P300/HDAC1 regulates the acetylation/deacetylation and autophagic activities of LC3/Atg8-PE ubiquitin-like system

文献类型： 外文期刊

第一作者： Wu, Wenmei

作者： Wu, Wenmei;Guo, Sanyou;Xu, Jing;Ma, Qiuqin;Li, Shuyan;Xu, Xianying;Huang, Zhijun;Zhong, Yangjin;Tian, Ling;Wu, Wenmei;Guo, Sanyou;Xu, Jing;Ma, Qiuqin;Li, Shuyan;Xu, Xianying;Huang, Zhijun;Zhong, Yangjin;Tian, Ling;Li, Kang;Li, Sheng;Tettamanti, Gianluca;Tettamanti, Gianluca;Cao, Yang;Cao, Yang

作者机构：

期刊名称：CELL DEATH DISCOVERY （ 影响因子：5.241； 五年影响因子：5.302 ）

ISSN：

年卷期： 2021 年 7 卷 1 期

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收录情况： SCI

摘要： Protein acetylation plays potential roles in regulating autophagy occurrence. However, it varies greatly between yeast and mammals, and has not been thoroughly investigated in other organisms. Here, we reported that the components of BmAtg8-PE ubiquitin-like system (BmAtg3, BmAtg4, BmAtg7, and BmAtg8) in Bombyx mori were localized in the nucleus under nutrient-rich conditions, whereas they were exported to the cytoplasm upon autophagy induction. RNAi of BmP300 and inhibition of BmP300 activity resulted in nucleo-cytoplasmic translocation of BmAtg3 and BmAtg8, as well as premature induction of autophagy in the absence of stimulus. Conversely, RNAi of BmHDAC1 and inhibition of class I/II HADCs activities led to the nuclear accumulation of BmAtg3 and BmAtg8. In addition, acetylation sites in Atg proteins of BmAtg8-PE ubiquitin-like system were identified by mass spectrometry, and acetylation-site mutations caused nucleo-cytoplasmic translocation of BmAtg3, BmAtg4, and BmAtg8 along with autophagy promotion. Similarly, the subcellular localization of human ATG4b is determined by acetylation modification. In general, BmP300-mediated acetylation sequesters the components of BmAtg8-PE ubiquitin-like system in the nucleus, thus leading to the autophagy inhibition. Oppositely, BmHDAC1-mediated deacetylation leads to the nucleo-cytoplasmic translocation of the components of BmAtg8-PE ubiquitin-like system and promotes autophagy. This process is evolutionarily conserved between insects and mammals.

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