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GSK3B induces autophagy by phosphorylating ULK1

Title
GSK3B induces autophagy by phosphorylating ULK1
Authors
Ryu, Hye YoungKim, Eunjung LeahJeong, HyeonjeongYeo, Bo KyoungLee, Ji WonNam, HyeriHa, ShinwonAn, Hyun-KyuPark, HyunheeJung, SeongheeChung, Kyung MinKim, JiyeaLee, Byung-HoonCheong, HeesunKim, Eun-KyoungYu, Seong-Woon
DGIST Authors
Ryu, Hye Young; Kim, Eunjung Leah; Jeong, Hyeonjeong; Yeo, Bo Kyoung; Lee, Ji Won; Nam, Hyeri; Ha, Shinwon; An, Hyun-Kyu; Park, Hyunhee; Jung, Seonghee; Chung, Kyung Min; Kim, Jiyea; Lee, Byung-Hoon; Cheong, Heesun; Kim, Eun-KyoungYu, Seong-Woon
Issue Date
2021-03
Citation
Experimental and Molecular Medicine, 53(3), 369-383
Type
Article
ISSN
1226-3613
Abstract
Unc-51-like autophagy activating kinase 1 (ULK1), a mammalian homolog of the yeast kinase Atg1, has an essential role in autophagy induction. In nutrient and growth factor signaling, ULK1 activity is regulated by various posttranslational modifications, including phosphorylation, acetylation, and ubiquitination. We previously identified glycogen synthase kinase 3 beta (GSK3B) as an upstream regulator of insulin withdrawal-induced autophagy in adult hippocampal neural stem cells. Here, we report that following insulin withdrawal, GSK3B directly interacted with and activated ULK1 via phosphorylation of S405 and S415 within the GABARAP-interacting region. Phosphorylation of these residues facilitated the interaction of ULK1 with MAP1LC3B and GABARAPL1, while phosphorylation-defective mutants of ULK1 failed to do so and could not induce autophagy flux. Furthermore, high phosphorylation levels of ULK1 at S405 and S415 were observed in human pancreatic cancer cell lines, all of which are known to exhibit high levels of autophagy. Our results reveal the importance of GSK3B-mediated phosphorylation for ULK1 regulation and autophagy induction and potentially for tumorigenesis. © 2021, The Author(s).
URI
http://hdl.handle.net/20.500.11750/13865
DOI
10.1038/s12276-021-00570-6
Publisher
생화학분자생물학회
Related Researcher
  • Author Yu, Seong-Woon Laboratory of Neuronal Cell Death
  • Research Interests Molecular mechanisms of neuronal cell death and neurodegeneration
Files:
Collection:
ETC1. Journal Articles
Department of New BiologyLab of Protein Homeostasis and Drug Discovery1. Journal Articles
Department of Brain SciencesLab of Neuro-Metabolism & Neurometabolomic Research Center1. Journal Articles
Department of Brain SciencesLaboratory of Neuronal Cell Death1. Journal Articles


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