Animal Cells ,Immune Physiology ,Medicine and Health Sciences ,Concanavalin A ,Enzyme-Linked Immunoassays ,Post-Translational Modification ,Phosphorylation ,lcsh:Science ,Immune Response ,Innate Immune System ,Mice, Inbred BALB C ,Multidisciplinary ,Cell Death ,biology ,Fucoidan ,Cell Processes ,Cytokines ,Tumor necrosis factor alpha ,Cellular Types ,Chemical and Drug Induced Liver Injury ,Research Article ,Signal Transduction ,Immune Cells ,Immunology ,Fucus vesiculosus ,Caspase 3 ,Research and Analysis Methods ,Proinflammatory cytokine ,Necrosis ,03 medical and health sciences ,Signs and Symptoms ,Diagnostic Medicine ,Polysaccharides ,Animals ,Immunoassays ,Immunohistochemistry Techniques ,Inflammation ,Blood Cells ,Plant Extracts ,Macrophages ,lcsh:R ,Biology and Life Sciences ,Proteins ,Cell Biology ,Molecular Development ,biology.organism_classification ,TRADD ,Molecular biology ,Histochemistry and Cytochemistry Techniques ,030104 developmental biology ,chemistry ,Immune System ,Fucus ,Immunologic Techniques ,lcsh:Q ,Liver function ,Developmental Biology - Abstract
This study aimed to explore the effects of fucoidan from Fucus vesiculosus on concanavalin A (ConA)-induced acute liver injury in mice. Pretreatment with fucoidan protected liver function indicated by ALT, AST and histopathological changes by suppressing inflammatory cytokines, such as tumor necrosis factor alpha (TNF-α) and interferon gamma (IFN-γ). In addition, intrinsic and extrinsic apoptosis mediated by Bax, Bid, Bcl-2, Bcl-xL and Caspase 3, 8, and 9 were inhibited by fucoidan and the action was associated with the TRADD/TRAF2 and JAK2/STAT1 signal pathways. Our results demonstrated that fucoidan from Fucus vesiculosus alleviated ConA-induced acute liver injury via the inhibition of intrinsic and extrinsic apoptosis mediated by the TRADD/TRAF2 and JAK2/STAT1 pathways which were activated by TNF-α and IFN-γ. These findings could provide a potential powerful therapy for T cell-related hepatitis.
- Published
- 2016
30. SiRNA Targeting mTOR Effectively Prevents the Proliferation and Migration of Human Lens Epithelial Cells.
- Author
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Zhang, Chunmei, Liu, Jingjing, Jin, Na, Zhang, Guiming, Xi, Yahui, and Liu, Hongling
- Subjects
- *
SMALL interfering RNA , *MTOR protein , *EPITHELIAL cells , *CELL proliferation , *CELL migration , *CRYSTALLINE lens - Abstract
Posterior capsule opacification (PCO) is the most common complication that causes visual decrease after extracapsular cataract surgery. The primary cause of PCO formation is the proliferation of the residual lens epithelial cells (LECs). The mammalian target of rapamycin (mTOR) plays an important role in the growth and migration of LECs. In the current study, we used small interfering RNA (siRNA) to specifically attenuate mTOR in human lens epithelial B3 cells (HLE B3). We aimed to examine the effect of mTOR-siRNA on the proliferation, migration and epithelial-to-mesenchymal transition (EMT) of HLE B3 cells and explore the underlying mechanisms. The mTOR-siRNA was transfected into HLE B3 cells using lipofectamine 2000. The mRNA and protein levels of mTOR were examined to confirm the efficiency of mTOR-siRNA. The levels of mRNA and protein as well as the activity of mTOR down-stream effectors p70 ribosomal protein S6 kinase (p70S6K) and protein kinase B (PKB, AKT) were examined using real-time PCR or Western blot, respectively. The cell proliferation was determined using cell counting kit (CCK) 8 and cell growth curve assay. The cell migration was examined using Transwell system and Scratch assay. MTOR-siRNA effectively eliminated mTOR mRNA and protein. The proliferation and migration were significantly suppressed by mTOR-siRNA transfection. mTOR-siRNA reduced the mRNA of p70S6K and AKT in a time-dependent manner. Furthermore, the phosphorylation of p70S6K and AKT was decreased by mTOR-siRNA. MTOR-siRNA also eliminated the formation of mTORC1 and mTORC2 protein complex and blocked the transforming growth factor (TGF)-β-induced EMT. Our results suggested that mTOR-siRNA could effectively inhibit the proliferation, migration and EMT of HLE B3 cells through the inhibition of p70S6K and AKT. These results indicated that mTOR-siRNA might be an effective agent inhibiting HLE cells growth and EMT following cataract surgery and provide an alternative therapy for preventing PCO. [ABSTRACT FROM AUTHOR]
