O-GlcNAc Signaling Entrains the Circadian Clock by Inhibiting BMAL1/CLOCK Ubiquitination

Li, Min‐Dian; Ruan, Hai Bin; Hughes, Michael; Lee, Jeong Sang; Singh, Jay; Jones, Steven P.; Nitabach, Michael N.; Yang, Xiaoyong

doi:10.1016/j.cmet.2012.12.015

Cited by 176 publications

(161 citation statements)

References 33 publications

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“…In mammals, O-GlcNAc modification has been implicated in circadian clock function through regulating circadian clock genes, including PERIOD (49), BMAL1 (50), and CLOCK (51,52). Although these clock components are not conserved in plants, we found O-GlcNAc modification of proteins involved in plant circadian clock function, including TIME FOR COFFEE (TIC) (53).…”

Section: Potential Roles Of O-glcnacylation In the Circadian Clock Fmentioning

confidence: 75%

Proteomic analysis reveals O-GlcNAc modification on proteins with key regulatory functions in Arabidopsis

Chalkley

Maynard

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

113

161

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Genetic studies have shown essential functions of O-linked N-acetylglucosamine (O-GlcNAc) modification in plants. However, the proteins and sites subject to this posttranslational modification are largely unknown. Here, we report a large-scale proteomic identification of O-GlcNAc-modified proteins and sites in the model plant Arabidopsis thaliana. Using lectin weak affinity chromatography to enrich modified peptides, followed by mass spectrometry, we identified 971 O-GlcNAc-modified peptides belonging to 262 proteins. The modified proteins are involved in cellular regulatory processes, including transcription, translation, epigenetic gene regulation, and signal transduction. Many proteins have functions in developmental and physiological processes specific to plants, such as hormone responses and flower development. Mass spectrometric analysis of phosphopeptides from the same samples showed that a large number of peptides could be modified by either O-GlcNAcylation or phosphorylation, but cooccurrence of the two modifications in the same peptide molecule was rare. Our study generates a snapshot of the O-GlcNAc modification landscape in plants, indicating functions in many cellular regulation pathways and providing a powerful resource for further dissecting these functions at the molecular level.of proteins consisting of a single O-linked N-acetylglucosamine attached to serine and threonine residues. It has been extensively studied in animals, where it regulates a wide range of developmental and metabolic processes. O-GlcNAcylation is dynamically controlled by two enzymes: an O-GlcNAc transferase (OGT) and an O-GlcNAcase (OGA), which add and remove O-GlcNAc, respectively. O-GlcNAcylation occurs in the cytoplasm, nucleus, and mitochondria and has been implicated in cellular processes, including transcription, translation, signal transduction, nuclear pore function, epigenetic regulation and proteasomal degradation (1). Altered levels of protein O-GlcNAcylation in animals have been associated with neurodegeneration, diabetes, cardiovascular diseases, and cancer (2) whereas knock out of OGT is embryonically lethal (3).The model plant Arabidopsis has two putative OGTs: SPINDLY (SPY) and SECRET AGENT (SEC). The spy mutant was identified based on its phenotypes that mimic gibberellin-treated plants, with elongated stems (4). The spy plants also show defects in light and cytokinin responses, leaf morphology and phyllotaxy, root growth, meristem activity, and circadian rhythms (5). The sec mutant displays defects in flower development (6). Although OGT enzymatic activity has been demonstrated in SEC, similar activity in SPY has not been confirmed (7). However, the spy;sec double mutants show severe defects in the development of gametes and are embryonically lethal (7), similar to the OGT knockout mutant in animals. Thus, genetic evidence indicates that O-GlcNAc modification is as important in plants as in animals. But little is known about its specific functions because few O-GlcNAc-modified proteins have been identified...

