title: In vivo role of phosphorylation of cryptochrome 2 in the mouse circadian clock.
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.
authors.affiliation: Department of Biological Sciences, Graduate School of Science, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
authors.forename: Arisa
authors.initials: A
authors.lastname: Hirano
authors.affiliation: Department of Biological Sciences, Graduate School of Science, The University of Tokyo, Bunkyo-ku, Tokyo, Japan Molecular Genetics Research Laboratory, Graduate School of Science, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Kurabayashi
authors.affiliation: Department of Biological Sciences, Graduate School of Science, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
authors.forename: Tomoki
authors.initials: T
authors.lastname: Nakagawa
authors.affiliation: Laboratory for Animal Resources and Genetic Engineering, RIKEN, Center for Developmental Biology, Chuou-ku, Kobe, Japan.
authors.forename: Go
authors.initials: G
authors.lastname: Shioi
authors.affiliation: Department of Radiation Biology and Medical Genetics, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Todo
authors.affiliation: Department of Biological Sciences, Graduate School of Science, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Hirota
authors.affiliation: Department of Biological Sciences, Graduate School of Science, The University of Tokyo, Bunkyo-ku, Tokyo, Japan sfukada@mail.ecc.u-tokyo.ac.jp.
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Fukada
mesh_terms: D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D057906:Circadian Clocks; D002940:Circadian Rhythm; D056931:Cryptochromes / Q000235:genetics* / Q000378:metabolism*; D005786:Gene Expression Regulation; D055879:Gene Knock-In Techniques; D008099:Liver / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009154:Mutation; D056950:Period Circadian Proteins / Q000235:genetics* / Q000378:metabolism*; D010766:Phosphorylation; D012694:Serine / Q000378:metabolism*
chemical_list: C538967:Cry2 protein, mouse; D056931:Cryptochromes; C513312:Per2 protein, mouse; D056950:Period Circadian Proteins; D012694:Serine