A nonautophagic role of ATG5 in regulating cell growth by targeting c-Myc for proteasome-mediated degradation

Summary: 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...

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Autores principales:	Sheng Li, Leilei Zhang, Guoan Zhang, Guoqiang Shangguan, Xitan Hou, Wanglin Duan, Yan Xi, Nan Xu, Bowen Zhang, Junli Dong, Yequan Wang, Wen Cui, Su Chen
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	Cell biology Functional aspects of cell biology Science Q
Acceso en línea:	https://doaj.org/article/3a32599fc2db4c808e43e815bbe72b05
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spelling	oai:doaj.org-article:3a32599fc2db4c808e43e815bbe72b052021-11-20T05:09:34ZA nonautophagic role of ATG5 in regulating cell growth by targeting c-Myc for proteasome-mediated degradation2589-004210.1016/j.isci.2021.103296https://doaj.org/article/3a32599fc2db4c808e43e815bbe72b052021-11-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2589004221012657https://doaj.org/toc/2589-0042Summary: 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.Sheng LiLeilei ZhangGuoan ZhangGuoqiang ShangguanXitan HouWanglin DuanYan XiNan XuBowen ZhangJunli DongYequan WangWen CuiSu ChenElsevierarticleCell biologyFunctional aspects of cell biologyScienceQENiScience, Vol 24, Iss 11, Pp 103296- (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Cell biology Functional aspects of cell biology Science Q
spellingShingle	Cell biology Functional aspects of cell biology Science Q Sheng Li Leilei Zhang Guoan Zhang Guoqiang Shangguan Xitan Hou Wanglin Duan Yan Xi Nan Xu Bowen Zhang Junli Dong Yequan Wang Wen Cui Su Chen A nonautophagic role of ATG5 in regulating cell growth by targeting c-Myc for proteasome-mediated degradation
description	Summary: 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.
format	article
author	Sheng Li Leilei Zhang Guoan Zhang Guoqiang Shangguan Xitan Hou Wanglin Duan Yan Xi Nan Xu Bowen Zhang Junli Dong Yequan Wang Wen Cui Su Chen
author_facet	Sheng Li Leilei Zhang Guoan Zhang Guoqiang Shangguan Xitan Hou Wanglin Duan Yan Xi Nan Xu Bowen Zhang Junli Dong Yequan Wang Wen Cui Su Chen
author_sort	Sheng Li
title	A nonautophagic role of ATG5 in regulating cell growth by targeting c-Myc for proteasome-mediated degradation
title_short	A nonautophagic role of ATG5 in regulating cell growth by targeting c-Myc for proteasome-mediated degradation
title_full	A nonautophagic role of ATG5 in regulating cell growth by targeting c-Myc for proteasome-mediated degradation
title_fullStr	A nonautophagic role of ATG5 in regulating cell growth by targeting c-Myc for proteasome-mediated degradation
title_full_unstemmed	A nonautophagic role of ATG5 in regulating cell growth by targeting c-Myc for proteasome-mediated degradation
title_sort	nonautophagic role of atg5 in regulating cell growth by targeting c-myc for proteasome-mediated degradation
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/3a32599fc2db4c808e43e815bbe72b05
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A nonautophagic role of ATG5 in regulating cell growth by targeting c-Myc for proteasome-mediated degradation

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