GSK3B induces autophagy by phosphorylating ULK1

Hye Young Ryu, Leah Eunjung Kim, Hyeonjeong Jeong, Bo Kyoung Yeo, Ji-Won Lee, Hyeri Nam, Shinwon Ha, Hyun-Kyu An, Hyunhee Park, Seonghee Jung, Kyung Min Chung, Jiyea Kim, Byung-Hoon Lee, Heesun Cheong, Eun-Kyoung Kim, Seong-Woon Yu*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)
4 Downloads (Pure)

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.
Original languageEnglish
Pages (from-to)369-383
Number of pages15
JournalExperimental and Molecular Medicine
Volume53
Issue number3
DOIs
Publication statusPublished - 2 Mar 2021
Externally publishedYes

Bibliographical note

Copyright the Author(s) 2021. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

Fingerprint

Dive into the research topics of 'GSK3B induces autophagy by phosphorylating ULK1'. Together they form a unique fingerprint.

Cite this