Phosphorylation and nuclear translocation of BMAL1 (ARNTL) and CLOCK

Stable Identifier
R-HSA-9931529
Type
Pathway
Species
Homo sapiens
ReviewStatus
5/5
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Phosphorylation and nuclear translocation of BMAL1 (ARNTL) and CLOCK
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Post-translational modifications of circadian clock proteins provide additional levels of tempo control and metabolic control, as well as mechanisms for terminating transcriptional activation and activating proteolysis (reviewed in Lee et al. 2001, Hirano et al 2016, Alessandro et al. 2019).
After BMAL1 (ARNTL) and CLOCK are synthesized in the cytosol, CDK5 phosphorylates CLOCK (inferred from mouse homologs in Kwak et al. 2013) and CSNK2A1 (CK2alpha) phosphorylates BMAL1 (inferred from mouse homologs in Tamaru et al. 2009, Tamaru et al. 2015). The phosphorylated BMAL1 and CLOCK proteins heterodimerize (inferred from mouse homologs in Kondratov et al. 2003, Tamaru et al 2015) and are translocated to the nucleoplasm (inferred from mouse homologs in Tamaru et al. 2003, Kondratov et al. 2006, Kwon et al. 2006). NPAS2 can also heterodimerize with BMAL1 (Reick et al. 2001) and is presumed to undergo similar phosphorylation, however, this has not been directly demonstrated.
Literature References
PubMed ID Title Journal Year
12897057 BMAL1-dependent circadian oscillation of nuclear CLOCK: posttranslational events induced by dimerization of transcriptional activators of the mammalian clock system

Kondratov, RV, Chernov, MV, Kondratova, AA, Gorbacheva, VY, Gudkov, AV, Antoch, MP

Genes Dev 2003
11441147 NPAS2: an analog of clock operative in the mammalian forebrain

Reick, M, Garcia, JA, Dudley, C, McKnight, SL

Science 2001
26562092 CRY Drives Cyclic CK2-Mediated BMAL1 Phosphorylation to Control the Mammalian Circadian Clock

Tamaru, T, Hattori, M, Honda, K, Nakahata, Y, Sassone-Corsi, P, van der Horst, GT, Ozawa, T, Takamatsu, K

PLoS Biol 2015
27922612 The intricate dance of post-translational modifications in the rhythm of life

Hirano, A, Fu, YH, Ptácek, LJ

Nat Struct Mol Biol 2016
19330005 CK2alpha phosphorylates BMAL1 to regulate the mammalian clock

Tamaru, T, Hirayama, J, Isojima, Y, Nagai, K, Norioka, S, Takamatsu, K, Sassone-Corsi, P

Nat Struct Mol Biol 2009
16980631 BMAL1 shuttling controls transactivation and degradation of the CLOCK/BMAL1 heterodimer

Kwon, I, Lee, J, Chang, SH, Jung, NC, Lee, BJ, Son, GH, Kim, K, Lee, KH

Mol Cell Biol 2006
14750952 Nucleocytoplasmic shuttling and phosphorylation of BMAL1 are regulated by circadian clock in cultured fibroblasts

Tamaru, T, Isojima, Y, van der Horst, GT, Takei, K, Nagai, K, Takamatsu, K

Genes Cells 2003
11779462 Posttranslational mechanisms regulate the mammalian circadian clock

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

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

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

Cell Cycle 2006
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
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Authored
May, B  (2024-12-09)
Reviewed
Sancar, A  (2025-02-14)
Albrecht, U  (2025-02-18)
Created
May, B  (2024-12-12)
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