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Section: Potential Roles Of O-glcnacylation In the Circadian Clock Fmentioning

confidence: 75%

Proteomic analysis reveals O-GlcNAc modification on proteins with key regulatory functions in Arabidopsis

Chalkley

Maynard

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

113

161

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“…Based on this data, we surmise that O-GlcNAcylation modulates the ubiquitination and subsequent degradation of the Nrf1a protein. Although the mechanism by which this occurs is not known currently, OGlcNAcylation exerting an effect on ubiquitination has also been reported for other proteins [62][63][64][65]. One possibility is that O-GlcNAc modified residues serves as docking sites for deubiquitinase enzymes that then removes ubiquitin from the protein.…”

Section: Discussionmentioning

confidence: 99%

Nuclear factor-erythroid-2 related transcription factor-1 (Nrf1) is regulated by O-GlcNAc transferase

Han

Valdez

et al. 2017

Free Radical Biology and Medicine

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A B S T R A C TThe Nrf1 (Nuclear factor E2-related factor 1) transcription factor performs a critical role in regulating cellular homeostasis. Using a proteomic approach, we identified Host Cell Factor-1 (HCF1), a co-regulator of transcription, and O-GlcNAc transferase (OGT), the enzyme that mediates protein O-GlcNAcylation, as cellular partners of Nrf1a, an isoform of Nrf1. Nrf1a directly interacts with HCF1 through the HCF1 binding motif (HBM), while interaction with OGT is mediated through HCF1. Overexpression of HCF1 and OGT leads to increased Nrf1a protein stability. Addition of O-GlcNAc decreases ubiquitination and degradation of Nrf1a. Transcriptional activation by Nrf1a is increased by OGT overexpression and treatment with PUGNAc. Together, these data suggest that OGT can act as a regulator of Nrf1a.

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“…Taken together, the studies by Ruan et al and Li et al define the OGT-HCF-1-BAP1 complex as a key modulator of ubiquitination, suggesting a novel mechanism by which OGlcNAcylation controls protein stability (13,46) (Fig. 1B).…”

Section: O-glcnacylation Stabilizes Proteins By Recruiting Deubiquitimentioning

confidence: 91%

“…Li et al further demonstrate that the OGT-BAP1 complex O-GlcNAcylates and deubiquitinates BMAL1 and CLOCK to control the amplitude of circadian oscillation in response to nutrient availability. Disruption of O-GlcNAc signaling in mouse liver perturbs the diurnal rhythm of glucose metabolism (46).…”

Section: O-glcnacylation Stabilizes Proteins By Recruiting Deubiquitimentioning

confidence: 99%

Regulation of Protein Degradation by O-GlcNAcylation: Crosstalk with Ubiquitination

Ruan

Nie

Yang

2013

Molecular & Cellular Proteomics

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154

119

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The post-translational modification of intracellular proteins by O-linked N-acetylglucosamine (O-GlcNAc) regulates essential cellular processes such as signal transduction, transcription, translation, and protein degradation. Misfolded, damaged, and unwanted proteins are tagged with a chain of ubiquitin moieties for degradation by the proteasome, which is critical for cellular homeostasis. In this review, we summarize the current knowledge of the interplay between O-GlcNAcylation and ubiquitination in the control of protein degradation. Understanding the mechanisms of action of O-GlcNAcylation in the ubiquitin-proteosome system shall facilitate the development of therapeutics for human diseases such as cancer, metabolic syndrome, and neurodegenerative diseases. Molecular & Cellular

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O-GlcNAc Signaling Entrains the Circadian Clock by Inhibiting BMAL1/CLOCK Ubiquitination

Cited by 176 publications

References 33 publications

Proteomic analysis reveals O-GlcNAc modification on proteins with key regulatory functions in Arabidopsis

Proteomic analysis reveals O-GlcNAc modification on proteins with key regulatory functions in Arabidopsis

Nuclear factor-erythroid-2 related transcription factor-1 (Nrf1) is regulated by O-GlcNAc transferase

Regulation of Protein Degradation by O-GlcNAcylation: Crosstalk with Ubiquitination

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