- Published
- 2016
- Full Text
- View/download PDF
31. E3 Ubiquitin Ligase RLIM Negatively Regulates c-Myc Transcriptional Activity and Restrains Cell Proliferation.
- Author
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Gao, Rui, Wang, Lan, Cai, Hao, Zhu, Jingjing, and Yu, Long
- Subjects
UBIQUITIN ligases ,GENETIC transcription ,X chromosome ,TRANSFORMING growth factors-beta ,ENZYME activation - Abstract
RNF12/RLIM is a RING domain-containing E3 ubiquitin ligase whose function has only begun to be elucidated recently. Although RLIM was reported to play important roles in some biological processes such as imprinted X-chromosome inactivation and regulation of TGF-β pathway etc., other functions of RLIM are largely unknown. Here, we identified RLIM as a novel E3 ubiquitin ligase for c-Myc, one of the most frequently deregulated oncoproteins in human cancers. RLIM associates with c-Myc in vivo and in vitro independently of the E3 ligase activity of RLIM. Moreover, RLIM promotes the polyubiquitination of c-Myc protein independently of Ser62 and Thr58 phosphorylation of c-Myc. However, RLIM-mediated ubiquitination does not affect c-Myc stability. Instead, RLIM inhibits the transcriptional activity of c-Myc through which RLIM restrains cell proliferation. Our results suggest that RLIM may function as a tumor suppressor by controlling the activity of c-Myc oncoprotein. [ABSTRACT FROM AUTHOR]
- Published
- 2016
- Full Text
- View/download PDF
32. Histone Deacetylase Inhibitors Trichostatin A and MCP30 Relieve Benzene-Induced Hematotoxicity via Restoring Topoisomerase IIα.
- Author
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Chen, Jingjing, Zheng, Zhouyi, Chen, Yi, Li, Jiaqi, Qian, Shanhu, Shi, Yifen, Sun, Lan, Han, Yixiang, Zhang, Shenghui, and Yu, Kang
- Subjects
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BLOOD testing , *HISTONE deacetylase inhibitors , *TRICHOSTATIN A , *DNA topoisomerase II , *BENZENE , *LABORATORY mice , *PHYSIOLOGY - Abstract
Dysfunction of histone acetylation inhibits topoisomerase IIα (Topo IIα), which is implicated in benzene-induced hematotoxicity in patients with chronic benzene exposure. Whether histone deacetylase (HDAC) inhibitors can relieve benzene-induced hematotoxicity remains unclear. Here we showed that hydroquinone, a main metabolite of benzene, increased the HDAC activity, decreased the Topo IIα expression and induced apoptosis in human bone marrow mononuclear cells in vitro, and treatment with two HDAC inhibitors, namely trichostatin A (TSA) or a mixture of ribosome-inactivating proteins MCP30, almost completely reversed these effects. We further established a benzene poisoning murine model by inhaling benzene vapor in a container and found that benzene poisoning decreased the expression and activity of Topo IIα, and impaired acetylation of histone H4 and H3. The analysis of regulatory factors of Topo IIα promoter found that benzene poisoning decreased the mRNA levels of SP1 and C-MYB, and increased the mRNA level of SP3. Both TSA and MCP30 significantly enhanced the acetylation of histone H3 and H4 in Topo IIα promoter and increased the expression and activity of Topo IIα in benzene poisoning mice, which contributed to relieve the symptoms of hematotoxicity. Thus, treatment with HDAC inhibitors represents an attractive approach to reduce benzene-induced hematotoxicity. [ABSTRACT FROM AUTHOR]
- Published
- 2016
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33. Pretreatment with Fucoidan from Fucus vesiculosus Protected against ConA-Induced Acute Liver Injury by Inhibiting Both Intrinsic and Extrinsic Apoptosis.
