Differential Interactions Between Beclin 1 and Bcl-2 Family Members

• Published in: Autophagy Vol. 3; no. 6; pp. 561 - 568
• Main Authors: Erlich, Shlomit, Mizrachy, Liat, Segev, Oshik, Lindenboim, Liora, Zmira, Ofir, Adi-Harel, Sheli, Hirsch, Joel A., Stein, Reuven, Pinkas-Kramarski, Ronit
• Format: Journal Article
• Language: English
• Published: United States Taylor & Francis 01.11.2007
• Subjects: Amino Acid Sequence; Animals; Apoptosis; Apoptosis Regulatory Proteins - chemistry; Apoptosis Regulatory Proteins - genetics; Apoptosis Regulatory Proteins - metabolism; Autophagy; bcl-2-Associated X Protein - metabolism; bcl-X Protein - chemistry; bcl-X Protein - metabolism; Beclin-1; BH3 Interacting Domain Death Agonist Protein - metabolism; Binding; Biology; Bioscience; Calcium; Cancer; Cell; Cell Line; Cercopithecus aethiops; COS Cells; Cycle; Glutathione Transferase - metabolism; Humans; Kidney - cytology; Landes; Membrane Proteins - chemistry; Membrane Proteins - genetics; Membrane Proteins - metabolism; Models, Molecular; Molecular Sequence Data; Myeloid Cell Leukemia Sequence 1 Protein; Neoplasm Proteins - metabolism; Organogenesis; Plasmids; Protein Structure, Tertiary - genetics; Proteins; Proto-Oncogene Proteins c-bcl-2 - metabolism; Recombinant Fusion Proteins - chemistry; Recombinant Fusion Proteins - metabolism; Sequence Homology, Amino Acid; Transfection
• DOI: 10.4161/auto.4713
• ISSN: 1554-8627

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-x L , 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-x L 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-x L . Our results suggest that BH3 only proapoptotic Bcl-2 proteins may modulate the interactions between Bcl-x L and Beclin 1.