JNK1-Mediated Phosphorylation of Bcl-2 Regulates Starvation-Induced Autophagy

Yongjie Wei, Sophie Pattingre, Sangita Sinha, Michael Bassik, Beth Levine

Research output: Contribution to journalArticle

773 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)678-688
Number of pages11
JournalMolecular Cell
Volume30
Issue number6
DOIs
StatePublished - Jun 20 2008

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Mitogen-Activated Protein Kinase 8
Autophagy
Starvation
Phosphorylation
Proteins
Homeostasis
Beclin-1
Food

Keywords

  • CELLCYCLE
  • SIGNALING

ASJC Scopus subject areas

  • Molecular Biology

Cite this

JNK1-Mediated Phosphorylation of Bcl-2 Regulates Starvation-Induced Autophagy. / Wei, Yongjie; Pattingre, Sophie; Sinha, Sangita; Bassik, Michael; Levine, Beth.

In: Molecular Cell, Vol. 30, No. 6, 20.06.2008, p. 678-688.

Research output: Contribution to journalArticle

Wei, Yongjie ; Pattingre, Sophie ; Sinha, Sangita ; Bassik, Michael ; Levine, Beth. / JNK1-Mediated Phosphorylation of Bcl-2 Regulates Starvation-Induced Autophagy. In: Molecular Cell. 2008 ; Vol. 30, No. 6. pp. 678-688.
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