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A myriad of abiotic stress responses in plants are controlled by abscisic acid (ABA) signaling. ABA receptors can be degraded by both the 26S proteasome pathway and vacuolar degradation pathway after processing via the endosomal sorting complex required for transport (ESCRT) proteins. Despite being essential for ABA signaling, the upstream regulators of ESCRTs remain unknown. Here, we report that the ESCRT-I component VPS23A is an unstable protein that is degraded via the ubiquitin-proteasome system (UPS). The UEV domain of VPS23A physically interacts with the two PSAP motifs of XBAT35, an E3 ubiquitin ligase, and this interaction results in the deposition of K48 polyubiquitin chains on VPS23A, marking it for degradation by 26S proteasomes. We showed that XBAT35 in plants is a positive regulator of ABA responses that acts via the VPS23A/PYL4 complex, specifically by accelerating VPS23A turnover and thereby increasing accumulation of the ABA receptor PYL4. This work deciphers how an ESCRT component is regulated in plants and deepens our understanding of plant stress responses by illustrating a mechanism whereby crosstalk between the UPS and endosome-vacuole-mediated degradation pathways controls ABA signaling. The ESCRT-I component VPS23A recognizes the ABA receptor PYL4 for endosome-vacuole-mediated degradation during ABA signaling. This study reveals that the E3 ubiquitin ligase XBAT35 accelerates VPS23A turnover through the 26S proteasome degradation pathway to maintain PYL4 protein homeostasis. This work illustrates a mechanism by which crosstalk between the ubiquitin-proteasome system and endosome-vacuole-mediated degradation pathways controls ABA signaling. [ABSTRACT FROM AUTHOR]

The Salt-Overly-Sensitive (SOS) signaling module, comprising the sodium-transport protein SOS1 and the regulatory proteins SOS2 and SOS3, is well known as the central salt excretion system, which helps protect plants against salt stress. Here we report that VPS23A, a component of the ESCRT (endosomal sorting complex required for transport), plays an essential role in the function of the SOS module in conferring plant salt tolerance. VPS23A enhances the interaction of SOS2 and SOS3. In the presence of salt stress, VPS23A positively regulates the redistribution of SOS2 to the plasma membrane, which then activates the antiporter activity of SOS1 to reduce Na+ accumulation in plant cells. Genetic evidence demonstrated that plant salt tolerance achieved by the overexpression of SOS2 and SOS3 dependeds on VPS23A. Taken together, our results revealed that VPS23A is a crucial regulator of the SOS module and affects the localization of SOS2 to the cell membrane. Moreover, the strong salt tolerance of Arabidopsis seedlings conferred by the engineered membrane-bound SOS2 revealed the significance of SOS2 sorting to the cell membrane in achieving its function, providing a potential strategy for crop salt tolerance engineering. This study reveals that the ESCRT-I component VPS23A confers salt tolerance by strengthening the SOS module. Under salt stress, VPS23A recruits SOS2 to the membrane and enhances the affinity between SOS2 and SOS3 to enhance SOS1 activity and thus regulate Na+/K+ homeostasis in plants. Interesingly, this study shows that an engineered membrane-bound SOS2 can greatly enhanceplant salt tolerance, providing a potential strategy for crop salt tolerance engineering. [ABSTRACT FROM AUTHOR]

The ubiquitin-proteasome system (UPS) is an important post-translational regulatory mechanism that controls many cellular functions in eukaryotes. Here, we show that stable expression of P3 protein encoded by Rice grassy stunt virus (RGSV), a negative-strand RNA virus in the Bunyavirales , causes developmental abnormities similar to the disease symptoms caused by RGSV, such as dwarfing and excess tillering, in transgenic rice plants. We found that both transgenic expression of P3 and RGSV infection induce ubiquitination and UPS-dependent degradation of rice NUCLEAR RNA POLYMERASE D1a (OsNRPD1a), one of two orthologs of the largest subunit of plant-specific RNA polymerase IV (Pol IV), which is required for RNA-directed DNA methylation (RdDM). Furthermore, we identified a P3-inducible U-box type E3 ubiquitin ligase, designated as P3-inducible protein 1 (P3IP1), which interacts with OsNRPD1a and mediates its ubiquitination and UPS-dependent degradation in vitro and in vivo. Notably, both knockdown of OsNRPD1 and overexpression of P3IP1 in rice plants induced developmental phenotypes similar to RGSV disease symptomss. Taken together, our findings reveal a novel virulence mechanism whereby plant pathogens target host RNA Pol IV for UPS-dependent degradation to induce disease symptoms. Our study also identified an E3 ubiquitin ligase, which targets the RdDM compotent NRPD1 for UPS-mediated degradation in rice. The ubiquitin-proteasome system (UPS) regulates many cellular functions in eukaryotic cells. This study reveals that a Bunyavirus-encoded virulence protein, P3, promotes the UPS-mediated degradation of an RdDM component, OsNRPD1, via a U-box type E3 ubiquitin ligase P3IP1, leading to disease symptom development in rice. [ABSTRACT FROM AUTHOR]

