title: JNK regulates the photic response of the mammalian circadian clock.
abstract: The posttranslational regulation of mammalian clock proteins has been assigned a time-keeping function, but seems to have more essential roles. Here we show that c-Jun N-terminal kinase (JNK), identified by inhibitor screening of BMAL1 phosphorylation at Ser 520/Thr 527/Ser 592, confers dynamic regulation on the clock. Knockdown of JNK1 and JNK2 abrogates BMAL1 phosphorylation and lengthens circadian period in fibroblasts. Mice deficient for neuron-specific isoform JNK3 have altered behavioural rhythms, with longer free-running period and compromised phase shifts to light. The locomotor rhythms are insensitive to intensity variance of constant light, deviating from Aschoff's rule. Thus, JNK regulates a core characteristic of the circadian clock by controlling the oscillation speed and the phase in response to light.
authors.affiliation: Department of Biophysics and Biochemistry, Graduate School of Science, The University of Tokyo, Tokyo 113-0033, Japan.
authors.forename: Hikari
authors.initials: H
authors.lastname: Yoshitane
authors.forename: Sato
authors.initials: S
authors.lastname: Honma
authors.forename: Kiyomichi
authors.initials: K
authors.lastname: Imamura
authors.forename: Hiroto
authors.initials: H
authors.lastname: Nakajima
authors.forename: Shin-ya
authors.initials: SY
authors.lastname: Nishide
authors.forename: Daisuke
authors.initials: D
authors.lastname: Ono
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kiyota
authors.forename: Naoya
authors.initials: N
authors.lastname: Shinozaki
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Matsuki
authors.forename: Naoya
authors.initials: N
authors.lastname: Wada
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Doi
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Hamada
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Honma
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Fukada
mesh_terms: D056930:ARNTL Transcription Factors / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D057906:Circadian Clocks / Q000502:physiology; D006801:Humans; D015151:Immunoblotting; D047468:Immunoprecipitation; D048031:JNK Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D008322:Mammals / Q000378:metabolism / Q000502:physiology; D051379:Mice; D048057:Mitogen-Activated Protein Kinase 10 / Q000235:genetics / Q000378:metabolism; D048055:Mitogen-Activated Protein Kinase 8 / Q000235:genetics / Q000378:metabolism; D048056:Mitogen-Activated Protein Kinase 9 / Q000235:genetics / Q000378:metabolism; D009043:Motor Activity / Q000502:physiology; D041681:NIH 3T3 Cells; D010766:Phosphorylation / Q000235:genetics / Q000502:physiology; D013493:Suprachiasmatic Nucleus / Q000378:metabolism
chemical_list: D056930:ARNTL Transcription Factors; D048057:Mitogen-Activated Protein Kinase 10; D048056:Mitogen-Activated Protein Kinase 9; D048031:JNK Mitogen-Activated Protein Kinases; D048055:Mitogen-Activated Protein Kinase 8