- Author
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Li, Jingjing, Chen, Kan, Li, Sainan, Liu, Tong, Wang, Fan, Xia, Yujing, Lu, Jie, Zhou, Yingqun, and Guo, Chuanyong
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FUCUS vesiculosus , *APOPTOSIS , *THERAPEUTICS , *LIVER injuries , *HISTOPATHOLOGY , *STAT proteins - Abstract
This study aimed to explore the effects of fucoidan from Fucus vesiculosus on concanavalin A (ConA)-induced acute liver injury in mice. Pretreatment with fucoidan protected liver function indicated by ALT, AST and histopathological changes by suppressing inflammatory cytokines, such as tumor necrosis factor alpha (TNF-α) and interferon gamma (IFN-γ). In addition, intrinsic and extrinsic apoptosis mediated by Bax, Bid, Bcl-2, Bcl-xL and Caspase 3, 8, and 9 were inhibited by fucoidan and the action was associated with the TRADD/TRAF2 and JAK2/STAT1 signal pathways. Our results demonstrated that fucoidan from Fucus vesiculosus alleviated ConA-induced acute liver injury via the inhibition of intrinsic and extrinsic apoptosis mediated by the TRADD/TRAF2 and JAK2/STAT1 pathways which were activated by TNF-α and IFN-γ. These findings could provide a potential powerful therapy for T cell-related hepatitis. [ABSTRACT FROM AUTHOR]
- Published
- 2016
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- View/download PDF
34. Cysteines under ROS attack in plants: a proteomics view.
- Author
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Akter, Salma, Jingjing Huang, Waszczak, Cezary, Jacques, Silke, Gevaert, Kris, Van Breusegem, Frank, and Messens, Joris
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CYSTEINE , *REACTIVE oxygen species , *PROTEOMICS , *POST-translational modification , *SULFENIC acids , *OXIDATIVE stress , *PLANTS , *GLUTATHIONE - Abstract
Plants generate reactive oxygen species (ROS) as part of their metabolism and in response to various external stress factors, potentially causing significant damage to biomolecules and cell structures. During the course of evolution, plants have adapted to ROS toxicity, and use ROS as signalling messengers that activate defence responses. Cysteine (Cys) residues in proteins are one of the most sensitive targets for ROS-mediated posttranslational modifications, and they have become key residues for ROS signalling studies. The reactivity of Cys residues towards ROS, and their ability to react to different oxidation states, allow them to appear at the crossroads of highly dynamic oxidative events. As such, a redox-active cysteine can be present as S-glutathionylated (-SSG), disulfide bonded (S-S), sulfenylated (-SOH), sulfinylated (-SO2H), and sulfonylated (-SO3H). The sulfenic acid (-SOH) form has been considered as part of ROS-sensing pathways, as it leads to further modifications which affect protein structure and function. Redox proteomic studies are required to understand how and why cysteines undergo oxidative post-translational modifications and to identify the ROS-sensor proteins. Here, we update current knowledge of cysteine reactivity with ROS. Further, we give an overview of proteomic techniques that have been applied to identify different redox-modified cysteines in plants. There is a particular focus on the identification of sulfenylated proteins, which have the potential to be involved in plant signal transduction. [ABSTRACT FROM AUTHOR]
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- 2015
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35. Oxidative post-translational modifications of cysteine residues in plant signal transduction.
- Author
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Waszczak, Cezary, Akter, Salma, Jacques, Silke, Jingjing Huang, Messens, Joris, and Van Breusegem, Frank
- Subjects
POST-translational modification ,PLANTS ,OXIDATIVE stress ,CYSTEINE ,CELLULAR signal transduction ,OXYGEN in the body ,OXIDATION-reduction reaction ,PLANT hormones - Abstract
In plants, fluctuation of the redox balance by altered levels of reactive oxygen species (ROS) can affect many aspects of cellular physiology. ROS homeostasis is governed by a diversified set of antioxidant systems. Perturbation of this homeostasis leads to transient or permanent changes in the redox status and is exploited by plants in different stress signalling mechanisms. Understanding how plants sense ROS and transduce these stimuli into downstream biological responses is still a major challenge. ROS can provoke reversible and irreversible modifications to proteins that act in diverse signalling pathways. These oxidative post-translational modifications (Ox-PTMs) lead to oxidative damage and/or trigger structural alterations in these target proteins. Characterization of the effect of individual Ox-PTMs on individual proteins is the key to a better understanding of how cells interpret the oxidative signals that arise from developmental cues and stress conditions. This review focuses on ROS-mediated Ox-PTMs on cysteine (Cys) residues. The Cys side chain, with its high nucleophilic capacity, appears to be the principle target of ROS. Ox-PTMs on Cys residues participate in various signalling cascades initiated by plant stress hormones. We review the mechanistic aspects and functional consequences of Cys Ox-PTMs on specific target proteins in view of stress signalling events. [ABSTRACT FROM AUTHOR]
