title: A critical role for UVRAG in apoptosis.
abstract: 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.
authors: Department of Pediatrics, The First Affiliated Hospital of Nanhua University, Hengyang, Hunan People's Republic of China. xcyin108@sina.com
authors: Xiaocheng
authors: X
authors: Yin
authors: Lizhi
authors: L
authors: Cao
authors: Yanhui
authors: Y
authors: Peng
authors: Yanfang
authors: Y
authors: Tan
authors: Min
authors: M
authors: Xie
authors: Rui
authors: R
authors: Kang
authors: Kristen M
authors: KM
authors: Livesey
authors: Daolin
authors: D
authors: Tang
references: EMBO Rep. 2011 Jul 01;12(7):727-34
references: 21597469