Cry:Per heterodimer binds Bmal1:Clock,Npas2 heterodimer

Stable Identifier
R-MMU-508741
Type
Reaction [binding]
Species
Mus musculus
Compartment
nucleoplasm
ReviewStatus
5/5
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Cry:Per heterodimer binds Bmal1:Clock,Npas2 heterodimer
Cry (Cry1 and Cry2) and Per (Per1, Per2) proteins form complex in the cytoplasm where they are phosphorylated by Csnk1d and Csnk1e kinases. Cry:Per complexes appear to form stable complexes with a kinase. Because of the nuclear localization signal of Per, the complexes are translocated to the nucleus where they bind Bmal11:Clock/Npas2 (Arntl:Clock/Npas2) heterodimers and inhibit the transactivation activity of Bmal1:Clock/Npas2.
Cry and Per proteins are themselves transcriptionally activated by Bmal1:Clock/Npas2 thus they participate in a negative loop inhibiting their own synthesis and the synthesis of other targets of Bmal1:Clock/Npas2.
Experiments with two-hybrid interaction and in vitro association show that Cry1, Cry2, and Per2 bind Bmal1 at two different sites on Bmal1. Per2 but not Cry1 or Cry2 binds Clock. Different combinations of Per and Cry proteins in Per:Cry complexes have different inhibitory activities.
Literature References
PubMed ID Title Journal Year
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Bordon, A, Albrecht, U, Langmesser, S, Rusconi, S, Tallone, T

BMC Mol Biol 2008
10428031 mCRY1 and mCRY2 are essential components of the negative limb of the circadian clock feedback loop

Kume, K, Zylka, MJ, Hastings, MH, Reppert, SM, Maywood, ES, Shearman, LP, Jin, X, Sriram, S, Weaver, DR

Cell 1999
16987893 Molecular components of the mammalian circadian clock

Ko, CH, Takahashi, JS

Hum Mol Genet 2006
16507766 Dual role of the CLOCK/BMAL1 circadian complex in transcriptional regulation

Antoch, MP, Kondratova, AA, Gorbacheva, VY, Shamanna, RK, Kondratov, RV

FASEB J 2006
10807566 Interacting molecular loops in the mammalian circadian clock

Kume, K, Chaves, I, Hastings, MH, Reppert, SM, Maywood, ES, Lee, CC, Shearman, LP, Sriram, S, Zheng, B, van der Horst, GT, Weaver, DR

Science 2000
16777965 The BMAL1 C terminus regulates the circadian transcription feedback loop

Yagita, K, Tagao, S, Ueda, HR, Morita, A, Yasuda, M, Tamanini, F, Yamanaka, I, Sugisawa, Y, Kiyohara, YB, Kondo, T, van der Horst, GT

Proc Natl Acad Sci U S A 2006
11779462 Posttranslational mechanisms regulate the mammalian circadian clock

Loudon, AS, Cagampang, FR, Reppert, SM, Lee, C, Etchegaray, JP

Cell 2001
16628007 Post-translational regulation of circadian transcriptional CLOCK(NPAS2)/BMAL1 complex by CRYPTOCHROMES

Antoch, MP, Kondratova, AA, Gorbacheva, VY, Lee, C, Kondratov, RV, Chernov, MV

Cell Cycle 2006
12782655 Loss of circadian rhythmicity in aging mPer1-/-mCry2-/- mutant mice

Albrecht, U, Oster, H, Baeriswyl, S, van der Horst, GT

Genes Dev 2003
17115977 Cryptochromes impair phosphorylation of transcriptional activators in the clock: a general mechanism for circadian repression

Fortier, EE, Cermakian, N, Martineau, V, Dardente, H

Biochem J 2007
12381662 Disruption of mCry2 restores circadian rhythmicity in mPer2 mutant mice

Albrecht, U, Yasui, A, Oster, H, van der Horst, GT

Genes Dev 2002
18786386 Cellular circadian pacemaking and the role of cytosolic rhythms

Hastings, MH, Maywood, ES, O'Neill, JS

Curr Biol 2008
Participants
Input
Output
Orthologous Events
CRY:PER heterodimer binds the BMAL1:CLOCK/NPAS2 heterodimer (Homo sapiens)
Authored
May, B  (2010-02-20)
Reviewed
Delaunay, F  (2010-06-23)
Kay, SA  (2010-06-23)
Hirota, T  (2010-06-23)
Albrecht, U  (2010-06-23)
Created
May, B  (2010-02-16)
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