Inhibition of nucleolar stress response by Sirt1: A potential mechanism of acetylation-independent regulation of p53 accumulation
Inhibition of nucleolar stress response by Sirt1: A potential mechanism of acetylation-independent regulation of p53 accumulation
复制标题
Sirt1 抑制核仁应激反应：p53 积累的乙酰化独立调节的潜在机制
DOI：
10.1111/acel.12900
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发表时间：
2019-04-01
期刊：
影响因子：
7.8
通讯作者：
Jiang, Fan
中科院分区：
文献类型：
--
作者：
Bi, Xiaolei;Ye, Qing;Jiang, Fan
哺乳动物Sirt 1脱乙酰酶通常被认为是一种核蛋白，但一些初步研究表明，Sirt 1也可能参与协调核仁功能。在这里，我们表明，核仁应激反应是一种普遍存在的细胞反应，可以诱导不同类型的压力条件下，和Sirt 1是核仁应激反应的内源性抑制因子。利用稳定同位素标记的氨基酸在细胞培养的方法，我们已经确定了Sirt 1和核仁蛋白nucleophosmin之间的物理相互作用，这种蛋白质-蛋白质相互作用似乎是必要的Sirt 1抑制核仁胁迫，而Sirt 1的脱乙酰酶活性不是严格要求。基于报道的核仁应激反应在应激诱导的p53蛋白积累中的先决作用，我们还提供了证据表明，Sirt 1介导的对核仁应激反应的抑制可能代表了一种新的机制，通过这种机制，Sirt 1可以独立于赖氨酸脱乙酰化来调节细胞内p53的积累。这一过程可能代表了Sirt 1调节p53通路功能的另一种机制。
The mammalian Sirt1 deacetylase is generally thought to be a nuclear protein, but some pilot studies have suggested that Sirt1 may also be involved in orchestrating nucleolar functions. Here, we show that nucleolar stress response is a ubiquitous cellular reaction that can be induced by different types of stress conditions, and Sirt1 is an endogenous suppressor of nucleolar stress response. Using stable isotope labeling by amino acids in cell culture approach, we have identified a physical interaction of between Sirt1 and the nucleolar protein nucleophosmin, and this protein-protein interaction appears to be necessary for Sirt1 inhibition on nucleolar stress, whereas the deacetylase activity of Sirt1 is not strictly required. Based on the reported prerequisite role of nucleolar stress response in stress-induced p53 protein accumulation, we have also provided evidence suggesting that Sirt1-mediated inhibition on nucleolar stress response may represent a novel mechanism by which Sirt1 can modulate intracellular p53 accumulation independent of lysine deacetylation. This process may represent an alternative mechanism by which Sirt1 regulates functions of the p53 pathway.