RRC ID 72572
Author Hirano A, Kurabayashi N, Nakagawa T, Shioi G, Todo T, Hirota T, Fukada Y.
Title In vivo role of phosphorylation of cryptochrome 2 in the mouse circadian clock.
Journal 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.
Volume 34(24)
Pages 4464-73
Published 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
Human and Animal Cells NIH3T3-3-4(RCB1862)