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179 results on '"Hao, Mingang"'

1. Light-activated mitochondrial fission through optogenetic control of mitochondria-lysosome contacts.

Author

Qiu, Kangqiang, Zou, Weiwei, Fang, Hongbao, Hao, Mingang, Mehta, Kritika, Tian, Zhiqi, Guan, Jun-Lin, Zhang, Kai, Huang, Taosheng, and Diao, Jiajie

Subjects
Lysosomes, Mitochondria, Humans, Mitochondrial Diseases, Phosphate Transport Proteins, Mitochondrial Proteins, Mitochondrial Dynamics, Optogenetics, Neurosciences, Generic health relevance
Abstract

Mitochondria are highly dynamic organelles whose fragmentation by fission is critical to their functional integrity and cellular homeostasis. Here, we develop a method via optogenetic control of mitochondria-lysosome contacts (MLCs) to induce mitochondrial fission with spatiotemporal accuracy. MLCs can be achieved by blue-light-induced association of mitochondria and lysosomes through various photoactivatable dimerizers. Real-time optogenetic induction of mitochondrial fission is tracked in living cells to measure the fission rate. The optogenetic method partially restores the mitochondrial functions of SLC25A46-/- cells, which display defects in mitochondrial fission and hyperfused mitochondria. The optogenetic MLCs system thus provides a platform for studying mitochondrial fission and treating mitochondrial diseases.

Published
2022

12. AZI2 mediates TBK1 activation at unresolved selective autophagy cargo receptor complexes with implications for CD8 T-cell infiltration in breast cancer.

Author

Yeo, Syn Kok, Haas, Michael, Manupati, Kanakaraju, Hao, Mingang, Yang, Fuchun, Chen, Song, and Guan, Jun-Lin

Subjects
BREAST cancer, IMMUNE checkpoint inhibitors, AUTOPHAGY, ADAPTOR proteins, CD8 antigen, INTERFERON receptors, DNA helicases
Abstract

Most breast cancers do not respond to immune checkpoint inhibitors and there is an urgent need to identify novel sensitization strategies. Herein, we uncovered that activation of the TBK-IFN pathway that is mediated by the TBK1 adapter protein AZI2 is a potent strategy for this purpose. Our initial observations showed that RB1CC1 depletion leads to accumulation of AZI2, in puncta along with selective macroautophagy/autophagy cargo receptors, which are both required for TBK1 activation. Specifically, disrupting the selective autophagy function of RB1CC1 was sufficient to sustain AZI2 puncta accumulation and TBK1 activation. AZI2 then mediates downstream activation of DDX3X, increasing its interaction with IRF3 for transcription of pro-inflammatory chemokines. Consequently, we performed a screen to identify inhibitors that can induce the AZI2-TBK1 pathway, and this revealed Lys05 as a pharmacological agent that induced pro-inflammatory chemokine expression and CD8+ T cell infiltration into tumors. Overall, we have identified a distinct AZI2-TBK1-IFN signaling pathway that is responsive to selective autophagy blockade and can be activated to make breast cancers more immunogenic. Abbreviations: AZI2/NAP1: 5-azacytidine induced 2; CALCOCO2: calcium binding and coiled-coil domain 2; DDX3X: DEAD-box helicase 3 X-linked; FCCP: carbonyl cyanide p-triflouromethoxyphenylhydrazone; a protonophore that depolarizes the mitochondrial inner membrane; ICI: immune checkpoint inhibitor; IFN: interferon; NBR1: NBR1 autophagy cargo receptor; OPTN: optineurin; RB1CC1/FIP200: RB1 inducible coiled-coil 1; SQSTM1/p62: sequestosome 1; TAX1BP1: Tax1 binding protein 1; TBK1: TANK binding kinase 1 [ABSTRACT FROM AUTHOR]

Published
2024
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14. HIC1 deletion promotes breast cancer progression by activating tumor cell/fibroblast crosstalk

Author

Wang, Yingying, Weng, Xiaoling, Wang, Luoyang, Hao, Mingang, Li, Yue, Hou, Lidan, Liang, Yu, Wu, Tianqi, Yao, Mengfei, Lin, Guowen, Jiang, Yiwei, Fu, Guohui, Hou, Zhaoyuan, Meng, Xiangjun, Lu, Jinsong, and Wang, Jianhua

Subjects
Breast cancer -- Development and progression -- Diagnosis -- Care and treatment -- Patient outcomes, Fibroblasts -- Research, Stem cells, Tumors, Women's health, Health, Health care industry
Abstract

Breast cancer (BrCa) is the malignant tumor that most seriously threatens female health; however, the molecular mechanism underlying its progression remains unclear. Here, we found that conditional deletion of hypermethylated in cancer 1 (HIC1) in the mouse mammary gland might contribute to premalignant transformation in the early stage of tumor formation. Moreover, the chemokine (C-X-C motif) ligand 14 (CXCL14) secreted by HIC1-deleted BrCa cells bound to its cognate receptor GPR85 on mammary fibroblasts in the microenvironment and was responsible for activating these fibroblasts via the ERK1/2, Akt, and neddylation pathways, whereas the activated fibroblasts promoted BrCa progression via the induction of epithelial-mesenchymal transition (EMT) by the C-C chemokine ligand 17 (CCL17)/CC chemokine receptor 4 (CCR4) axis. Finally, we confirmed that the HIC1-CXCL14-CCL17 loop was associated with the malignant progression of BrCa. Therefore, the crosstalk between HIC1-deleted BrCa cells and mammary fibroblasts might play a critical role in BrCa development. Exploring the progression of BrCa from the perspective of microenvironment will be beneficial for identifying the potential prognostic markers of breast tumor and providing more effective treatment strategies., IntroductionBreast cancer (BrCa) is the most frequently diagnosed malignant tumor in women worldwide and represents the main cause of cancer-related death (1). Although systematic therapeutic approaches have decreased cancer-specific mortality, [...]

