BAX and BAK1 are dispensable for ABT-737-induced dissociation of the BCL2-BECN1 complex and autophagy

被引：93

作者：

Bravo-San Pedro, Jose Manuel ^{[1
,2
,3
,4
,5
]}

Wei, Yongjie ^{[5
]}

Sica, Valentina ^{[1
,2
,3
,4
,5
]}

Maiuri, Maria Chiara ^{[1
,2
,3
,4
,5
]}

Zou, Zhongju ^{[6
,7
]}

Kroemer, Guido ^{[1
,2
,3
,5
,8
]}

Levine, Beth ^{[6
,7
]}

机构：

[1] Ctr Rech Cordeliers, Equipe Labellisee Ligue Natl Canc 11, Paris, France

[2] INSERM, U1138, Paris, France

[3] Univ Paris 05, Sorbonne Paris Cite, Paris, France

[4] Gustave Roussy Canc Campus, Villejuif, France

[5] Metabol & Cell Biol Platforms, Villejuif, France

[6] Univ Texas SW Med Ctr Dallas, Ctr Autophagy Res, Dept Internal Med, Dallas, TX 75390 USA

[7] Univ Texas SW Med Ctr Dallas, Howard Hughes Med Inst, Dallas, TX 75390 USA

[8] Hop Europeen Georges Pompidou, AP HP, Pole Biol, Paris, France

来源：

AUTOPHAGY | 2015年 / 11卷 / 03期

基金：

欧洲研究理事会;

关键词：

ABT-737; apoptosis; autophagy; BAX; BAK1; BCL2; BECN1 (Beclin 1); ACTB; actin; Baf A1; bafilomycin A(1); BCL2-antagonist; killer; 1; BCL2-associated X protein; B-cell CLL; lymphoma; 2; BECN1; Beclin; autophagy-related; DKO; double-knockout; FBS; fetal bovine serum; GAPDH; glyceraldehyde-3-phosphate dehydrogenase; HBSS; Hanks' balanced salt solution; HRP; horseradish peroxidase; MAP1LC3; LC3; microtubule-associated protein 1 light chain 3; MCL1; myeloid cell leukemia 1; MEFs; mouse embryonic fibroblasts; MTOR; mechanistic target of rapamycin; PBS; phosphate-buffered saline; SQSTM1; sequestosome; STS; staurosporine; WT; wild type; BCL-2; FAMILY-MEMBERS; BECLIN 1-DEPENDENT AUTOPHAGY; PHOSPHORYLATION; BH3-ONLY PROTEIN; MOLECULAR-BASIS; BH3; DOMAIN; X-L; APOPTOSIS; SUPPRESSION; PEPTIDE;

D O I：

10.1080/15548627.2015.1017191

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Disruption of the complex of BECN1 with BCL2 or BCL2L1/BCL-X-L is an essential switch that turns on cellular autophagy in response to environmental stress or treatment with BH3 peptidomimetics. Recently, it has been proposed that BCL2 and BCL2L1/BCL-X-L may inhibit autophagy indirectly through a mechanism dependent on the proapoptotic BCL2 family members, BAX and BAK1. Here we report that the BH3 mimetic, ABT-737, induces autophagy in parallel with disruption of BCL2-BECN1 binding in 2 different apoptosis-deficient cell types lacking BAX and BAK1, namely in mouse embryonic fibroblasts cells and in human colon cancer HCT116 cells. We conclude that the BH3 mimetic ABT-737 induces autophagy through a BAX and BAK1-independent mechanism that likely involves disruption of BECN1 binding to antiapoptotic BCL2 family members.

引用

页码：452 / 459

页数：8

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