Novel Nucleolar Pathway Connecting Intracellular Energy Status with p53 Activation
Novel Nucleolar Pathway Connecting Intracellular Energy Status with p53 Activation
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DOI：
10.1074/jbc.m110.209916
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发表时间：
2011-06-10
影响因子：
4.8
通讯作者：
Yanagisawa, Junn
中科院分区：
文献类型：
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作者：
Kumazawa, Takuya;Nishimura, Kazuho;Yanagisawa, Junn
为了应对细胞内能量的短缺，哺乳动物细胞减少能量消耗并诱导细胞周期停滞，这两者都有助于细胞存活。在这里，我们报告了一种新的核仁途径，涉及能量依赖性核仁沉默复合物（eNoSC）和Myb结合蛋白1a（MYBBP1A）参与这些过程。也就是说，响应于葡萄糖饥饿，eNoSC抑制rRNA转录，这导致核仁RNA含量减少。因此，通过RNA锚定到核仁的MYBBP1A从核仁易位到核质。MYBBP1A通过增强p300和p53之间的相互作用，诱导p53的乙酰化和积累，最终导致细胞周期停滞（或凋亡）。总之，我们的研究结果表明，核仁作为一个传感器，将细胞内的能量状态转换到细胞周期机器。
In response to a shortage of intracellular energy, mammalian cells reduce energy consumption and induce cell cycle arrest, both of which contribute to cell survival. Here we report that a novel nucleolar pathway involving the energy-dependent nucleolar silencing complex (eNoSC) and Myb-binding protein 1a (MYBBP1A) is implicated in these processes. Namely, in response to glucose starvation, eNoSC suppresses rRNA transcription, which results in a reduction in nucleolar RNA content. As a consequence, MYBBP1A, which is anchored to the nucleolus via RNA, translocates from the nucleolus to the nucleoplasm. The translocated MYBBP1A induces acetylation and accumulation of p53 by enhancing the interaction between p300 and p53, which eventually leads to the cell cycle arrest (or apoptosis). Taken together, our results indicate that the nucleolus works as a sensor that transduces the intracellular energy status into the cell cycle machinery.