Ser392 phosphorylation modulated a switch between p53 and transcriptional condensates
Ser392 phosphorylation modulated a switch between p53 and transcriptional condensates
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Ser392 磷酸化调节 p53 和转录缩合物之间的转换
DOI：
10.1016/j.bbagrm.2022.194827
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发表时间：
2022-05-26
影响因子：
4.7
通讯作者：
Yang, Xiaorong
中科院分区：
文献类型：
--
作者：
Dai, Zhuojun;Li, Guoli;Yang, Xiaorong
人类P53是一种转录因子，调节多种靶基因的转录。在不同的应激条件下，其抑癌功能通过P53的磷酸化而被激活。在本研究中，我们发现野生型P53全长在体外和体内都能形成具有聚集趋势的相分离凝聚体。P53的LLP受多个功能结构域的调控。特异性DNA可促进P53凝聚体的形成。光漂白后的荧光恢复数据显示，Ser392的磷酸化增强了P53凝聚体的流动性。荧光分析表明，Ser392的磷酸化增加了参与转录启动的凝集物中的P53浓度，并增加了P53介导的转录凝集物的稳定性。细胞内实验表明，P53均匀分布在细胞核内，在紫外线诱导的DNA损伤下形成动态凝聚体，Ser392非磷酸化突变体S392AP53形成凝聚体，数量和大小明显减少。这些发现表明，P53的磷酸化改变了其LLP行为，并提示了一种磷酸化调节凝集物偏好的机制。
Human p53 is a transcription factor regulating the transcription of a variety of target genes. Under various stresses, its tumor suppressor function was activated by the phosphorylation of p53. In this study, we found that full-length wild-type p53 could form phase-separated condensates with the aggregation tendency in vitro and in vivo. The LLPS of p53 was regulated by multiple functional domains. Specific DNA could promote the formation of p53 condensates. Fluorescence recovery data after photobleaching revealed that the Ser392 phosphorylation enhanced the fluidity of p53 condensates. Fluorescence analysis suggested that Ser392 phosphorylation increased the p53 concentration in condensates involved in transcription initiation and the stability of p53-mediated transcriptional condensates. The experiments in cells showed that p53 was evenly dispersed in the nucleus, it formed the dynamic condensates under the UV radiation-induced DNA damage, and the Ser392 nonphosphorylatable mutant S392A p53 formed condensates with significantly reduced number and size. These findings revealed that p53 phosphorylation modified its LLPS behavior, and suggested a mechanism that phosphorylation regulated condensate preference.