期刊
SCIENCE
卷 338, 期 6109, 页码 956-959出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.1225967
关键词
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资金
- NIH/National Cancer Institute [ROI CA84254-S1, RO1 CA109618, ROI CA129451, KO8 CA164047]
- Dermatology Foundation Career Development Award
- Burroughs Wellcome Fund Career Award for Medical Scientists
- German Research Foundation [RE2673/1-1]
Aberrant signaling through the class I phosphatidylinositol 3-kinase (PI3K)-Akt axis is frequent in human cancer. Here, we show that Beclin 1, an essential autophagy and tumor suppressor protein, is a target of the protein kinase Akt. Expression of a Beclin 1 mutant resistant to Akt-mediated phosphorylation increased autophagy, reduced anchorage-independent growth, and inhibited Akt-driven tumorigenesis. Akt-mediated phosphorylation of Beclin 1 enhanced its interactions with 14-3-3 and vimentin intermediate filament proteins, and vimentin depletion increased autophagy and inhibited Akt-driven transformation. Thus, Akt-mediated phosphorylation of Beclin 1 functions in autophagy inhibition, oncogenesis, and the formation of an autophagy-inhibitory Beclin 1/14-3-3/vimentin intermediate filament complex. These findings have broad implications for understanding the role of Akt signaling and intermediate filament proteins in autophagy and cancer.
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