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Sci. Signal., 2 June 2009
Vol. 2, Issue 73, p. ra26
[DOI: 10.1126/scisignal.2000305]

RESEARCH

Involvement of the Protein Kinase CK2 in the Regulation of Mammalian Circadian Rhythms

Yoshiki Tsuchiya1*{dagger}, Makoto Akashi2*, Mitsuhiro Matsuda1, Kyoko Goto1, Yoshihiko Miyata1, Koichi Node3, and Eisuke Nishida1{ddagger}

1 Department of Cell and Developmental Biology, Graduate School of Biostudies, Kyoto University, Sakyo-ku, Kyoto 606-8502, Japan.
2 Department of Vascular Failure Research, Faculty of Medicine, Saga University, 5-1-1 Nabeshima, Saga 849-8501, Japan.
3 Department of Cardiovascular and Renal Medicine, Faculty of Medicine, Saga University, 5-1-1 Nabeshima, Saga 849-8501, Japan.

* These authors contributed equally to this work.

{dagger} Present address: Department of Medical Life Systems, Faculty of Life and Medical Sciences, Doshisha University, 1-3 Tatara Miyakodani, Kyotanabe City, Kyoto 610-0394, Japan.

Abstract: Posttranslational modifications of clock proteins are crucial to generating proper circadian rhythms of the correct length and amplitude. Here, we show that the protein kinase CK2 (casein kinase 2) plays a role in regulating the mammalian circadian clock. We found that inhibiting CK2 activity resulted in a decrease in the amplitude and an increase in the period of oscillations in circadian gene expression. CK2 specifically bound and phosphorylated PERIOD2 (PER2) and collaborated with the protein kinase CKI{varepsilon} to promote PER2 degradation. We also identified a CK2 phosphorylation site (serine-53) in PER2, whose phosphorylation played a role in fine-tuning circadian rhythms and regulating PER2 stability but was dispensable for the cooperative effect of CK2 and CKI{varepsilon}. Thus, our study identifies CK2 as a regulatory element of mammalian circadian rhythms and uncovers a role for CK2 in PER2 degradation.

{ddagger} To whom correspondence should be addressed. E-mail: L50174{at}sakura.kudpc.kyoto-u.ac.jp

Citation: Y. Tsuchiya, M. Akashi, M. Matsuda, K. Goto, Y. Miyata, K. Node, E. Nishida, Involvement of the Protein Kinase CK2 in the Regulation of Mammalian Circadian Rhythms. Sci. Signal. 2, ra26 (2009).

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