期刊
AUTOPHAGY
卷 4, 期 5, 页码 600-606出版社
TAYLOR & FRANCIS INC
DOI: 10.4161/auto.6260
关键词
Bcl-2; Bcl-xL; BH3-only proteins; Beclin 1; autophagy; apoptosis
类别
The essential autophagy protein and haplo-insufficient tumor suppressor, Beclin 1, interacts with several cofactors (Ambral, Bif-1, UVRAG) to activate the lipid kinase Vps34, thereby inducing autophagy. In normal conditions, Beclin 1 is bound to and inhibited by Bcl-2 or the Bcl-2 homolog Bcl-X-L. This interaction involves a Bcl-2 homology 3 (BH3) domain in Beclin 1 and the BH3 binding groove of Bcl-2/Bcl-X-L. Other proteins containing BH3 domains, called BH3-only proteins, can competitively disrupt the interaction between Beclin 1 and Bcl-2/Bcl-X-L to induce autophagy. Nutrient starvation, which is a potent physiologic inducer of autophagy, can stimulate the dissociation of Beclin 1 from its inhibitors, either by activating BH3-only proteins (such as Bad) or by posttranslational modifications of Bcl-2 (such as phosphorylation) that may reduce its affinity for Beclin l and BH3-only proteins. Thus, anti-apoptotic Bcl-2 family members and pro-apoptotic BH3-only proteins may participate in the inhibition and induction of autophagy, respectively: This hitherto neglected crosstalk between the core machineries regulating autophagy and apoptosis may redefine the role of Bcl-2 family proteins in oncogenesis and tumor progression.
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