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

被引：0
作者：
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
机构：
[1] University of California San Diego,Department of Pharmacology and Moores Cancer Center
[2] University of California Berkeley,Department of Molecular and Cell Biology
[3] Cell Biology and Development,Department of Genetics
[4] University of Minnesota,Department of Oral Biochemistry
[5] School of Dentistry,undefined
[6] Kyung Hee University,undefined
来源：
Nature Cell Biology | 2013年 / 15卷
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摘要：
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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页码：741 / 750
页数：9
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