Negative control of circadian clock regulator E4BP4 by casein kinase Iε-mediated phosphorylation

Masao Doi, Toshiyuki Okano, Irene Yujnovsky, Paolo Sassone-Corsi, Yoshitaka Fukada

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

Light-dependent transcriptional regulation of clock genes is a crucial step in the entrainment of the circadian clock [1]. E4bp4 is a light-inducible gene in the chick pineal gland [2], and it encodes a bZIP protein that represses transcription of cPer2, a chick pineal clock gene [2, 3]. 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 1ε (CK1ε). CK1ε physically associated with E4BP4 and phosphorylated it. CK1ε-catalyzed phosphorylation of E4BP4 resulted in proteasomal proteolysis-dependent decrease of E4BP4 levels, while E4BP4 nuclear accumulation was attenuated by CK1ε in a kinase activity-independent manner. CK1ε-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 CK1ε as a negative regulator for E4BP4-mediated repression of cPer2.

Original languageEnglish
Pages (from-to)975-980
Number of pages6
JournalCurrent Biology
Volume14
Issue number11
DOIs
Publication statusPublished - 2004 Jun 8
Externally publishedYes

Fingerprint

Casein Kinase I
Circadian Clocks
Phosphorylation
circadian rhythm
Clocks
phosphorylation
Genes
Light
chicks
Basic-Leucine Zipper Transcription Factors
Proteolysis
pineal body
Pineal Gland
genes
photophase
Transcription
proteolysis
non-specific serine/threonine protein kinase
phosphotransferases (kinases)
Phosphotransferases

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)

Cite this

Negative control of circadian clock regulator E4BP4 by casein kinase Iε-mediated phosphorylation. / Doi, Masao; Okano, Toshiyuki; Yujnovsky, Irene; Sassone-Corsi, Paolo; Fukada, Yoshitaka.

In: Current Biology, Vol. 14, No. 11, 08.06.2004, p. 975-980.

Research output: Contribution to journalArticle

Doi, Masao ; Okano, Toshiyuki ; Yujnovsky, Irene ; Sassone-Corsi, Paolo ; Fukada, Yoshitaka. / Negative control of circadian clock regulator E4BP4 by casein kinase Iε-mediated phosphorylation. In: Current Biology. 2004 ; Vol. 14, No. 11. pp. 975-980.
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