Differential interactions between Beclin 1 and Bcl-2 family members

Shlomit Erlich, Liat Mizrachy, Oshik Segev, Liora Lindenboim, Ofir Zmira, Sheli Adi-Harel, Joel A. Hirsch, Reuven Stein, Ronit Pinkas-Kramarski

Research output: Contribution to journalArticlepeer-review

Abstract

Autophagy, a cellular degradation system, promotes both cell death and survival. The interaction between Bcl-2 family proteins and Beclin 1, a Bcl-2 interacting protein that promotes autophagy, can mediate crosstalk between autophagy and apoptosis. We investigated the interaction between anti-and pro-apoptotic Bcl-2 proteins with Beclin 1. Our results show that Beclin 1 directly interacts with Bcl-2, Bcl-xL, Bcl-w and to a lesser extent with Mcl-1. Beclin 1 does not bind the pro-apoptotic Bcl-2 proteins. The interaction between Beclin 1 and the anti-apoptotic protein Bcl-xL was inhibited by BH3-only proteins, but not by multi-domain proteins. Sequence alignment and structural modeling suggest that Beclin 1 contains a putative BH3-like domain which may interact with the hydrophobic grove of Bcl-x L. Mutation of the Beclin 1 amino acids predicted to mediate this interaction inhibited the association of Beclin 1 with Bcl-xL. Our results suggest that BH3 only proapoptotic Bcl-2 proteins may modulate the interactions between Bcl-xL and Beclin 1.

Original languageEnglish
Pages (from-to)561-568
Number of pages8
JournalAutophagy
Volume3
Issue number6
DOIs
StatePublished - 2007

Keywords

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

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