کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1997513 1541540 2008 11 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
JNK1-Mediated Phosphorylation of Bcl-2 Regulates Starvation-Induced Autophagy
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
JNK1-Mediated Phosphorylation of Bcl-2 Regulates Starvation-Induced Autophagy
چکیده انگلیسی

SummaryStarvation 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.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: - Volume 30, Issue 6, 20 June 2008, Pages 678–688
نویسندگان
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