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Nat Cell Biol. 2013 Jul;15(7):741-50. doi: 10.1038/ncb2757. Epub 2013 May 19.

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

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Department of Pharmacology and Moores Cancer Center, University of California San Diego, La Jolla, California 92093, USA.


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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