Cyclin-dependent kinase 5 (Cdk5) Regulates the Function of CLOCK protein by direct Phosphorylation
SCIE
SCOPUS
- Title
- Cyclin-dependent kinase 5 (Cdk5) Regulates the Function of CLOCK protein by direct Phosphorylation
- Authors
- Kwak, Y; Jeong, J; Lee, S; Park, YU; Lee, SA; Han, DH; Kim, JH; Ohshima, T; Mikoshiba, K; Suh, YH; Cho, S; Park, SK
- Date Issued
- 2013-12-27
- Publisher
- American Society of Biological Chemists
- Abstract
- Circadian rhythm is a biological rhythm governing physiology and behavior with a period of approximate to 24 h. At the molecular level, circadian output is controlled by a molecular clock composed of positive and negative feedback loops in transcriptional and post-translational processes. CLOCK is a transcription factor known as a central component of the molecular clock feedback loops generating circadian oscillation. Although CLOCK is known to undergo multiple post-translational modifications, the knowledge of their entities remains limited. Cyclin-dependent kinase 5 (Cdk5) is a proline-directed serine-threonine kinase that is involved in various neuronal processes. Here, we report that Cdk5 is a novel regulator of CLOCK protein. Cdk5 phosphorylates CLOCK at the Thr-451 and Thr-461 residues in association with transcriptional activation of CLOCK. The Cdk5-dependent regulation of CLOCK function is mediated by alterations of its stability and subcellular distribution. These results suggest that Cdk5 is a novel regulatory component of the core molecular clock machinery.
- URI
- https://oasis.postech.ac.kr/handle/2014.oak/14952
- DOI
- 10.1074/JBC.M113.494856
- ISSN
- 0021-9258
- Article Type
- Article
- Citation
- Journal of Biological Chemistry, vol. 288, no. 52, page. 36878 - 36889, 2013-12-27
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