The CRY:PER:kinase complex represses transactivation by the BMAL:CLOCK (ARNTL:CLOCK) complex

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R-HSA-9931521
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Pathway
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Homo sapiens
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5/5
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The CRY:PER:kinase complex represses transactivation by the BMAL:CLOCK (ARNTL:CLOCK) complex
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A complex containing Cryptochrome proteins CRY1, CRY2, Period proteins PER1, PER2, PER3, and kinases CSNK1D and/or CSNK1E binds a heterodimer containing phosphorylated CLOCK and phosphorylated, acetylated BMAL1 bound to E-boxes in the promoters of target genes (inferred from mouse homologs in Griffin et al. 1999, Langmesser et al. 2008, Ye et al. 2011, Ye et al. 2014, Aryal et al. 2017, Cao et al. 2021). This effectively delivers the kinases CSNK1D and/or CSNK1E to the proximity of CLOCK, resulting in further phosphorylation of CLOCK (inferred from mouse homologs in Cao et al. 2021). NPAS2, which acts redundantly with CLOCK, may be similarly phosphorylated. The phosphorylation of CLOCK causes the dissociation of the BMAL1:CLOCK heterodimer from DNA (inferred from mouse homologs in Ye et al. 2014, Chiou et al. 2016, Cao et al. 2021), terminating the diurnal activation of gene expression by BMAL1:CLOCK.
Literature References
PubMed ID Title Journal Year
18430226 Interaction of circadian clock proteins PER2 and CRY with BMAL1 and CLOCK

Langmesser, S, Tallone, T, Bordon, A, Rusconi, S, Albrecht, U

BMC Mol Biol 2008
33443219 Molecular mechanism of the repressive phase of the mammalian circadian clock

Cao, X, Yang, Y, Selby, CP, Liu, Z, Sancar, A

Proc Natl Acad Sci U S A 2021
21613214 Biochemical analysis of the canonical model for the mammalian circadian clock

Ye, R, Selby, CP, Ozturk, N, Annayev, Y, Sancar, A

J Biol Chem 2011
27688755 Mammalian Period represses and de-represses transcription by displacing CLOCK-BMAL1 from promoters in a Cryptochrome-dependent manner

Chiou, YY, Yang, Y, Rashid, N, Ye, R, Selby, CP, Sancar, A

Proc. Natl. Acad. Sci. U.S.A. 2016
10531061 Light-independent role of CRY1 and CRY2 in the mammalian circadian clock

Griffin EA, Jr, Staknis, D, Weitz, CJ

Science 1999
28886335 Macromolecular Assemblies of the Mammalian Circadian Clock

Aryal, RP, Kwak, PB, Tamayo, AG, Gebert, M, Chiu, PL, Walz, T, Weitz, CJ

Mol Cell 2017
32304699 Molecular Links between the Circadian Clock and the Cell Cycle

Farshadi, E, van der Horst, GTJ, Chaves, I

J Mol Biol 2020
25228643 Dual modes of CLOCK:BMAL1 inhibition mediated by Cryptochrome and Period proteins in the mammalian circadian clock

Ye, R, Selby, CP, Chiou, YY, Ozkan-Dagliyan, I, Gaddameedhi, S, Sancar, A

Genes Dev 2014
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Authored
May, B  (2024-12-09)
Reviewed
Sancar, A  (2025-03-04)
Albrecht, U  (2025-03-04)
Created
May, B  (2024-12-12)
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