JNK regulates the photic response of the mammalian circadian clock

EMBO Rep. 2012 May 1;13(5):455-61. doi: 10.1038/embor.2012.37.

Hikari Yoshitane ¹, Sato Honma, Kiyomichi Imamura, Hiroto Nakajima, Shin-ya Nishide, Daisuke Ono, Hiroshi Kiyota, Naoya Shinozaki, Hirokazu Matsuki, Naoya Wada, Hirofumi Doi, Toshiyuki Hamada, Ken-ichi Honma, Yoshitaka Fukada

Affiliations

Affiliation

1 Department of Biophysics and Biochemistry, Graduate School of Science, The University of Tokyo, Tokyo 113-0033, Japan.

PMID: 22441692 DOI: 10.1038/embor.2012.37

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.

Name
Email *

	Sorry, but the email address you supplied was invalid.