Cleaving Beclin 1 to suppress autophagy in chemotherapy-induced apoptosis

被引：31

作者：

Li, Hua ^{[1
,2
]}

Wang, Peng ^{[1
,2
]}

Yu, Jian ^{[1
,3
]}

Zhang, Lin ^{[1
,2
]}

机构：

[1] Univ Pittsburgh, Inst Canc, Pittsburgh, PA 15260 USA

[2] Univ Pittsburgh, Sch Med, Dept Pharmacol & Chem Biol, Pittsburgh, PA USA

[3] Univ Pittsburgh, Sch Med, Dept Pathol, Pittsburgh, PA USA

来源：

AUTOPHAGY | 2011年 / 7卷 / 10期

关键词：

Beclin; 1; caspase; 8; autophagy; apoptosis; chemotherapy;

D O I：

10.4161/auto.7.10.16490

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Autophagy is often found in apoptosis-defective cancer cells and contributes to chemotherapy resistance. However, it is far from clear how the coordination of apoptosis and autophagy determines sensitivity of cancer cells to chemotherapy. Our recent study showed that Beclin 1, a key regulator of autophagy, is cleaved by caspase 8 at the execution stage of chemotherapy-induced and mitochondria-mediated apoptosis. Perturbation of Beclin 1 cleavage, by knock-in of a mutation, phenocopies the autophagy observed in apoptosis-defective cancer cells, and renders chemotherapy resistance in vitro and in vivo. These results demonstrate an important role of caspases in suppressing autophagy by cleaving autophagic machinery.

引用

页码：1239 / 1241

页数：3