論文 - 詳細
RRC ID | 72572 |
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著者 | Hirano A, Kurabayashi N, Nakagawa T, Shioi G, Todo T, Hirota T, Fukada Y. |
タイトル | In vivo role of phosphorylation of cryptochrome 2 in the mouse circadian clock. |
ジャーナル | Mol Cell Biol |
Abstract |
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. |
巻・号 | 34(24) |
ページ | 4464-73 |
公開日 | 2014-12-1 |
DOI | 10.1128/MCB.00711-14 |
PII | MCB.00711-14 |
PMID | 25288642 |
PMC | PMC4248739 |
MeSH | Animals Cell Nucleus / metabolism Cells, Cultured Circadian Clocks Circadian Rhythm Cryptochromes / genetics* Cryptochromes / metabolism* Gene Expression Regulation Gene Knock-In Techniques Liver / metabolism Mice Mice, Inbred C57BL Mice, Transgenic Mutation Period Circadian Proteins / genetics* Period Circadian Proteins / metabolism* Phosphorylation Serine / metabolism* |
IF | 3.611 |
リソース情報 | |
ヒト・動物細胞 | NIH3T3-3-4(RCB1862) |