Circadian rhythms. Decoupling circadian clock protein turnover from circadian period determination.
Circadian rhythms. Decoupling circadian clock protein turnover from circadian period determination.
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DOI：
10.1126/science.1257277
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发表时间：
2015-01-30
期刊：
影响因子：
--
通讯作者：
Dunlap JC
中科院分区：
文献类型：
--
作者：
Larrondo LF;Olivares-Yañez C;Baker CL;Loros JJ;Dunlap JC
真核生物昼夜节律振荡器在不同的模型系统，如脉孢菌，果蝇，和哺乳动物细胞的机制基础被认为是一个转录和抑制为基础的负反馈回路，其中一个或多个负元件的渐进和控制磷酸化最终elaborates自己的蛋白酶体介导的降解，从而释放负反馈和确定昼夜节律周期的长度。粗糙脉孢菌昼夜节律负元件频率（FRQ）证实了这些蛋白质;它在100多个位点上逐渐磷酸化，并且具有异常磷酸化的frq等位基因的菌株显示FRQ的异常稳定性，这与改变的周期或明显的周期性密切相关。出乎意料的是，我们揭示了正常的昼夜节律振荡，反映了等位基因状态的FRQ，但坚持在没有典型的降解FRQ。这种明显的负性元素周转与昼夜节律周期长度决定的解偶联与共识的真核生物昼夜节律模型不一致。
The mechanistic basis of eukaryotic circadian oscillators in model systems as diverse as Neurospora, Drosophila, and mammalian cells is thought to be a transcription-and-translation–based negative feedback loop, wherein progressive and controlled phosphorylation of one or more negative elements ultimately elicits their own proteasome-mediated degradation, thereby releasing negative feedback and determining circadian period length. The Neurospora crassa circadian negative element FREQUENCY (FRQ) exemplifies such proteins; it is progressively phosphorylated at more than 100 sites, and strains bearing alleles of frq with anomalous phosphorylation display abnormal stability of FRQ that is well correlated with altered periods or apparent arrhythmicity. Unexpectedly, we unveiled normal circadian oscillations that reflect the allelic state of frq but that persist in the absence of typical degradation of FRQ. This manifest uncoupling of negative element turnover from circadian period length determination is not consistent with the consensus eukaryotic circadian model.
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