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Sumoylation controls CLOCK-BMAL1-mediated clock resetting via CBP recruitment in nuclear transcriptional foci
- Sumoylation controls CLOCK-BMAL1-mediated clock resetting via CBP recruitment in nuclear transcriptional foci
- Lee, Y[Lee, Yool]; Chun, SK[Chun, Sung Kook]; Kim, K[Kim, Kyungjin]
- DGIST Authors
- Chun, SK[Chun, Sung Kook]; Kim, K[Kim, Kyungjin]
- Issue Date
- Biochimica Et Biophysica Acta: Molecular Cell Research, 1853(10), 2697-2708
- Article Type
- Amino Acid Substitution; Animal; Animal Cell; Animals; ARNTL Protein, Human; ARNTL Transcription Factors; BiFC-Based FRET; BMAL1; Bone Sialoprotein (35-62), Human; CBP; Cell Nucleus; Cell Nucleus Inclusion Body; Cercopithecus Aethiops; Chlorocebus Aethiops; Circadian Clock; Circadian Clocks; Circadian Rhythm; Clock Protein, Human; Clock Proteins; Clock Resetting; Complex Formation; Controlled Study; COS 1 Cell Line; COS Cells; Cyclic AMP Responsive Element Binding Protein Binding Protein; Cysteine Endopeptidases; Cysteine Proteinase; Fluorescence Resonance Energy Transfer; Gene Expression; Genetics; Human; Humans; Mammalia; Metabolism; Molecular Dynamics; Mutation; Non-Human; Nuclear Body; Peptide Fragment; Peptide Fragments; PER1 Protein; Physiology; Priority Journal; Protein Protein Interaction; Protein SUSP1; Proteinase; SENP6 Protein, Human; Sialoglycoprotein; Sialoglycoproteins; SUMO3 Protein; SUMO3 Protein, Human; Sumoylation; SUSP1; Transcription Factor ARNTL; Transcription Factor Clock; Transcription Termination; Ubiquitin; Ubiquitins; Unclassified Drug
- CLOCK-BMAL1 is a key transcription factor complex of the molecular clock system that generates circadian gene expression and physiology in mammals. Here, we demonstrate that sumoylation of BMAL1 mediates the rapid activation of CLOCK-BMAL1 by CREB-binding protein (CBP) in nuclear foci and also the resetting of the circadian clock. Under physiological conditions, a bimolecular fluorescence complementation-based fluorescence resonance energy transfer (BiFC-FRET) assay revealed that CLOCK-BMAL1 rapidly dimerized and formed a ternary complex with CBP in discrete nuclear foci in response to serum stimuli. We found that the formation of this ternary complex requires sumoylation of BMAL1 by SUMO3. These processes were abolished by both the ectopic expression of the SUMP2/3-specific protease, SUSP1, and mutation of the major sumoylation site (Lys259) of BMAL1. Moreover, molecular inhibition of BMAL1 sumoylation abrogated acute Per1 transcription and severely dampened the circadian gene oscillation triggered by clock synchronization stimuli. Taken together, these findings suggest that sumoylation plays a critical role in the spatiotemporal co-activation of CLOCK-BMAL1 by CBP for immediate-early Per induction and the resetting of the circadian clock. © 2015.
- Elsevier B.V.
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- Department of Brain and Cognitive SciencesBrain and BioClock Laboratory1. Journal Articles
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