Beclin 1-independent autophagy induced by a Bcl-XL/Bcl-2 targeting compound, Z18

被引：64

作者：

Tian, Songhai ^{[4
,5
]}

Lin, Jian ^{[4
,5
]}

Zhou, Jun ^{[4
,5
]}

Wang, Xiaolong ^{[4
,5
]}

Li, Yanjun ^{[4
,5
]}

Ren, Xiaobai ^{[4
,5
]}

Yu, Wenyu ^{[4
,5
]}

Zhong, Wu ^{[1
]}

Xiao, Junhai ^{[1
]}

Sheng, Fugeng ^{[2
]}

Chen, Yingyu ^{[3
]}

Jin, Changwen ^{[4
,5
]}

Li, Song ^{[1
]}

Zheng, Zhibing ^{[1
]}

Xia, Bin ^{[4
,5
]}

机构：

[1] Beijing Inst Pharmacol & Toxicol, Beijing, Peoples R China

[2] Acad Mil Med Sci, Affiliated Hosp, Dept Radiol, Beijing, Peoples R China

[3] Peking Univ, Ctr Human Dis Genom, Beijing 100871, Peoples R China

[4] Beijing Nucl Magnet Resonance Ctr, Coll Chem & Mol Engn, Beijing, Peoples R China

[5] Beijing Nucl Magnet Resonance Ctr, Coll Life Sci, Beijing, Peoples R China

来源：

AUTOPHAGY | 2010年 / 6卷 / 08期

基金：

美国国家科学基金会;

关键词：

Z18; Bcl-X-L/Bcl-2; inhibitor; Beclin 1-independent autophagy; non-canonical autophagy; cell death; autophagosome accumulation; autophagic flux; BCL-X-L; CELL-DEATH; CANCER-CELLS; APOPTOSIS; PROTEIN; COMPLEX; DOMAIN;

D O I：

10.4161/auto.6.8.13336

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Inhibitors of Bcl-X-L/Bcl-2 can induce autophagy by releasing the autophagic protein Beclin 1 from its complexes with these proteins. Here we report a novel compound targeting the BH3 binding groove of Bcl-X-L/Bcl-2, Z18, which efficiently induces autophagy-associated cell death in HeLa cells, without apparent apoptosis. Unexpectedly, the inhibition of Beclin 1 and phosphatidylinositol 3-kinase have no obvious effect on Z18-induced autophagy in HeLa cells, implying that it is a non-canonical Beclin 1-independent autophagy. Meanwhile, the accumulation of autophagosomes is positively correlated with Z18-induced cell death and the full flux of autophagy is not necessary.

引用

页码：1032 / 1041

页数：10

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