A critical role for UVRAG in apoptosis

被引：36

作者：

Yin, Xiaocheng ^{[1
]}

Cao, Lizhi ^{[2
]}

Peng, Yanhui ^{[1
]}

Tan, Yanfang ^{[1
]}

Xie, Min ^{[2
]}

Kang, Rui ^{[2
,3
]}

Livesey, Kristen M. ^{[3
]}

Tang, Daolin ^{[3
]}

机构：

[1] Nanhua Univ, Affiliated Hosp 1, Dept Pediat, Hengyang, Peoples R China

[2] Cent S Univ, Xiangya Hosp, Changsha, Hunan, Peoples R China

[3] Univ Pittsburgh, Hillman Canc Ctr, Inst Canc, Pittsburgh, PA USA

来源：

AUTOPHAGY | 2011年 / 7卷 / 10期

关键词：

UVRAG; Bax; apoptosis; autophagy; mitochondria; tumor therapy;

D O I：

10.4161/auto.7.10.16507

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Autophagy and apoptosis are tightly regulated biological processes that are crucial for cell growth, development and tissue homeostasis. UVRAG (UV radiation resistance-associated gene), a mammalian homolog of yeast Vps38, activates the Beclin 1/PtdIns3KC3 (class III phosphatidylinositol-3-kinase) complex, which promotes autophagosome formation. Moreover, UVRAG promotes autophagosome maturation by recruiting class C Vps complexes (HOPS complexes) and Rab7 of the late endosome. We found that UVRAG has anti-apoptotic activity during tumor therapy through interactions with Bax. UVRAG inhibits Bax translocation from the cytosol to mitochondria during chemotherapy-or UV irradiation-induced apoptosis of human tumor cells. Moreover, deletion of the UVRAG C2 domain abolishes Bax binding and anti-apoptotic activity. These results suggest that, in addition to its previously recognized pro-autophagy activity in response to starvation, UVRAG has cytoprotective functions in the cytosol that control the localization of Bax in tumor cells exposed to apoptotic stimuli.

引用

页码：1242 / 1244

页数：3