Formation of Cry:Per:Kinase complex

Stable Identifier
R-MMU-9909360
Type
Reaction [omitted]
Species
Mus musculus
Compartment
cytosol
ReviewStatus
5/5
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Formation of Cry:Per:Kinase complex
Cryptochrome (Cry1, Cry2) proteins, Period (Per1, Per2, Per3) proteins, and a kinase, Csnk1d or Csnk1e (CKIepsilon or CKIdelta), form a complex in the cytosol (Griffin et al. 1999, Kume et al. 1999, Field et al. 2000, Vielhaber et al. 2000, Eide et al. 2002, Lee et al. 2004, Lee et al. 2009, Nangle et al. 2014, Cao et al. 2023). Cry1, Cry2, Per1, Per2, Per3 and kinases assemble into a single large complex which enters the nucleus and binds Bmal1:Clock heterodimers (Aryal et al. 2017, Cao et al. 2023). The cytosolic complex is measured as 0.9-1.1 mDa (Aryal et al. 2017) and the nuclear complex is measured as 1.9 MDa (Aryal et al. 2017) or 707 kDa (Cao et al. 2023). Cry proteins contain nuclear localization signals, bind Per proteins (Kume et al. 1999, Nangle et al. 2014), and cause translocation of the complex into the nucleus (Kume et al. 1999). Phosphorylation of Per2 on serine-394 (serine-396 of the human homolog) by Cdk5 during the day increases the interaction between Per2 and Cry1 (Brenna et al. 2019). The association between Csnk1e and Per1 appears to mask a nuclear localization signal in Per1 and makes nuclear translocation of Per1 dependent on phosphorylation of Per1 (Vielhaber et al. 2000). Csnk1e binds and phosphorylates Per2 (Vielhaber et al. 2000). Per3 does not directly interact with Csnk1e (Lee et al. 2004). Csnk1e also phosphorylates Cry proteins and the phosphorylation is dependent on the interaction between Cry proteins and Per proteins, which may act as scaffolds (Eide et al. 2002).
Literature References
PubMed ID Title Journal Year
10428031 mCRY1 and mCRY2 are essential components of the negative limb of the circadian clock feedback loop

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

Cell 1999
10719897 Analysis of clock proteins in mouse SCN demonstrates phylogenetic divergence of the circadian clockwork and resetting mechanisms

Field, MD, Maywood, ES, O'Brien, JA, Weaver, DR, Reppert, SM, Hastings, MH

Neuron 2000
36682495 Analysis of mammalian circadian clock protein complexes over a circadian cycle

Cao, X, Wang, L, Selby, CP, Lindsey-Boltz, LA, Sancar, A

J Biol Chem 2023
11875063 The circadian regulatory proteins BMAL1 and cryptochromes are substrates of casein kinase Iepsilon

Eide, EJ, Vielhaber, EL, Hinz, WA, Virshup, DM

J Biol Chem 2002
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
25127877 Molecular assembly of the period-cryptochrome circadian transcriptional repressor complex

Nangle, SN, Rosensweig, C, Koike, N, Tei, H, Takahashi, JS, Green, CB, Zheng, N

Elife 2014
19948962 Essential roles of CKIdelta and CKIepsilon in the mammalian circadian clock

Lee, H, Chen, R, Lee, Y, Yoo, S, Lee, C

Proc Natl Acad Sci U S A 2009
31687929 Cyclin-dependent kinase 5 (CDK5) regulates the circadian clock

Brenna, A, Olejniczak, I, Chavan, R, Ripperger, JA, Langmesser, S, Cameroni, E, Hu, Z, De Virgilio, C, Dengjel, J, Albrecht, U

Elife 2019
14701732 Direct association between mouse PERIOD and CKIepsilon is critical for a functioning circadian clock

Lee, C, Weaver, DR, Reppert, SM

Mol Cell Biol 2004
10848614 Nuclear entry of the circadian regulator mPER1 is controlled by mammalian casein kinase I epsilon

Vielhaber, E, Eide, E, Rivers, A, Gao, ZH, Virshup, DM

Mol Cell Biol 2000
Participants
Input
Output
Orthologous Events
Formation of CRY:PER:Kinase complex (Homo sapiens)
Authored
May, B  (2024-05-13)
Reviewed
Sancar, A  (2025-02-14)
Albrecht, U  (2025-02-18)
Created
May, B  (2024-05-13)
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