A nonautophagic role of ATG5 in regulating cell growth by targeting c-Myc for proteasome-mediated degradation.
A nonautophagic role of ATG5 in regulating cell growth by targeting c-Myc for proteasome-mediated degradation.
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ATG5 通过靶向 c-Myc 进行蛋白酶体介导的降解来调节细胞生长的非自噬作用
DOI：
10.1016/j.isci.2021.103296
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发表时间：
2021-11-19
期刊：
影响因子：
5.8
通讯作者：
Chen S
中科院分区：
文献类型：
--
作者：
Li S;Zhang L;Zhang G;Shangguan G;Hou X;Duan W;Xi Y;Xu N;Zhang B;Dong J;Wang Y;Cui W;Chen S
自噬是一种保守的生物过程，通过靶向大分子进行溶酶体介导的降解来维持细胞稳态。在正常条件下，自噬水平相对低于应激条件下（如饥饿），因为自噬通常在多次应激后被刺激。然而，在正常情况下，许多与自噬相关的调节因子仍然表达。尽管这些调节因子在自噬调节中已被深入研究，但这些调节因子在正常条件下的非自噬作用仍不完全清楚。在这里，我们发现自噬相关5 （autophagy-related 5, ATG5）是自噬的关键调节因子，在正常情况下通过泛素-蛋白酶体途径调节c-Myc蛋白降解。我们还发现ATG5结合c-Myc并招募E3泛素蛋白连接酶FBW7来促进c-Myc的降解。此外，atg5介导的c-Myc降解在正常条件下限制细胞生长，对胚胎干细胞分化至关重要。因此，本研究揭示了ATG5在调节c-Myc蛋白降解中的非自噬作用。ATG5在正常和饥饿条件下对细胞生长的差异调节ATG5招募FBW7在正常条件下调节c-Myc蛋白降解ATG5介导的c-Myc降解在正常条件下限制细胞生长ATG5在ESC分化过程中负调控c-Myc蛋白水平；细胞生物学的功能方面
Autophagy is a conserved biological process that maintains cell homeostasis by targeting macromolecules for lysosome-mediated degradation. The levels of autophagy are relatively lower under normal conditions than under stress conditions (e.g., starvation), as autophagy is usually stimulated after multiple stresses. However, many autophagy-related regulators are still expressed under normal conditions. Although these regulators have been studied deeply in autophagy regulation, the nonautophagic roles of these regulators under normal conditions remain incompletely understood. Here, we found that autophagy-related 5 (ATG5), which is a key regulator of autophagy, regulates c-Myc protein degradation under normal conditions through the ubiquitin-proteasome pathway. We also found that ATG5 binds c-Myc and recruits the E3 ubiquitin-protein ligase FBW7 to promote c-Myc degradation. Moreover, ATG5-mediated degradation of c-Myc limits cell growth under normal conditions and is essential for embryonic stem cell differentiation. Therefore, this study reveals a nonautophagic role of ATG5 in regulating of c-Myc protein degradation. ATG5 differentially regulates cell growth between normal and starvation conditions ATG5 recruits FBW7 to regulate c-Myc protein degradation under normal conditions ATG5-mediated degradation of c-Myc limits cell growth under normal conditions ATG5 negatively regulates the protein level of c-Myc during ESC differentiation Cell biology; Functional aspects of cell biology
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影响因子：
7.3
作者：
Pradel B;Robert-Hebmann V;Espert L
通讯作者：
Espert L
DOI：
10.1083/jcb.201403009
发表时间：
2014-07-21
期刊：
The Journal of cell biology
影响因子：
--
作者：
Chen R;Zou Y;Mao D;Sun D;Gao G;Shi J;Liu X;Zhu C;Yang M;Ye W;Hao Q;Li R;Yu L
通讯作者：
Yu L
H2B 单泛素化对 Warburg 效应的表观遗传调控
影响因子：
12.4
作者：
Jing, Yuan-Ya;Cai, Feng-Feng;Chen, Su
通讯作者：
Chen, Su
影响因子：
16
作者：
Kroemer G;Mariño G;Levine B
通讯作者：
Levine B
影响因子：
11.4
作者：
Shintani, T;Mizushima, N;Ohsumi, Y
通讯作者：
Ohsumi, Y