Acetylation of p62 regulates base excision repair through interaction with APE1
Acetylation of p62 regulates base excision repair through interaction with APE1
复制标题
p62 的乙酰化通过与 APE1 相互作用调节碱基切除修复
DOI：
10.1016/j.celrep.2022.111116
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发表时间：
2022
期刊：
影响因子：
8.8
通讯作者：
Haiying Wang
中科院分区：
文献类型：
--
作者：
Meiting Li;Jiannan Xiong;Liqian Yang;Jie Huang;Yu Zhang;Minghui Liu;Lina Wang;Jianguo Ji;Ying Zhao;Wei-Guo Zhu;Jianyuan Luo;Haiying Wang
p62是一种众所周知的自噬适配器，在响应各种应激时发挥多种功能。在这里，我们报告了一个功能的p62在碱基切除修复，是不同于其已知的功能。p62的缺失损害碱基切除修复能力，并增加癌细胞对烷化剂和氧化剂的敏感性。响应于烷基化和氧化损伤，p62在细胞核中积累，被hMOF乙酰化，并被SIRT7脱乙酰化，乙酰化的p62被募集到染色质。富含染色质的p62直接与BER途径的关键酶APE 1相互作用，并促进其核酸内切酶活性，从而促进BER和细胞存活。总的来说，我们的研究结果表明，p62是BER的调节因子，并为靶向p62作为癌症治疗策略提供了进一步的理论基础。
p62, a well-known adaptor of autophagy, plays multiple functions in response to various stresses. Here, we report a function for p62 in base excision repair that is distinct from its known functions. Loss of p62 impairs base excision repair capacity and increases the sensitivity of cancer cells to alkylating and oxidizing agents. In response to alkylative and oxidative damage, p62 is accumulated in the nucleus,acetylated by hMOF,and deacetylated by SIRT7, and acetylated p62 is recruited to chromatin. The chromatin-enriched p62 directly interacts with APE1, a key enzyme of the BER pathway, and promotes its endonuclease activity, which facilitates BER and cell survival. Collectively, our findings demonstrate that p62 is a regulator of BER and provide further rationale for targeting p62 as a cancer therapeutic strategy.