Bird predation during seed maturation causes great loss to agricultural production. In this study, through GWAS analysis of a large-scale sorghum germplasm diversity panel, we identified that Tannin1 , which encodes a WD40 protein functioning in the WD40/MYB/bHLH complex, controls bird feeding behavior in sorghum. Metabolic profiling analysis showed that a group of sorghum accessions preferred by birds contain mutated tan1-a / b alleles and accumulate significantly lower levels of anthocyanins and condensed tannin compounds. In contrast, a variety of aromatic and fatty acid-derived volatiles accumulate at significantly higher levels in these bird-preference accessions. We subsequently conducted both sparrow feeding and sparrow volatile attractant assays, which confirmed, respectively, the antifeedant and attractant functions of these differentially accumulated metabolites. In addition, the connection between the biosynthesis pathway of anthocyanin and proanthocyanidin and the pathway of fatty acid–derived volatile biosynthesis was demonstrated by discovering that Tannin1 complex modulates fatty acid biosynthesis by regulating the expression of SbGL2 in sorghum, thus affecting the accumulation of fatty acid-derived volatiles. Taken together, our study identified Tannin1 as the gene underlying the major locus controlling bird feeding behavior in sorghum, illustrating an example of the identification of an ecologically impactful molecular mechanism from field observation and providing significant insights into the chemistry of bird–plant ecological interactions. This study identified that Tannin1 , which encodes a WD40 protein functioning in the WD40/MYB/bHLH complex, control bird feeding behavior in sorghum. Tannin1 was found to differentially modulate the biosynthesis of anthocyanins and proanthocyanidins as well as the accumulation of fatty acid-derived volatiles, providing significant insights into the chemistry of bird–plant ecological interactions. [ABSTRACT FROM AUTHOR]

Summary Programmed cell death (PCD) and immunity in plants are tightly controlled to promote antimicrobial defense while preventing autoimmunity. However, the mechanisms contributing to this immune homeostasis are poorly understood. Here, we isolated a rice mutant ebr1 ( enhanced blight and blast resistance 1 ) that shows enhanced broad-spectrum bacterial and fungal disease resistance, but displays spontaneous PCD, autoimmunity, and stunted growth. EBR1 encodes an E3 ubiquitin ligase that interacts with OsBAG4, which belongs to the BAG (Bcl-2-associated athanogene) family that functions in cell death, growth arrest, and immune responses in mammals. EBR1 directly targets OsBAG4 for ubiquitination-mediated degradation. Elevated levels of OsBAG4 in rice are necessary and sufficient to trigger PCD and enhanced disease resistance to pathogenic infection, most likely by activating pathogen-associated molecular patterns-triggered immunity (PTI). Together, our study suggests that an E3-BAG module orchestrates innate immune homeostasis and coordinates the trade-off between defense and growth in plants. [ABSTRACT FROM AUTHOR]

Recent discovery of PYR/PYL/RCAR-type abscisic acid (ABA) receptors has become one of most significant advances in plant science in the past decade. In mammals, endosomal sorting acts as an important pathway to downregulate different types of receptors, but its role in plant hormone signaling is poorly understood. Here, we report that an ubiquitin E2-like protein, VPS23A, which is a key component of ESCRT-I, negatively regulates ABA signaling. VPS23A has epistatic relationship with PYR / PYL / RCAR -type ABA receptors and disruption of VPS23A enhanced the activity of key kinase OST1 in the ABA signaling pathway under ABA treatment. Moreover, VPS23A interacts with PYR1/PYLs and K63-linked diubiquitin, and PYL4 possesses K63-linked ubiquitinated modification in vivo . Further analysis revealed that VPS23A affects the subcellular localization of PYR1 and the stability of PYL4. Taken together, our results suggest that VPS23A affects PYR1/PYL4 via vacuole-mediated degradation, providing an advanced understanding of both the turnover of ABA receptors and ESCRTs in plant hormone signaling. [ABSTRACT FROM AUTHOR]

