The deubiquitinating enzyme USP20 stabilizes ULK1 and promotes autophagy initiation

EMBO Reports
Jun Hwan KimSeok Hee Park

Abstract

Autophagy begins with the formation of autophagosomes, a process that depends on the activity of the serine/threonine kinase ULK1 (hATG1). Although earlier studies indicated that ULK1 activity is regulated by dynamic polyubiquitination, the deubiquitinase involved in the regulation of ULK1 remained unknown. In this study, we demonstrate that ubiquitin-specific protease 20 (USP20) acts as a positive regulator of autophagy initiation through stabilizing ULK1. At basal state, USP20 binds to and stabilizes ULK1 by removing the ubiquitin moiety, thereby interfering with the lysosomal degradation of ULK1. The stabilization of basal ULK1 protein levels is required for the initiation of starvation-induced autophagy, since the depletion of USP20 by RNA interference inhibits LC3 puncta formation, a marker of autophagic flux. At later stages of autophagy, USP20 dissociates from ULK1, resulting in enhanced ULK1 degradation and apoptosis. Taken together, our findings provide the first evidence that USP20 plays a crucial role in autophagy initiation by maintaining the basal expression level of ULK1.

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Citations

Mar 1, 2019·The Journal of Immunology : Official Journal of the American Association of Immunologists·Meng-Xin ZhangDandan Lin
May 2, 2020·International Journal of Molecular Sciences·Jihoon HaSeok Hee Park
Aug 22, 2018·Cells·Anne-Claire JacominMarie-Odile Fauvarque
Oct 3, 2020·Molecular Cancer·Tianshui SunQing Yang
Sep 6, 2020·Cells·Zhangyuan YinDaniel J Klionsky
Oct 22, 2019·Journal of Biomedical Science·Ruey-Hwa ChenTzu-Yu Huang
May 1, 2021·International Journal of Molecular Sciences·Choong-Sil LeeJaewhan Song
May 27, 2021·Trends in Endocrinology and Metabolism : TEM·Jia Liang Sun-WangAntonio Zorzano
Jul 29, 2021·Journal of Drug Targeting·Yingying LiGuangxi Zhai

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