P300/HDAC1 regulates the acetylation/deacetylation and autophagic activities of LC3/Atg8-PE ubiquitin-like system.
P300/HDAC1 regulates the acetylation/deacetylation and autophagic activities of LC3/Atg8-PE ubiquitin-like system.
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DOI：
10.1038/s41420-021-00513-0
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发表时间：
2021-05-31
影响因子：
7
通讯作者：
Tian L
中科院分区：
文献类型：
--
作者：
Wu W;Li K;Guo S;Xu J;Ma Q;Li S;Xu X;Huang Z;Zhong Y;Tettamanti G;Cao Y;Li S;Tian L
蛋白乙酰化在调节自噬发生中起潜在作用。然而，它在酵母和哺乳动物之间差异很大，并且尚未在其他生物体中进行彻底研究。在这里，我们报道了家蚕BmAtg3 - pe泛素样系统的成分（BmAtg3, BmAtg4， BmAtg7和BmAtg8）在营养丰富的条件下定位在细胞核中，而在自噬诱导下它们被输出到细胞质中。BmP300的RNAi和BmP300活性的抑制导致BmAtg3和BmAtg8的核胞质易位，以及在缺乏刺激的情况下过早诱导自噬。相反，BmHDAC1的RNAi和I/II类hadac活性的抑制导致BmAtg3和BmAtg8的核积累。此外，通过质谱法鉴定了BmAtg8 - pe泛素样系统Atg蛋白的乙酰化位点，乙酰化位点突变导致BmAtg3、BmAtg4和BmAtg8的核胞质易位，并促进自噬。类似地，人ATG4b的亚细胞定位是通过乙酰化修饰确定的。一般来说，bmp300介导的乙酰化会隔离细胞核中BmAtg8-PE泛素样系统的组分，从而导致自噬抑制。相反，bmhdac1介导的去乙酰化导致BmAtg8-PE泛素样系统组分的核-胞质易位，促进自噬。这一过程在昆虫和哺乳动物之间是进化保守的。
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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影响因子：
21.3
作者：
通讯作者：
--
影响因子：
64.8
作者：
Ichimura, Y;Kirisako, T;Ohsumi, Y
通讯作者：
Ohsumi, Y
DOI：
10.1111/febs.13356
发表时间：
2015-09
期刊：
The FEBS journal
影响因子：
--
作者：
Popelka H;Klionsky DJ
通讯作者：
Klionsky DJ
影响因子：
16.8
作者：
Kaiser, Stephen E.;Mao, Kai;Taherbhoy, Asad M.;Yu, Shanshan;Olszewski, Jennifer L.;Duda, David M.;Kurinov, Igor;Deng, Alan;Fenn, Timothy D.;Klionsky, Daniel J.;Schulman, Brenda A.
通讯作者：
Schulman, Brenda A.
DOI：
10.1073/pnas.0712145105
发表时间：
2008-03-04
影响因子：
11.1
作者：
Lee, In Hye;Cao, Liu;Finkel, Toren
通讯作者：
Finkel, Toren