JNK regulates the photic response of the mammalian circadian clock
JNK regulates the photic response of the mammalian circadian clock
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DOI：
10.1038/embor.2012.37
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发表时间：
2012-05
期刊：
影响因子：
7.7
通讯作者：
H. Yoshitane;S. Honma;Kiyomichi Imamura;H. Nakajima;Shin‐ya Nishide;Daisuke Ono;H. Kiyota;Naoya Shinozaki;Hirokazu Matsuki;Naoya Wada;H. Doi;T. Hamada;K. Honma;Y. Fukada
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文献类型：
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作者：
H. Yoshitane;S. Honma;Kiyomichi Imamura;H. Nakajima;Shin‐ya Nishide;Daisuke Ono;H. Kiyota;Naoya Shinozaki;Hirokazu Matsuki;Naoya Wada;H. Doi;T. Hamada;K. Honma;Y. Fukada
哺乳动物时钟蛋白的翻译后调节被赋予了计时功能，但似乎还有更重要的作用。在这里，我们展示了通过 BMAL1 Ser 520/Thr 527/Ser 592 磷酸化抑制剂筛选鉴定出的 c-Jun N 末端激酶 (JNK) 对时钟具有动态调节作用。 JNK1 和 JNK2 的敲低会消除 BMAL1 磷酸化并延长成纤维细胞的昼夜节律。缺乏神经元特异性亚型 JNK3 的小鼠行为节律发生了改变，自由奔跑时间更长，光相移也受到影响。运动节律对恒定光的强度变化不敏感，这偏离了阿绍夫规则。因此，JNK 通过控制响应光的振荡速度和相位来调节生物钟的核心特征。
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.