cAMP-dependent signaling as a core component of the mammalian circadian pacemaker.

cAMP-dependent signaling as a core component of the mammalian circadian pacemaker.
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DOI:
10.1126/science.1152506
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发表时间:
2008-05-16
期刊:
Science (New York, N.Y.)
影响因子:
--
通讯作者:
Hastings MH
Hastings MH
中科院分区:
其他
文献类型:
--
作者:
O'Neill JS;Maywood ES;Chesham JE;Takahashi JS;Hastings MH

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哺乳动物的昼夜节律时钟被模拟为转录和翻译后反馈回路,由此昼夜节律基因被其蛋白质产物周期性地抑制。我们发现,腺苷3′5′单磷酸(cAMP)信号构成了一个额外的,真正的组成部分的振荡网络。cAMP信号传导是有节奏的,并维持视交叉上核的转录环,决定振幅、相位和周期的典型起搏器特性。这种作用是普遍的,在外周哺乳动物组织和细胞系中是明显的,从而揭示了一个意想不到的点,在哺乳动物中的昼夜节律调节与现有的转录反馈模型有质的不同。我们建议,每日激活cAMP信号,由转录振荡器驱动,反过来又维持转录节奏的进展。以这种方式,时钟输出构成后续周期的输入。
The mammalian circadian clockwork is modelled as transcriptional and post-translational feedback loops, whereby circadian genes are periodically suppressed by their protein products. We show that adenosine 3′5′ monophosphate (cAMP) signalling constitutes an additional, bona fide component of the oscillatory network. cAMP signalling is rhythmic and sustains the transcriptional loop of the suprachiasmatic nucleus, determining canonical pacemaker properties of amplitude, phase and period. This role is general, being evident in peripheral mammalian tissues and cell lines, thus revealing an unanticipated point of circadian regulation in mammals qualitatively different from the existing transcriptional feedback model. We propose that daily activation of cAMP signalling, driven by the transcriptional oscillator, in turn sustains progression of transcriptional rhythms. In this way, clock output constitutes an input to subsequent cycles.
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