p53 regulates Period2 expression and the circadian clock.
p53 regulates Period2 expression and the circadian clock.
复制标题
DOI：
10.1038/ncomms3444
复制
发表时间：
2013
影响因子：
16.6
通讯作者：
Lee, Cheng Chi
中科院分区：
文献类型：
--
作者：
Miki, Takao;Matsumoto, Tomoko;Zhao, Zhaoyang;Lee, Cheng Chi
昼夜节律调节和遗传毒性应激反应之间的相互联系机制仍然知之甚少。在这里，我们表明周期2（Per2）（一种昼夜节律调节因子）的表达直接受p53与Per2启动子中的反应元件结合的调节。该p53反应元件在进化上是保守的，并且与BMAL1/CLOCK结合及其Per2表达的转录激活关键的E-Box元件重叠。我们的研究表明，p53阻断BMAL1/CLOCK与Per2启动子的结合，导致Per2表达的抑制。在视交叉上核（SCN）中，p53表达及其与Per2启动子的结合受昼夜节律控制。SCN中的Per2表达因p53缺陷或Nutlin-3对p53的稳定而改变。在行为上，p53 −/−小鼠具有较短的周期长度，缺乏稳定性，并且在自由运行状态下，它们表现出对光脉冲的光夹带受损。我们的研究表明，p53调节小鼠的昼夜行为。
The mechanistic interconnectivity between circadian regulation and the genotoxic stress response remains poorly understood. Here we show that the expression of Period 2 (Per2), a circadian regulator, is directly regulated by p53 binding to a response element in the Per2 promoter. This p53 response element is evolutionarily conserved and overlaps with the E-Box element critical for BMAL1/CLOCK binding and its transcriptional activation of Per2 expression. Our studies reveal that p53 blocks BMAL1/CLOCK binding to the Per2 promoter leading to repression of Per2 expression. In the suprachiasmatic nucleus (SCN), p53 expression and its binding to the Per2 promoter are under circadian control. Per2 expression in the SCN is altered by p53 deficiency or stabilization of p53 by Nutlin-3. Behaviorally, p53−/− mice have a shorter period length that lacks stability and they exhibit impaired photo-entrainment to a light pulse under a free-running state. Our studies demonstrate that p53 modulates mouse circadian behavior.
登录
查看更多内容
影响因子：
7
作者：
Bieda, M;Xu, XQ;Farnham, PJ
通讯作者：
Farnham, PJ
影响因子：
64.8
作者：
DONEHOWER, LA;HARVEY, M;BRADLEY, A
通讯作者：
BRADLEY, A
影响因子：
6
作者：
Bjarnason, GA;Jordan, RCK;Sothern, RB
通讯作者：
Sothern, RB
影响因子：
10.5
作者：
Maier, B;Gluba, W;Scrable, H
通讯作者：
Scrable, H
影响因子：
5.3
作者：
Eide, EJ;Woolf, MF;Virshup, DM
通讯作者：
Virshup, DM