- Published
- 2015
- Full Text
- View/download PDF
36. UFMylation: An integral post-translational modification for the regulation of proteostasis and cellular functions.
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Wang, Xiaohui, Lv, Xiaowei, Ma, Jingjing, and Xu, Guoqiang
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PROTEOLYSIS , *CELL physiology , *POST-translational modification , *DNA repair , *DRUG discovery , *BIOCHEMICAL substrates , *GENETIC transcription - Abstract
Ubiquitin-fold modifier 1 (UFM1) is covalently conjugated to protein substrates via a cascade of enzymatic reactions, a process known as UFMylation. UFMylation orchestrates an array of vital biological functions, including maintaining endoplasmic reticulum (ER) homeostasis, facilitating protein biogenesis, promoting cellular differentiation, regulating DNA damage response, and participating in cancer-associated signaling pathways. UFMylation has rapidly evolved into one of the forefront research areas within the last few years, yet much remains to be uncovered. In this review, first, UFMylation and its cellular functions associated with diseases are briefly introduced. Then, we summarize the proteomic approaches for identifying UFMylation substrates and explore the impact of UFMylation on gene transcription, protein translation, and maintenance of ER homeostasis. Next, we highlight the intricate regulation between UFMylation and two protein degradation pathways, the ubiquitin-proteasome system and the autophagy-lysosome pathway, and explore the potential of UFMylation system as a drug target. Finally, we discuss emerging perspectives in the UFMylation field. This review may provide valuable insights for drug discovery targeting the UFMylation system. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
37. A spatial vascular transcriptomic, proteomic, and phosphoproteomic atlas unveils an angiocrine Tie–Wnt signaling axis in the liver.
- Author
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Inverso, Donato, Shi, Jingjing, Lee, Ki Hong, Jakab, Moritz, Ben-Moshe, Shani, Kulkarni, Shubhada R., Schneider, Martin, Wang, Guanxiong, Komeili, Marziyeh, Vélez, Paula Argos, Riedel, Maria, Spegg, Carleen, Ruppert, Thomas, Schaeffer-Reiss, Christine, Helm, Dominic, Singh, Indrabahadur, Boutros, Michael, Chintharlapalli, Sudhakar, Heikenwalder, Mathias, and Itzkovitz, Shalev
- Subjects
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LIVER , *ENDOTHELIAL cells , *LIVER regeneration , *CELL analysis , *POST-translational modification , *VASCULAR smooth muscle , *LIVER cells - Abstract
Single-cell transcriptomics (scRNA-seq) has revolutionized the understanding of the spatial architecture of tissue structure and function. Advancing the "transcript-centric" view of scRNA-seq analyses is presently restricted by the limited resolution of proteomics and genome-wide techniques to analyze post-translational modifications. Here, by combining spatial cell sorting with transcriptomics and quantitative proteomics/phosphoproteomics, we established the spatially resolved proteome landscape of the liver endothelium, yielding deep mechanistic insight into zonated vascular signaling mechanisms. Phosphorylation of receptor tyrosine kinases was detected preferentially in the central vein area, resulting in an atypical enrichment of tyrosine phosphorylation. Prototypic biological validation identified Tie receptor signaling as a selective and specific regulator of vascular Wnt activity orchestrating angiocrine signaling, thereby controlling hepatocyte function during liver regeneration. Taken together, the study has yielded fundamental insight into the spatial organization of liver endothelial cell signaling. Spatial sorting may be employed as a universally adaptable strategy for multiomic analyses of scRNA-seq-defined cellular (sub)-populations. [Display omitted] • ScRNA-seq-guided spatial sort enables multiomic dissection of the liver vasculature • Liver sinusoidal endothelial cells have a hybrid vascular-lymphatic phenotype • Tyrosine phosphorylation of endothelial cell molecules is enriched on central vein • Endothelial Tie1 shapes hepatic Wnt signal zonation and promotes liver regeneration Inverso, Shi et al. generate a multiomic encyclopedia of liver endothelial cells (L-ECs) with spatial resolution of transcriptome, proteome, and phosphoproteome. The study provides insight into liver vascular zonation and a template for scRNA-seq-data-guided spatial proteome and phosphoproteome analyses. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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38. H2O2-dependent oxidation of the transcription factor GmNTL1 promotes salt tolerance in soybean.
