The Beclin 1 network regulates autophagy and apoptosis

R. Kang, H. J. Zeh, M. T. Lotze, D. Tang

Research output: Contribution to journalReview article

1252 Scopus citations

Abstract

Beclin 1, the mammalian orthologue of yeast Atg6, has a central role in autophagy, a process of programmed cell survival, which is increased during periods of cell stress and extinguished during the cell cycle. It interacts with several cofactors (Atg14L, UVRAG, Bif-1, Rubicon, Ambra1, HMGB1, nPIST, VMP1, SLAM, IP3R, PINK and survivin) to regulate the lipid kinase Vps-34 protein and promote formation of Beclin 1-Vps34-Vps15 core complexes, thereby inducing autophagy. In contrast, the BH3 domain of Beclin 1 is bound to, and inhibited by Bcl-2 or Bcl-XL. This interaction can be disrupted by phosphorylation of Bcl-2 and Beclin 1, or ubiquitination of Beclin 1. Interestingly, caspase-mediated cleavage of Beclin 1 promotes crosstalk between apoptosis and autophagy. Beclin 1 dysfunction has been implicated in many disorders, including cancer and neurodegeneration. Here, we summarize new findings regarding the organization and function of the Beclin 1 network in cellular homeostasis, focusing on the cross-regulation between apoptosis and autophagy.

Original languageEnglish (US)
Pages (from-to)571-580
Number of pages10
JournalCell Death and Differentiation
Volume18
Issue number4
DOIs
StatePublished - Apr 1 2011
Externally publishedYes

Keywords

  • Bcl-2
  • Beclin 1
  • PI3K
  • apoptosis
  • autophagy
  • signal transduction

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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