The βC1 protein encoded by the Tomato yellow leaf curl China virus -associated betasatellite functions as a pathogenicity determinant. To better understand the molecular basis whereby βC1 functions in pathogenicity, a yeast two-hybrid screen of a tobacco cDNA library was carried out using βC1 as the bait. The screen revealed that βC1 interacts with a tobacco RING-finger protein designated NtRFP1, which was further confirmed by the bimolecular fluorescence complementation and co-immunoprecipitation assays in Nicotiana benthamiana cells. Expression of NtRFP1 was induced by βC1, and in vitro ubiquitination assays showed that NtRFP1 is a functional E3 ubiquitin ligase that mediates βC1 ubiquitination. In addition, βC1 was shown to be ubiquitinated in vivo and degraded by the plant 26S proteasome. After viral infection, plants overexpressing NtRFP1 developed attenuated symptoms, whereas plants with silenced expression of NtRFP1 showed severe symptoms. Other lines of evidence showed that NtRFP1 attenuates βC1-induced symptoms through promoting its degradation by the 26S proteasome. Taken together, our results suggest that tobacco RING E3 ligase NtRFP1 attenuates disease symptoms by interacting with βC1 to mediate its ubiquitination and degradation via the ubiquitin/26S proteasome system. [ABSTRACT FROM AUTHOR]

Protein post-translational modification (PTM) by ubiquitination has been observed during many aspects of plant growth, development, and stress responses. The ubiquitin–proteasome system precisely regulates phytohormone signaling by affecting protein activity, localization, assembly, and interaction ability. Abscisic acid (ABA) is a major phytohormone, and plays important roles in plants under normal or stressed growth conditions. The ABA signaling pathway is composed of phosphatases, kinases, transcription factors, and membrane ion channels. It has been reported that multiple ABA signaling transducers are subjected to the regulations by ubiquitination. In particular, recent studies have identified different types of E3 ligases that mediate ubiquitination of ABA receptors in different cell compartments. This review focuses on modulation of these components by monoubiquitination or polyubiquitination that occurs in the plasma membrane, endomembranes, and from the cytosol to the nucleus; this implies the existence of retrograde and trafficking processes that are regulated by ubiquitination in ABA signaling. A number of single-unit E3 ligases, components of multi-subunit E3 ligases, E2s, and specific subunits of the 26S proteasome involved in ABA signal regulation are discussed. Dissecting the precise functions of ubiquitination in the ABA pathway may help us understand key factors in the signaling of other phytohormones regulated by ubiquitination and other types of PTMs. [ABSTRACT FROM AUTHOR]

Seed plants have evolved to maintain the dormancy of freshly matured seeds until the appropriate time for germination. Seed dormancy and germination are distinct physiological processes, and the transition from dormancy to germination is not only a critical developmental step in the life cycle of plants but is also important for agricultural production. These processes are precisely regulated by diverse endogenous hormones and environmental cues. Although ABA (abscisic acid) and GAs (gibberellins) are known to be the primary phytohormones that antagonistically regulate seed dormancy, recent findings demonstrate that another phytohormone, auxin, is also critical for inducing and maintaining seed dormancy, and therefore might act as a key protector of seed dormancy. In this review, we summarize our current understanding of the sophisticated molecular networks involving the critical roles of phytohormones in regulating seed dormancy and germination, in which AP2-domain-containing transcription factors play key roles. We also discuss the interactions (crosstalk) of diverse hormonal signals in seed dormancy and germination, focusing on the ABA/GA balance that constitutes the central node. [ABSTRACT FROM AUTHOR]

The article talks about editing high-efficiency genome in Arabidopsis, which uses YAO promoter-driven CRISPR/Cas9 system.

A letter to the editor is presented in response to the article about Abscisic acid (ABA) in Arabidopsis in the previous issue.

