ATG5型
PI3K/AKT/mTOR通路
激酶
程序性细胞死亡
饥饿
细胞凋亡
信号转导
蛋白激酶B
ATG12
作者
Yongjie Wei,Sophie Pattingre,Sangita C. Sinha,Michael C. Bassik,Beth Levine
出处
期刊:Molecular Cell
[Elsevier]
日期:2008-06-20
卷期号:30 (6): 678-688
被引量:1053
标识
DOI:10.1016/j.molcel.2008.06.001
摘要
Starvation induces autophagy to preserve cellular homeostasis in virtually all eukaryotic organisms. However, the mechanisms by which starvation induces autophagy are not completely understood. In mammalian cells, the antiapoptotic protein, Bcl-2, binds to Beclin 1 during nonstarvation conditions and inhibits its autophagy function. Here we show that starvation induces phosphorylation of cellular Bcl-2 at residues T69, S70, and S87 of the nonstructured loop; Bcl-2 dissociation from Beclin 1; and autophagy activation. In contrast, viral Bcl-2, which lacks the phosphorylation site-containing nonstructured loop, fails to dissociate from Beclin 1 during starvation. Furthermore, the stress-activated signaling molecule, c-Jun N-terminal protein kinase 1 (JNK1), but not JNK2, mediates starvation-induced Bcl-2 phosphorylation, Bcl-2 dissociation from Beclin 1, and autophagy activation. Together, our findings demonstrate that JNK1-mediated multisite phosphorylation of Bcl-2 stimulates starvation-induced autophagy by disrupting the Bcl-2/Beclin 1 complex. These findings define a mechanism that cells use to regulate autophagic activity in response to nutrient status.
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