- Author
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Zhang, Wenxiao, Zhi, Wenjiao, Qiao, Hong, Huang, Jingjing, Li, Shuo, Lu, Qing, Wang, Nan, Li, Qiang, Zhou, Qian, Sun, Jiaqi, Bai, Yuting, Zheng, Xiaojian, Bai, Mingyi, Van Breusegem, Frank, and Xiang, Fengning
- Subjects
- *
TRANSCRIPTION factors , *POST-translational modification , *GENE expression , *REACTIVE oxygen species , *SALT , *SOYBEAN - Abstract
Reactive oxygen species (ROS) play an essential role in plant growth and responses to environmental stresses. Plant cells sense and transduce ROS signaling directly via hydrogen peroxide (H2O2)–mediated posttranslational modifications (PTMs) on protein cysteine residues. Here, we show that the H2O2-mediated cysteine oxidation of NAC WITH TRANS-MEMBRANE MOTIF1-LIKE 1 (GmNTL1) in soybean (Glycine max) during salt stress promotes its release from the endoplasmic reticulum (ER) membrane and translocation to the nucleus. We further show that an oxidative posttranslational modification on GmNTL1 residue Cys-247 steers downstream amplification of ROS production by binding to and activating the promoters of RESPIRATORY BURST OXIDASE HOMOLOG B (GmRbohB) genes, thereby creating a feed-forward loop to fine-tune GmNTL1 activity. In addition, oxidation of GmNTL1 Cys-247 directly promotes the expression of CATION H+ EXCHANGER 1 (GmCHX1)/SALT TOLERANCE-ASSOCIATED GENE ON CHROMOSOME 3 (GmSALT3) and Na+/H+ Antiporter 1 (GmNHX1). Accordingly, transgenic overexpression of GmNTL1 in soybean increases the H2O2 levels and K+/Na+ ratio in the cell, promotes salt tolerance, and increases yield under salt stress, while an RNA interference–mediated knockdown of GmNTL1 elicits the opposite effects. Our results reveal that the salt-induced oxidation of GmNTL1 promotes its relocation and transcriptional activity through an H2O2-mediated posttranslational modification on cysteine that improves resilience of soybean against salt stress. Oxidation of transcription factor GmNTL1 triggers its translocation to the nucleus, where it activates the transcription of several target genes to regulate soybean (Glycine max) salt tolerance. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
39. S-acylation of p62 promotes p62 droplet recruitment into autophagosomes in mammalian autophagy.
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Huang, Xue, Yao, Jia, Liu, Lu, Chen, Jing, Mei, Ligang, Huangfu, Jingjing, Luo, Dong, Wang, Xinyi, Lin, Changhai, Chen, Xiaorong, Yang, Yi, Ouyang, Sheng, Wei, Fujing, Wang, Zhuolin, Zhang, Shaolin, Xiang, Tingxiu, Neculai, Dante, Sun, Qiming, Kong, Eryan, and Tate, Edward W.
- Subjects
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PROTEOLYSIS , *AUTOPHAGY , *POST-translational modification , *PROTEIN S , *MICROTUBULE-associated proteins , *COATED vesicles - Abstract
p62 is a well-characterized autophagy receptor that recognizes and sequesters specific cargoes into autophagosomes for degradation. p62 promotes the assembly and removal of ubiquitinated proteins by forming p62-liquid droplets. However, it remains unclear how autophagosomes efficiently sequester p62 droplets. Herein, we report that p62 undergoes reversible S -acylation in multiple human-, rat-, and mouse-derived cell lines, catalyzed by zinc-finger Asp-His-His-Cys S -acyltransferase 19 (ZDHHC19) and deacylated by acyl protein thioesterase 1 (APT1). S -acylation of p62 enhances the affinity of p62 for microtubule-associated protein 1 light chain 3 (LC3)-positive membranes and promotes autophagic membrane localization of p62 droplets, thereby leading to the production of small LC3-positive p62 droplets and efficient autophagic degradation of p62-cargo complexes. Specifically, increasing p62 acylation by upregulating ZDHHC19 or by genetic knockout of APT1 accelerates p62 degradation and p62-mediated autophagic clearance of ubiquitinated proteins. Thus, the protein S -acylation-deacylation cycle regulates p62 droplet recruitment to the autophagic membrane and selective autophagic flux, thereby contributing to the control of selective autophagic clearance of ubiquitinated proteins. [Display omitted] • S -acyltransferase ZDHHC19 catalyzes p62 S -acylation at Cys289 and Cys290 • S -acylation facilitates autophagic degradation of p62 and ubiquitinated proteins • S -acylation promotes autophagic membrane localization of p62 droplets • APT1 deacylates p62 and suppresses p62-mediated selective autophagy How autophagosomes efficiently sequester phase-separated p62 droplets remains unclear. Huang et al. found a posttranslational modification of p62 with long-chain fatty acids. p62 S -acylation regulates p62 droplet recruitment to the autophagic membrane and selective autophagic flux, thereby contributing to the control of selective autophagic clearance of ubiquitinated proteins. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
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