Summary Genetic drivers of cancer can be dysregulated through epigenetic modifications of DNA. Although the critical role of DNA 5-methylcytosine (5mC) in the regulation of transcription is recognized, the functions of other non-canonical DNA modifications remain obscure. Here, we report the identification of novel N 6 -methyladenine (N 6 -mA) DNA modifications in human tissues and implicate this epigenetic mark in human disease, specifically the highly malignant brain cancer glioblastoma. Glioblastoma markedly upregulated N 6 -mA levels, which co-localized with heterochromatic histone modifications, predominantly H3K9me3. N 6 -mA levels were dynamically regulated by the DNA demethylase ALKBH1, depletion of which led to transcriptional silencing of oncogenic pathways through decreasing chromatin accessibility. Targeting the N 6 -mA regulator ALKBH1 in patient-derived human glioblastoma models inhibited tumor cell proliferation and extended the survival of tumor-bearing mice, supporting this novel DNA modification as a potential therapeutic target for glioblastoma. Collectively, our results uncover a novel epigenetic node in cancer through the DNA modification N 6 -mA. Graphical Abstract Highlights • N 6 -methyladenine DNA modification is markedly upregulated in glioblastoma • N 6 -mA co-localizes with H3K9me3-marked heterochromatin domains • The DNA demethylase ALKBH1 dynamically controls N 6 -mA levels • Targeting N 6 -mA regulation kills glioblastoma stem cells N 6 -methyladenine DNA modifications are enriched in human glioblastoma, and targeting regulators of this modification can inhibit cancer growth by altering heterochromatin landscapes and downregulating oncogenic programs. [ABSTRACT FROM AUTHOR]

Microglial reactivity to injury and disease is emerging as a heterogeneous, dynamic, and crucial determinant in neurological disorders. However, the plasticity and fate of disease-associated microglia (DAM) remain largely unknown. We established a lineage tracing system, leveraging the expression dynamics of secreted phosphoprotein 1（ Spp1 ） to label and track DAM-like microglia during brain injury and recovery. Fate mapping of Spp1 + microglia during stroke in juvenile mice revealed an irreversible state of DAM-like microglia that were ultimately eliminated from the injured brain. By contrast, DAM-like microglia in the neonatal stroke models exhibited high plasticity, regaining a homeostatic signature and integrating into the microglial network after recovery. Furthermore, neonatal injury had a lasting impact on microglia, rendering them intrinsically sensitized to subsequent immune challenges. Therefore, our findings highlight the plasticity and innate immune memory of neonatal microglia, shedding light on the fate of DAM-like microglia in various neuropathological conditions. [Display omitted] • Spp1 + microglia exhibit context- and age-dependent heterogeneity in neuropathologies • Fate mapping of Spp1 + microglia reveals irreversible removal of DAM in juvenile stroke • Neonatal DAM exhibits remarkable plasticity and regain homeostasis as stroke resolves • Neonatal DAM retains immune memory and increased sensitivity to future immune insults The fate of disease-associated microglia (DAM) in neuropathologies remains elusive. Lan et al. generated an Spp1 fate-mapping model to track DAM-like microglia and find that the plasticity of DAM is age dependent. Juvenile stroke leads to the elimination of DAM, whereas neonatal DAM exhibits high plasticity and reversibility after injury, along with heightened sensitivity to subsequent immune challenges. [ABSTRACT FROM AUTHOR]

