期刊
MOLECULAR AND CELLULAR BIOLOGY
卷 34, 期 24, 页码 4464-4473出版社
AMER SOC MICROBIOLOGY
DOI: 10.1128/MCB.00711-14
关键词
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资金
- Global COE program (Integrative Life Science Based on the Study of Biosignaling Mechanisms) from MEXT, Japan
- MEXT, Japan
- JSPS research fellowships for young scientists
The circadian clock is finely regulated by posttranslational modifications of clock components. Mouse CRY2, a critical player in the mammalian clock, is phosphorylated at Ser557 for proteasome-mediated degradation, but its in vivo role in circadian organization was not revealed. Here, we generated CRY2(S557A) mutant mice, in which Ser557 phosphorylation is specifically abolished. The mutation lengthened free-running periods of the behavioral rhythms and PER2:: LUC bioluminescence rhythms of cultured liver. In livers from mutant mice, the nuclear CRY2 level was elevated, with enhanced PER2 nuclear occupancy and suppression of E-box-regulated genes. Thus, Ser557 phosphorylation-dependent regulation of CRY2 is essential for proper clock oscillation in vivo.
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