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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.

SUBMITTER: Yoshitane H

PROVIDER: S-EPMC3343351 | biostudies-literature | 2012 May

REPOSITORIES: biostudies-literature

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JNK regulates the photic response of the mammalian circadian clock.

Yoshitane Hikari H Honma Sato S Imamura Kiyomichi K Nakajima Hiroto H Nishide Shin-ya SY Ono Daisuke D Kiyota Hiroshi H Shinozaki Naoya N Matsuki Hirokazu H Wada Naoya N Doi Hirofumi H Hamada Toshiyuki T Honma Ken-ichi K Fukada Yoshitaka Y

EMBO reports 20120501 5

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 ...[more]

PMID: 22441692

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