文献类型：期刊文献

英文题名：A fine-tuning mechanism underlying self-control for autophagy: deSUMOylation of BECN1 by SENP3

作者：Liu, Kejia[1];Guo, Chu[1];Lao, Yimin[1];Yangb, Jie[2];Chen, Fei[1];Zhao, Yuzheng[3,4];Yang, Yi[3,5];Yang, Jie[1];Yi, Jing[1]

机构：[1]Shanghai Jiao Tong Univ, Shanghai Key Lab Tumor Microenvironm & Inflammat, Key Lab Cell Differentiat & Apoptosis,Sch Med, Chinese Minist Educ,Dept Biochem & Mol Cell Biol, Shanghai 200025, Peoples R China;[2]Shanghai Jiao Tong Univ, Electron Microscopy Core Facil, Sch Med, Shanghai, Peoples R China;[3]East China Univ Sci & Technol, Optogenet & Synthet Biol Interdisciplinary Res Ct, Shanghai Collaborat Innovat Ctr Biomfg Technol, State Key Lab Bioreactor Engn, Shanghai, Peoples R China;[4]East China Univ Sci & Technol, Sch Pharm, Shanghai Key Lab New Drug Design, Shanghai, Peoples R China;[5]Chinese Acad Sci, CAS Ctr Excellence Brain Sci, Shanghai Inst Biol Sci, Shanghai, Peoples R China

年份：2020

卷号：16

期号：6

起止页码：975

外文期刊名：AUTOPHAGY

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000535659100002)】；

基金：This work was supported by the Shanghai Municipal Science and Technology Commission [11DZ2260200, 16ZR1418400]; National Natural Science Foundation of China (NSFC) [31230037,31471263,31771522]; Innovation Research Team of High-level Local University in Shanghai.

语种：英文

外文关键词：Autophagy; BECN1; reactive oxygen species; SENP3; SUMOylation

摘要：The roles of SUMOylation and the related enzymes in autophagic regulation are unclear. Based on our previous studies that identified the SUMO2/3-specific peptidase SENP3 as an oxidative stress-responsive molecule, we investigated the correlation between SUMOylation and macroautophagy/autophagy. We found that Senp3(+/-) mice showed increased autophagy in the liver under basal and fasting conditions, compared to Senp3(+/+) mice. We constructed a liver-specific senp3 knockout mouse; these Senp3-deficient liver tissues showed increased autophagy as well. Autophagic flux was accelerated in hepatic and other cell lines following knockdown of SENP3, both before and after the cells underwent starvation in the form of the serum and amino acid deprivation. We demonstrated that BECN1/beclin 1, the core molecule of the BECN1-PIK3C3 complex, could be SUMO3-conjugated by PIAS3 predominantly at K380 and deSUMOylated by SENP3. The basal SUMOylation of BECN1 was increased upon cellular starvation, which enhanced autophagosome formation by facilitating BECN1 interaction with other complex components UVRAG, PIK3C3 and ATG14, thus promoting PIK3C3 activity. In contrast, SENP3 deSUMOylated BECN1, which impaired BECN1-PIK3C3 complex formation or stability to suppress the PIK3C3 activity. DeSUMOylation of BECN1 restrained autophagy induction under basal conditions and especially upon starvation when SENP3 had accumulated in response to the increased generation of reactive oxygen species. Thus, while reversible SUMOylation regulated the degree of autophagy, SENP3 provided an intrinsic overflow valve for fine-tuning autophagy induction.