Bcl-2 family members: Dual regulators of apoptosis and autophagy

Beth Levine, Sangita Sinha, Guido Kroemer

Research output: Contribution to journalReview articlepeer-review

602 Scopus citations

Abstract

The essential autophagy protein and haplo-insufficient tumor suppressor, Beclin 1, interacts with several cofactors (Ambrai, 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-XL. This interaction involves a Bcl-2 homology 3 (BH3) domain in Beclin 1 and the BH3 binding groove of Bcl-2/Bcl-XL. Other proteins containing BH3 domains, called BH3-only proteins, can competitively disrupt the interaction between Beclin 1 and Bcl-2/Bcl-XL 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 1 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.

Original languageEnglish (US)
Pages (from-to)600-606
Number of pages7
JournalAutophagy
Volume4
Issue number5
DOIs
StatePublished - Jul 1 2008

Keywords

  • Apoptosis
  • Autophagy
  • BH3-only proteins
  • Bcl-2
  • Bcl-xL
  • Beclin 1

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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