RNA content in the nucleolus alters p53 acetylation via MYBBP1A
RNA content in the nucleolus alters p53 acetylation via MYBBP1A
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DOI：
10.1038/emboj.2011.23
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发表时间：
2011-03-16
期刊：
影响因子：
11.4
通讯作者：
Yanagisawa, Junn
中科院分区：
文献类型：
--
作者：
Kuroda, Takao;Murayama, Akiko;Yanagisawa, Junn
许多外部和内部损伤会破坏核仁结构，由此产生的核仁应力会稳定并激活 p53。我们在此表明，核仁破坏会诱导 p53 的乙酰化和积累，而无需磷酸化。我们鉴定了三种核仁蛋白：MYBBP1A、RPL5 和 RPL11，它们参与 p53 乙酰化和积累。 MYBBP1A 通过核仁 RNA 与核仁相连。当 rRNA 转录受到核仁应激抑制时，MYBBP1A 易位到核质并促进 p53-p300 相互作用，从而增强 p53 乙酰化。我们还发现 RPL5 和 RPL11 是核仁输出 rRNA 所必需的。 RPL5 或 RPL11 的缺失会阻止 rRNA 输出，并抵消 rRNA 转录抑制引起的核仁 RNA 水平降低。结果，RPL5 或 RPL11 耗竭抑制了 MYBBP1A 易位和 p53 激活。我们的观察表明，RNA 生成和输出之间的动态平衡调节核仁 RNA 含量。核仁应激对这种平衡的扰动改变了核仁 RNA 含量并调节了 p53 活性。 EMBO 杂志 (2011) 30, 1054-1066。 doi：10.1038/emboj.2011.23； 2011 年 2 月 4 日在线发布
A number of external and internal insults disrupt nucleolar structure, and the resulting nucleolar stress stabilizes and activates p53. We show here that nucleolar disruption induces acetylation and accumulation of p53 without phosphorylation. We identified three nucleolar proteins, MYBBP1A, RPL5, and RPL11, involved in p53 acetylation and accumulation. MYBBP1A was tethered to the nucleolus through nucleolar RNA. When rRNA transcription was suppressed by nucleolar stress, MYBBP1A translocated to the nucleoplasm and facilitated p53-p300 interaction to enhance p53 acetylation. We also found that RPL5 and RPL11 were required for rRNA export from the nucleolus. Depletion of RPL5 or RPL11 blocked rRNA export and counteracted reduction of nucleolar RNA levels caused by inhibition of rRNA transcription. As a result, RPL5 or RPL11 depletion inhibited MYBBP1A translocation and p53 activation. Our observations indicated that a dynamic equilibrium between RNA generation and export regulated nucleolar RNA content. Perturbation of this balance by nucleolar stress altered the nucleolar RNA content and modulated p53 activity. The EMBO Journal (2011) 30, 1054-1066. doi:10.1038/emboj.2011.23; Published online 4 February 2011