Negative control of circadian clock regulator E4BP4 by casein kinase Iepsilon-mediated phosphorylation.
Light-dependent transcriptional regulation of clock genes is a crucial step in the entrainment of the circadian clock. E4bp4 is a light-inducible gene in the chick pineal gland, and it encodes a bZIP protein that represses transcription of cPer2, a chick pineal clock gene. Here, we demonstrate that prolonged light period-dependent accumulation of E4BP4 protein is temporally coordinated with a delay of the rising phase of cPer2 in the morning. E4BP4 was phosphorylated progressively and then disappeared in parallel with induced cPer2 expression. Characterization of E4BP4 revealed Ser182, a phosphoacceptor site located at the amino-terminal border of the Ser/Thr cluster, which forms the phosphorylation motifs for casein kinase 1epsilon (CK1epsilon). CK1epsilon physically associated with E4BP4 and phosphorylated it. CK1epsilon-catalyzed phosphorylation of E4BP4 resulted in proteasomal proteolysis-dependent decrease of E4BP4 levels, while E4BP4 nuclear accumulation was attenuated by CK1epsilon in a kinase activity-independent manner. CK1epsilon-mediated posttranslational regulation was accompanied by reduction of the transcriptional repression executed by E4BP4. These results not only demonstrate a phosphorylation-dependent regulatory mechanism for E4BP4 function but also highlight the role of CK1epsilon as a negative regulator for E4BP4-mediated repression of cPer2.[1]References
- Negative control of circadian clock regulator E4BP4 by casein kinase Iepsilon-mediated phosphorylation. Doi, M., Okano, T., Yujnovsky, I., Sassone-Corsi, P., Fukada, Y. Curr. Biol. (2004) [Pubmed]
Annotations and hyperlinks in this abstract are from individual authors of WikiGenes or automatically generated by the WikiGenes Data Mining Engine. The abstract is from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.About WikiGenesOpen Access LicencePrivacy PolicyTerms of Useapsburg
