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The deubiquitinating enzyme USP20 stabilizes ULK1 and promotes autophagy initiation.
Kim, Jun Hwan; Seo, Dongyeob; Kim, Sun-Jick; Choi, Dong Wook; Park, Jin Seok; Ha, Jihoon; Choi, Jungwon; Lee, Ji-Hyung; Jung, Su Myung; Seo, Kyoung-Wan; Lee, Eun-Woo; Lee, Youn Sook; Cheong, Heesun; Choi, Cheol Yong; Park, Seok Hee.
Afiliación
  • Kim JH; Department of Biological Sciences, Sungkyunkwan University, Suwon, Korea.
  • Seo D; Department of Biological Sciences, Sungkyunkwan University, Suwon, Korea.
  • Kim SJ; Department of Biological Sciences, Sungkyunkwan University, Suwon, Korea.
  • Choi DW; Department of Biological Sciences, Sungkyunkwan University, Suwon, Korea.
  • Park JS; Department of Biological Sciences, Sungkyunkwan University, Suwon, Korea.
  • Ha J; Department of Biological Sciences, Sungkyunkwan University, Suwon, Korea.
  • Choi J; Division of Cancer Biology, Research Institute, National Cancer Center, Goyang, Korea.
  • Lee JH; Department of Biological Sciences, Sungkyunkwan University, Suwon, Korea.
  • Jung SM; Department of Biological Sciences, Sungkyunkwan University, Suwon, Korea.
  • Seo KW; Department of Biological Sciences, Sungkyunkwan University, Suwon, Korea.
  • Lee EW; Division of Biomedical Science, Korea Research Institute of Bioscience & Biotechnology, Daejeon, Korea.
  • Lee YS; Department of Biological Sciences, Sungkyunkwan University, Suwon, Korea.
  • Cheong H; Division of Cancer Biology, Research Institute, National Cancer Center, Goyang, Korea.
  • Choi CY; Department of Biological Sciences, Sungkyunkwan University, Suwon, Korea choicy@skku.ac.kr parks@skku.edu.
  • Park SH; Department of Biological Sciences, Sungkyunkwan University, Suwon, Korea choicy@skku.ac.kr parks@skku.edu.
EMBO Rep ; 19(4)2018 04.
Article en En | MEDLINE | ID: mdl-29487085
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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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Autofagia / Ubiquitina Tiolesterasa / Homólogo de la Proteína 1 Relacionada con la Autofagia Límite: Animals / Humans Idioma: En Revista: EMBO Rep Asunto de la revista: BIOLOGIA MOLECULAR Año: 2018 Tipo del documento: Article

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Autofagia / Ubiquitina Tiolesterasa / Homólogo de la Proteína 1 Relacionada con la Autofagia Límite: Animals / Humans Idioma: En Revista: EMBO Rep Asunto de la revista: BIOLOGIA MOLECULAR Año: 2018 Tipo del documento: Article