Differential interactions between Beclin 1 and bcl-2 family members

被引:265
作者
Erlich, Shlomit
Mizrachy, Liat
Segev, Oshik
Lindenboim, Liora
Zmira, Ofir
Adi-Harel, Sheli
Hirsch, Joel A.
Stein, Reuven
Pinkas-Kramarski, Ronit [1 ]
机构
[1] Tel Aviv Univ, George S Wise Fac Life Sci, Dept Neurobiochem, IL-69978 Ramat Aviv, Israel
[2] Tel Aviv Univ, George S Wise Fac Life Sci, Dept Biochem, IL-69978 Ramat Aviv, Israel
关键词
Beclin; 1; autophagy; bcl-2; BH3-only; apoptosis;
D O I
10.4161/auto.4713
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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.
引用
收藏
页码:561 / 568
页数:8
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