Title: ULK1 induces autophagy by phosphorylating Beclin-1 and activating VPS34 lipid kinase.

Authors: Russell, Ryan C; Tian, Ye; Yuan, Haixin; Park, Hyun Woo; Chang, Yu-Yun; Kim, Joungmok; Kim, Haerin; Neufeld, Thomas P; Dillin, Andrew; Guan, Kun-Liang

Published In Nat Cell Biol, (2013 Jul)

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.

PubMed ID: 23685627

MeSH Terms: Amino Acids/deficiency; Animals; Apoptosis Regulatory Proteins/metabolism*; Autophagy*; Autophagy-Related Protein-1 Homolog; Autophagy-Related Proteins; Beclin-1; Caenorhabditis elegans; Cells, Cultured; Class III Phosphatidylinositol 3-Kinases/metabolism*; Embryo, Mammalian/cytology; Embryo, Mammalian/metabolism*; Enzyme Activation; Fibroblasts/cytology; Fibroblasts/metabolism*; Humans; Intracellular Signaling Peptides and Proteins/metabolism; Kidney/cytology; Kidney/metabolism; Mice; Mice, Knockout; Phosphorylation; Protein Serine-Threonine Kinases/physiology*; Serine/metabolism; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Starvation; TOR Serine-Threonine Kinases/metabolism; Tumor Suppressor Proteins/metabolism; Vesicular Transport Proteins/metabolism