Growth factor receptors rank among the most important oncogenic pathways, but pharmacologic inhibitors often demonstrate limited benefit as monotherapy. Here, we show that epidermal growth factor receptor (EGFR) signaling repressed N6-methyladenosine (m6A) levels in glioblastoma stem cells (GSCs), whereas genetic or pharmacologic EGFR targeting elevated m6A levels. Activated EGFR induced non-receptor tyrosine kinase SRC to phosphorylate the m6A demethylase, AlkB homolog 5 (ALKBH5), thereby inhibiting chromosomal maintenance 1 (CRM1)-mediated nuclear export of ALKBH5 to permit sustained mRNA m6A demethylation in the nucleus. ALKBH5 critically regulated ferroptosis through m6A modulation and YTH N6-methyladenosine RNA binding protein (YTHDF2)-mediated decay of the glutamate-cysteine ligase modifier subunit (GCLM). Pharmacologic targeting of ALKBH5 augmented the anti-tumor efficacy of EGFR and GCLM inhibitors, supporting an EGFR-ALKBH5-GCLM oncogenic axis. Collectively, EGFR reprograms the epitranscriptomic landscape through nuclear retention of the ALKBH5 demethylase to protect against ferroptosis, offering therapeutic paradigms for the treatment of lethal cancers. [Display omitted] • EGFR downregulates m6A levels by promoting ALKBH5 nuclear localization • SRC phosphorylates ALKBH5, reducing CRM1-mediated ALKBH5 nuclear export • EGFR-ALKBH5 protects GCLM decay via m6A to repress ferroptosis • Pharmacologic ALKBH5 inhibitors augment efficacy of EGFR and GCLM inhibitors Although growth receptor pathways commonly activate similar pathways, Lv et al. show that EGF signaling represses m6A levels in contrast to induction by PDGF. EGFR blocks ALKBH5 nuclear export, increasing m6A eraser function and suppression of ferroptosis through glutathione production. ALKBH5 inhibitors enhance the anti-tumor efficacy of EGFR or glutathione inhibitors. [ABSTRACT FROM AUTHOR]

Summary: Seasonal changes in day length are perceived by plant photoreceptors and transmitted to the circadian clock to modulate developmental responses such as flowering time. Blue-light-sensing cryptochromes, the E3 ubiquitin-ligase COP1, and clock-associated proteins ELF3 and GI regulate this process, although the regulatory link between them is unclear. Here we present data showing that COP1 acts with ELF3 to mediate day length signaling from CRY2 to GI within the photoperiod flowering pathway. We found that COP1 and ELF3 interact in vivo and show that ELF3 allows COP1 to interact with GI in vivo, leading to GI degradation in planta. Accordingly, mutation of COP1 or ELF3 disturbs the pattern of GI cyclic accumulation. We propose a model in which ELF3 acts as a substrate adaptor, enabling COP1 to modulate light input signal to the circadian clock through targeted destabilization of GI. [Copyright &y& Elsevier]

Summary Plant pattern recognition receptors (PRRs) perceive microbial and endogenous molecular patterns to activate immune signaling. The cytoplasmic kinase BIK1 acts downstream of multiple PRRs as a rate-limiting component, whose phosphorylation and accumulation are central to immune signal propagation. Previous work identified the calcium-dependent protein kinase CPK28 and heterotrimeric G proteins as negative and positive regulators of BIK1 accumulation, respectively. However, mechanisms underlying this regulation remain unknown. Here we show that the plant U-box proteins PUB25 and PUB26 are homologous E3 ligases that mark BIK1 for degradation to negatively regulate immunity. We demonstrate that the heterotrimeric G proteins inhibit PUB25/26 activity to stabilize BIK1, whereas CPK28 specifically phosphorylates conserved residues in PUB25/26 to enhance their activity and promote BIK1 degradation. Interestingly, PUB25/26 specifically target non-activated BIK1, suggesting that activated BIK1 is maintained for immune signaling. Our findings reveal a multi-protein regulatory module that enables robust yet tightly regulated immune responses. [ABSTRACT FROM AUTHOR]

