ULK1 Induces Autophagy by Phosphorylating Beclin-1 and Activating VPS34 Lipid Kinase

Overview

Journal Nat Cell Biol

Specialty Cell Biology

Date 2013 May 21

PMID 23685627

Citations 819

Authors

Ryan C Russell

Ye Tian

Haixin Yuan

Hyun Woo Park

Yu-Yun Chang

Joungmok Kim

Haerin Kim

Thomas P Neufeld

Andrew Dillin

Kun-Liang Guan

Affiliations

Soon will be listed here.

Abstract

Autophagy is the primary cellular catabolic program activated in response to nutrient starvation. Initiation of autophagy, particularly by amino-acid withdrawal, requires the ULK kinases. Despite its pivotal role in autophagy initiation, little is known about the mechanisms by which ULK promotes autophagy. Here we describe a molecular mechanism linking ULK to the pro-autophagic lipid kinase VPS34. Following amino-acid starvation or mTOR inhibition, the activated ULK1 phosphorylates Beclin-1 on Ser 14, thereby enhancing the activity of the ATG14L-containing VPS34 complexes. The Beclin-1 Ser 14 phosphorylation by ULK is required for full autophagic induction in mammals and this requirement is conserved in Caenorhabditis elegans. Our study reveals a molecular link from ULK1 to activation of the autophagy-specific VPS34 complex and autophagy induction.

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