The Role of β-TrCP1 and β-TrCP2 in Circadian Rhythm Generation by Mediating Degradation of Clock Protein PER2

• DOI: 10.1093/jb/mvn112
• Publication Date: 2008-09-10T00:14:37Z
• Authors: Kanae Ohsaki; Katsutaka Oishi; Yuko Kozono; Keiko Nakayama; Keiichi I. Nakayama; Norio Ishida
• Keywords: PER2; Protein Degradation

The mammalian circadian clock proteins undergo a daily cycle of accumulation followed by phosphorylation and degradation. mechanism which degradation has not been fully understood. Circadian protein PERIOD2 (PER2) is shown to be the potential target F-box beta-TrCP1, component ubiquitin E3 ligase. Here, we show that beta-TrCP2 as well beta-TrCP1 PER2 in vitro. We also identified beta-TrCP binding site (m2) being recognized both beta-TrCP2. Luciferase-PER2 fusion system revealed m2 was responsible for stability PER2. role rhythm generation analysed real-time reporter assay revealing siRNA-mediated suppressions and/or attenuate oscillations NIH3T3 cell. beta-TrCP1-deficient mice, however, showed normal period length, light-induced phase-shift response behaviour expression PER2, suggesting dispensable central suprachiasmatic nucleus. Our study indicates were involved cell autonomous culture cells, although nucleus remains elucidated.