Despite extensive investigations in mammals and yeasts, the importance and specificity of COMPASS-like complex, which catalyzes histone 3 lysine 4 methylation (H3K4me), are not fully understood in plants. Here, we report that JMJ28, a Jumonji C domain-containing protein in Arabidopsis, recognizes specific DNA motifs through a plant-specific WRC domain and acts as an interacting factor to guide the chromatin targeting of ATX1/2-containing COMPASS-like complex. JMJ28 associates with COMPASS-like complex in vivo via direct interaction with RBL. The DNA-binding activity of JMJ28 is essential for both the targeting specificity of ATX1/2-COMPASS and the deposition of H3K4me at specific loci but exhibit functional redundancy with alternative COMPASS-like complexes at other loci. Finally, we demonstrate that JMJ28 is a negative regulator of plant immunity. In summary, our findings reveal a plant-specific recruitment mechanism of COMPASS-like complex. These findings help to gain deeper insights into the regulatory mechanism of COMPASS-like complex in plants., Competing Interests: Declaration of interests The authors declare that they have no conflict of interest., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Dysregulated growth factor receptor pathways, RNA modifications, and metabolism each promote tumor heterogeneity. Here, we demonstrate that platelet-derived growth factor (PDGF) signaling induces N 6 -methyladenosine (m 6 A) accumulation in glioblastoma (GBM) stem cells (GSCs) to regulate mitophagy. PDGF ligands stimulate early growth response 1 (EGR1) transcription to induce methyltransferase-like 3 (METTL3) to promote GSC proliferation and self-renewal. Targeting the PDGF-METTL3 axis inhibits mitophagy by regulating m 6 A modification of optineurin (OPTN). Forced OPTN expression phenocopies PDGF inhibition, and OPTN levels portend longer survival of GBM patients; these results suggest a tumor-suppressive role for OPTN. Pharmacologic targeting of METTL3 augments anti-tumor efficacy of PDGF receptor (PDGFR) and mitophagy inhibitors in vitro and in vivo. Collectively, we define PDGF signaling as an upstream regulator of oncogenic m 6 A regulation, driving tumor metabolism to promote cancer stem cell maintenance, highlighting PDGF-METTL3-OPTN signaling as a GBM therapeutic target., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Despite mounting evidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) engagement with immune cells, most express little, if any, of the canonical receptor of SARS-CoV-2, angiotensin-converting enzyme 2 (ACE2). Here, using a myeloid cell receptor-focused ectopic expression screen, we identified several C-type lectins (DC-SIGN, L-SIGN, LSECtin, ASGR1, and CLEC10A) and Tweety family member 2 (TTYH2) as glycan-dependent binding partners of the SARS-CoV-2 spike. Except for TTYH2, these molecules primarily interacted with spike via regions outside of the receptor-binding domain. Single-cell RNA sequencing analysis of pulmonary cells from individuals with coronavirus disease 2019 (COVID-19) indicated predominant expression of these molecules on myeloid cells. Although these receptors do not support active replication of SARS-CoV-2, their engagement with the virus induced robust proinflammatory responses in myeloid cells that correlated with COVID-19 severity. We also generated a bispecific anti-spike nanobody that not only blocked ACE2-mediated infection but also the myeloid receptor-mediated proinflammatory responses. Our findings suggest that SARS-CoV-2-myeloid receptor interactions promote immune hyperactivation, which represents potential targets for COVID-19 therapy., Competing Interests: Declaration of interests J.W., Q.L., J.L., B.H., J.D., and Y.L. are named inventors on a patent application that describes the anti-SARS-CoV-2 blocking nanobodies. J.W. is a consultant for Lilly Asia Ventures and is on the Scientific Advisory Board of Rootpath Genomics, which is not relevant to this work. M.S.D. is a consultant for Inbios, Vir Biotechnology, and NGM Biopharmaceuticals and is on the Scientific Advisory Board of Moderna and Immunome. The Diamond laboratory has received unrelated funding support in sponsored research agreements from Moderna, Vir Biotechnology, and Emergent BioSolutions., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Cancer stem cells (CSCs) proactively remodel their microenvironment to maintain a supportive niche. Viewed through the lens of an ecosystem, numerous tumor components have multi-directional interactions involving CSCs, supporting the complexity of tumors to maintain growth in a dynamic host. In this Perspective, we discuss how CSCs are active architects of their microenvironment and drive interactions with other tumor components, such as immune cells, cancer-associated fibroblasts and differentiated cells, blood vessels, and other extracellular cues to engineer a sustainable niche. We also highlight considerations for modeling this dynamic tumor ecology and discuss potential therapeutic strategies for targeting these multifaceted interactions., (Copyright © 2018 Elsevier Inc. All rights reserved.)