Published
2018
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16. Ultra‐long‐distance transport of aeolian sand: The provenance of an intermontane desert, south‐east China.

Author

Cao, Shuo, Zhang, Laiming, Mountney, Nigel P., Ma, Jing, Hao, Mingang, and Wang, Chengshan

Subjects
DESERTS, SAND, SEDIMENT transport, ARID regions, GLOBAL warming, SANDSTORMS, WESTERLIES
Abstract

Intermontane deserts are an important type of arid‐climate sedimentary system. Although rare at present, the sedimentary records of intermontane deserts reveal their widespread development in past greenhouse periods, and they might develop in the near future in response to ongoing global warming. Determination of the provenance of sand supplied for the construction of intermontane deserts is important to gain improved understanding of the potential impact of future climate on environmental evolution in arid and semi‐arid regions. During the Cretaceous, a typical intermontane desert developed in the Xinjiang Basin, south‐east China. In this study, the origin, spatial variability, and transport pathways of both aeolian and alluvial–fluvial sediments in the Xinjiang intermontane desert are investigated by analyses of bulk‐rock petrography and detrital‐zircon U–Pb geochronology. These results demonstrate that the sand in the Xinjiang intermontane desert succession was mainly of extraneous origin and wind‐derived. The nearby South China Block and South China Magmatic Belt were primary sources, and the 1000 km distant western margin of Yangtze Block was an important secondary source. During the Late Cretaceous, the westerlies were stronger in the northern than in the southern hemisphere with doubled wind speeds. In such a climatic context, the results herein suggest that the ultra‐long‐distance aeolian sediment transport was likely further enabled by two factors: (i) the strengthening of intermittent westerly winds during short‐lived glacial episodes; and (ii) the presence of a low‐relief corridor that served as a transport pathway from source to sink. [ABSTRACT FROM AUTHOR]

Published
2023
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50. Regulation of RB1CC1/FIP200 stability and autophagy function by CREBBP-mediated acetylation in an intrinsically disordered region.

Author

Yi, Fei, Cai, Chunmiao, Ruan, Banzhan, Hao, Mingang, Yeo, Syn Kok, Haas, Michael, Yang, Fuchun, Zhang, Xiaoting, and Guan, Jun-Lin

Subjects
ACETYLATION, AUTOPHAGY, UBIQUITINATION, CREB protein, CARRIER proteins, POST-translational modification, NICOTINAMIDE
Abstract

RB1CC1/FIP200 is an essential macroautophagy/autophagy protein that plays an important role in a variety of biological and disease processes through its canonical autophagy-dependent and -independent functions. However, it remains largely unknown whether post-translational modifications could regulate RB1CC1 and its associated autophagy functions. Here, we report acetylation of several lysine residues of RB1CC1 by acetyltransferase CREBBP (CREB binding protein), with K276 as the major CREBBP acetylation site. K276 is also identified as a ubiquitination site by mass spectrometry, and acetylation at this site reduces ubiquitination of RB1CC1 to inhibit its ubiquitin-dependent degradation. We also find that RB1CC1 contains an N-terminal intrinsically disordered region (IDR) capable of forming liquid-liquid phase separation (LLPS) in vitro, which may drive formation of RB1CC1 puncta with LLPS properties in cells independent of SQSTM1/p62 and other autophagy receptors CALCOCO2/NDP52, NBR1, TAX1BP1 and OPTN. Mutational analysis shows that both K276 acetylation and the N-terminal IDR containing it are important for maintaining canonical autophagy function of RB1CC1 in breast cancer cells. Our findings demonstrate regulation of RB1CC1 by a new post-translational mechanism and suggest potential therapeutic application of inducing RB1CC1 degradation through blocking K276 acetylation in the treatment of cancer and other diseases. Abbreviations: Baf-A1: bafilomycin A1; CREBBP/CBP: CREB binding protein; CHX: cycloheximide; EP300/p300: E1A binding protein p300; FRAP: fluorescence recovery after photobleaching; HADCs: histone deacetylases; IDR: intrinsically disordered region; LLPS: liquid-liquid phase separation; KAT2A/GCN5: lysine acetyltransferase 2A; KAT2B/PCAF: lysine acetyltransferase 2B; KAT5/TIP60: lysine acetyltransferase 5; KAT8/MOF: lysine acetyltransferase 8; NAM: nicotinamide; PAS: phagophore assembly site; PEG-8000: polyethylene glycol 8000; RB1CC1/FIP200: RB1 inducible coiled-coil 1; TSA: trichostatin A. [ABSTRACT FROM AUTHOR]

Published
2023
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