Journal of Biochemistry Advance Access published online on September 8, 2008
Journal of Biochemistry, doi:10.1093/jb/mvn112
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
© 2008 The Japanese Biochemical Society
The role of beta-TrCP1 and beta-TrCP2 in circadian rhythm generation by mediating degradation of clock protein PER2
1Clock Cell Biology Research Group, Advanced Industrial Science and Technology, Ibaraki
2Department of Functional Genomics, Graduate School of Medicine & School of Medicine, Tohoku University, Sendai
3Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, Fukuoka
4Graduate School of Life and Environmental Sciences, University of Tsukuba, Ibaraki, Japan
*Correspond to N. ISHIDA in Clock Cell Biology Research Group, Advanced Industrial Science and Technology. Central6 1-1-1 Higashi, Tsukuba, 305-8566, Japan. E-mail: n.ishida{at}aist.go.jp, Telephone: +81-29-861-6053, Fax: +81-29-861-9499.
Received June 6, 2008; Accepted August 14, 2008
 |
Abstract |
|---|
The mammalian circadian clock proteins undergo a daily cycle of accumulation followed by phosphorylation and degradation. The mechanism by which clock proteins undergo degradation has not been fully understood. Circadian clock protein PERIOD2 (PER2) is shown to be the potential target of F-box protein ß-TrCP1, a component of ubiquitin E3 ligase. Here, we show that ß-TrCP2 as well as ß-TrCP1 target PER2 protein in vitro. We also identified ß-TrCP binding site (m2) of PER2 being recognized by both ß-TrCP1 and ß-TrCP2. Luciferase-PER2 fusion system revealed that m2 site was responsible for the stability of PER2. The role of ß-TrCP1 and ß-TrCP2 in circadian rhythm generation was analyzed by real-time reporter assay revealing that siRNA-mediated suppressions of ß-TrCP1 and/or ß-TrCP2 attenuate circadian oscillations in NIH3T3 cell. ß-TrCP1-deficient mice, however, showed normal period length, light-induced phase-shift response in behavior and normal expression of PER2, suggesting that ß-TrCP1 is dispensable for the central clock in the suprachiasmatic nucleus (SCN). Our study indicates ß-TrCP1 and ß-TrCP2 were involved in the cell autonomous circadian rhythm generation in culture cells, although the role of ß-TrCP2 in the central clock in the SCN remains to be elucidated.
Key Words: beta-TrCP, ubiquitin E3 ligase, F-box protein, knockout mouse, circadian rhythm
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  U. Schibler The 2008 Pittendrigh/Aschoff Lecture: Peripheral Phase Coordination in the Mammalian Circadian Timing System J Biol Rhythms, February 1, 2009; 24(1): 3 - 15. [Abstract] [PDF]
|
|