The plant hormones brassinosteroids (BRs) participate in light-mediated regulation of plant growth, although the underlying mechanisms are far from being fully understood. In addition, the function of the core transcription factor in the BR signaling pathway, BRI1-EMS-SUPPRESSOR 1 (BES1), largely depends on its phosphorylation status and its protein stability, but the regulation of BES1 is not well understood. Here, we report that SINA of Arabidopsis thaliana (SINATs) specifically interact with dephosphorylated BES1 and mediate its ubiquitination and degradation. Our genetic data demonstrated that SINATs inhibit BR signaling in a BES1-dependent manner. Interestingly, we found that the protein levels of SINATs were decreased in the dark and increased in the light, which changed BES1 protein levels accordingly. Thus, our study not only uncovered a new mechanism of BES1 degradation but also provides significant insights into how light conditionally regulates plant growth through controlling accumulation of different forms of BES1., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Messenger RNA (mRNA) modification provides an additional layer of gene regulation in cells. In this issue of Cancer Cell, Zhang et al. report that ALKBH5, a demethylase of the mRNA modification N 6 -methyladenosine, regulates proliferation and self-renewal of glioblastoma stem-like cells by modulating pre-mRNA stability and expression of the FOXM1 gene., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Cold stress is a major environmental factor that limits plant growth and development. The C-repeat-binding factor (CBF)-dependent cold signaling pathway is extensively studied in Arabidopsis; however, the specific protein kinases involved in this pathway remain elusive. Here we report that OST1 (open stomata 1), a well-known Ser/Thr protein kinase in ABA signaling, acts upstream of CBFs to positively regulate freezing tolerance. The ost1 mutants show freezing hypersensitivity, whereas transgenic plants overexpressing OST1 exhibit enhanced freezing tolerance. The OST1 kinase is activated by cold stress. Moreover, OST1 interacts with both the transcription factor ICE1 and the E3 ligase HOS1 in the CBF pathway. Cold-activated OST1 phosphorylates ICE1 and enhances its stability and transcriptional activity. Meanwhile, OST1 interferes with the interaction between HOS1 and ICE1, thus suppressing HOS1-mediated ICE1 degradation under cold stress. Our results thus uncover the unexpected roles of OST1 in modulating CBF-dependent cold signaling in Arabidopsis., (Copyright © 2015 Elsevier Inc. All rights reserved.)

In this issue of Cell Stem Cell, Zhu et al. (2014) demonstrate that a genetically engineered glioma model displays a functional cellular hierarchy defined by expression of the nuclear orphan receptor Tlx. Targeting cancer stem cells through genetic deletion of TLX promotes cancer stem cell death and differentiation and extends survival., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Ubiquitination is an important protein post-translational modification, which is involved in various cellular processes in higher plants, and U-box E3 ligases play important roles in diverse functions in eukaryotes. Here, we describe the functions of Arabidopsis thaliana PUB19 (AtPUB19), which we demonstrated in an in vitro assay to encode a U-box type E3 ubiquitin ligase. AtPUB19 was up-regulated by drought, salt, cold, and abscisic acid (ABA). Down-regulation of AtPUB19 led to hypersensitivity to ABA, enhanced ABA-induced stomatal closing, and enhanced drought tolerance, while AtPUB19 overexpression resulted in the reverse phenotypes. Molecular analysis showed that the expression levels of a number of ABA and stress marker genes were altered in both AtPUB19 overexpressing and atpub19-1 mutant plants. In summary, our data show that AtPUB19 negatively regulates ABA and drought responses in A. thaliana., (© The Author 2011. Published by the Molecular Plant Shanghai Editorial Office in association with Oxford University Press on behalf of CSPB and IPPE, SIBS, CAS.)

Light and brassinosteroid (BR) antagonistically regulate the developmental switch from etiolation in the dark to photomorphogenesis in the light in plants. Here, we identify GATA2 as a key transcriptional regulator that mediates the crosstalk between BR- and light-signaling pathways. Overexpression of GATA2 causes constitutive photomorphogenesis in the dark, whereas suppression of GATA2 reduces photomorphogenesis caused by light, BR deficiency, or the constitutive photomorphogenesis mutant cop1. Genome profiling and chromatin immunoprecipitation experiments show that GATA2 directly regulates genes that respond to both light and BR. BR represses GATA2 transcription through the BR-activated transcription factor BZR1, whereas light causes accumulation of GATA2 protein and feedback inhibition of GATA2 transcription. Dark-induced proteasomal degradation of GATA2 is dependent on the COP1 E3 ubiquitin ligase, and COP1 can ubiquitinate GATA2 in vitro. This study illustrates a molecular framework for antagonistic regulation of gene expression and seedling photomorphogenesis by BR and light., (Copyright © 2010 Elsevier Inc. All rights reserved.)