Abstract
Clock proteins govern circadian physiology and their function is regulated by various mechanisms. Here we demonstrate that Casein kinase (CK)-2α phosphorylates the core circadian regulator BMAL1. Gene silencing of CK2α or mutation of the highly conserved CK2-phosphorylation site in BMAL1, Ser90, result in impaired nuclear BMAL1 accumulation and disruption of clock function. Notably, phosphorylation at Ser90 follows a rhythmic pattern. These findings reveal that CK2 is an essential regulator of the mammalian circadian system.
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Acknowledgements
We thank M. Okada and T. Takao for MS analysis, and E.G. Krebs, L. Dongxia, J. S. Takahashi, C.A. Bradfield, S.M. Reppert, D.R. Weaver, M. Ikeda and C. Nishio for reagents, discussions and help. This work was supported by the Human Frontiers in Science Program Organization and the Japanese Ministry of Education, Culture, Sports, Science and Technology (MEXT; T.T. and K.T.) and by the Cancer Research Coordinating Committee of the University of California and from the US National Institutes of Health (P.S.-C.).
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Tamaru, T., Hirayama, J., Isojima, Y. et al. CK2α phosphorylates BMAL1 to regulate the mammalian clock. Nat Struct Mol Biol 16, 446–448 (2009). https://doi.org/10.1038/nsmb.1578
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DOI: https://doi.org/10.1038/nsmb.1578
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