Csnk1e,Csnk1d phosphorylate Cry and Per proteins

Stable Identifier
R-MMU-9909394
Type
Reaction [transition]
Species
Mus musculus
Compartment
cytosol
ReviewStatus
5/5
General
SVG | 
PNG
Low
Medium
High
 | PPTX  | SBGN
Csnk1e,Csnk1d phosphorylate Cry and Per proteins
In the cytosol the kinases casein kinase I delta (Csnk1d) and casein kinase I epsilon (Csnk1e) phosphorylate Per1 (Vielhaber et al. 2000, Lee et al. 2001, Akashi et al. 2002), Per2 (Lee et al. 2001, Akashi et al. 2002, Eide et al. 2005, Isojima et al. 2009), Per3 (Akashi et al. 2002, Lee et al. 2004), Cry1 (Eide et al. 2002), and Cry2 (Eide et al. 2002, Qin et al. 2015) at multiple sites when the Cry, Per, and kinase proteins are in a complex together (reviewed in Virshup et al. 2007). Evidence indicates that Per:Cry complexes form a stable ternary complex with either Csnk1e or Csnk1d (Lee et al. 2001).
Per1 protein contains a nuclear localization sequence (Vielhaber et al. 2000) and Per proteins contain nuclear export sequences (Vielhaber et al. 2001) allowing their movement into and out of the nucleus. Phosphorylation is required for transit of Per:Cry:Kinase complexes into the nucleus and for interaction of Per proteins with the ubiquitin-mediated degradation process in the cytoplasm.
Mouse Per2 is phosphorylatable at 21 residues (Vanselow et al. 2006). Phosphorylation at serine-659 (serine-662 in human PER2, which is mutated in one form of familial advanced sleep phase syndrome, FASPS) causes nuclear retention and stabilization of Per2, however the particular kinase responsible for phosphorylating serine-659 is unknown (Vanselow et al. 2006).
The kinase CK2 interacts with Csnk1e and enhances Csnk1e-dependent degradation of Per2 (Tsuchiya et al. 2009). Inhibition of the protein phosphatase PP1 by calyculinA or RNA interference causes hyperphosphorylation and increased nuclear accumulation of Per1 and Per2, indicating that PP1 negatively regulates phosphorylation of Per1 and Per2 (Lee et al. 2011, Schmutz et al. 2011)
Literature References
PubMed ID Title Journal Year
11865049 Control of intracellular dynamics of mammalian period proteins by casein kinase I epsilon (CKIepsilon) and CKIdelta in cultured cells

Akashi, M, Tsuchiya, Y, Yoshino, T, Nishida, E

Mol Cell Biol 2002
25994100 PER2 Differentially Regulates Clock Phosphorylation versus Transcription by Reciprocal Switching of CK1ε Activity

Qin, X, Mori, T, Zhang, Y, Johnson, CH

J Biol Rhythms 2015
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
15767683 Control of mammalian circadian rhythm by CKIepsilon-regulated proteasome-mediated PER2 degradation

Eide, EJ, Woolf, MF, Kang, H, Woolf, P, Hurst, W, Camacho, F, Vielhaber, EL, Giovanni, A, Virshup, DM

Mol Cell Biol 2005
11779462 Posttranslational mechanisms regulate the mammalian circadian clock

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

Cell 2001
19805222 CKIepsilon/delta-dependent phosphorylation is a temperature-insensitive, period-determining process in the mammalian circadian clock

Isojima, Y, Nakajima, M, Ukai, H, Fujishima, H, Yamada, RG, Masumoto, KH, Kiuchi, R, Ishida, M, Ukai-Tadenuma, M, Minami, Y, Kito, R, Nakao, K, Kishimoto, W, Yoo, SH, Shimomura, K, Takao, T, Takano, A, Kojima, T, Nagai, K, Sakaki, Y, Takahashi, JS, Ueda, HR

Proc Natl Acad Sci U S A 2009
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
Catalyst Activity

protein serine/threonine kinase activity of Cry1:Cry2:Per1:Per2:Per3:Csnk1e,Csnk1d [cytosol]

Physical Entity
Cry1:Cry2:Per1:Per2:Per3:Csnk1e,Csnk1d [cytosol] (Mus musculus)
Activity
protein serine/threonine kinase activity (GO:0004674)
This event is regulated
Negatively by
Regulator
PP1 catalytic subunit [cytosol] (Mus musculus)
Positively by
Regulator
CK2 [cytosol] (Mus musculus)
Orthologous Events
CSNK1E,CSNK1D phosphorylate CRY and PER proteins (Homo sapiens)
Authored
May, B  (2024-05-11)
Reviewed
Sancar, A  (2025-02-14)
Albrecht, U  (2025-02-18)
Created
May, B  (2024-05-13)
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