USP20 deubiquitinates and stabilizes the ER-phagy receptor FAM134B to drive ER-phagy

doi:10.1101/2023.07.27.550606

	USP20 deubiquitinates and stabilizes the ER-phagy receptor FAM134B to drive ER-phagy
	Man, Zhang; Wang, Zhangshun; Zhao, Qing; Yang, Qian; Yang, Cuiwei; Liu, Yanfen
	2023-07-28
状态	已发表
摘要	The endoplasmic reticulum (ER) serves as a hub for various essential cellular processes, and maintaining ER homeostasis is essential for cell function. ER-phagy is a selective process that removes impaired ER subdomains through autophagosomes and lysosomal degradation. While the involvement of ubiquitination in autophagy regulation is well-established, its role in ER-phagy remains unclear. In our study, we screened deubiquitinating enzymes involved in ER-phagy and identified USP20 (ubiquitin specific peptidase 20) as a key regulator of ER-phagy under stress conditions. USP20 specifically cleaves K63 and K48 ubiquitin chains on the ER-phagy receptor FAM134B/RETREG1 (reticulophagy regulator 1), thereby stabilizing the substrate and promoting ER-phagy. Remarkably, despite lacking a transmembrane domain, USP20 is recruited to the ER through its interaction with VAPs (vesicle-associated membrane proteins). VAPs facilitate the recruitment of early autophagy proteins, including WIPI2, to specific ER subdomains, where USP20 and FAM134B are enriched. This recruitment of WIPI2 and other proteins plays a crucial role in facilitating FAM134B-mediated ER-phagy in response to cellular stress. Our findings highlight the critical role of USP20 in maintaining ER homeostasis by deubiquitinating and stabilizing FAM134B at distinct ER subdomains, where USP20 further recruits VAPs and promotes efficient ER-phagy.
关键词	deubiquitination ER-phagy FAM134B LC3 USP20 VAPs
语种	英语
DOI	10.1101/2023.07.27.550606
相关网址	查看原文
出处	bioRxiv
收录类别	PPRN.PPRN
WOS记录号	PPRN:74128328
WOS类目	Biochemistry & Molecular Biology
资助项目	National Natural Science Foundation of China["2015F0202-000","32070697"] ; ShanghaiTech University start-up fund[31570781]
文献类型	预印本
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/381344
专题	生命科学与技术学院生命科学与技术学院_PI研究组_刘艳芬组生命科学与技术学院_博士生
通讯作者	Liu, Yanfen
作者单位	ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China
推荐引用方式 GB/T 7714	Man, Zhang,Wang, Zhangshun,Zhao, Qing,et al. USP20 deubiquitinates and stabilizes the ER-phagy receptor FAM134B to drive ER-phagy. 2023.