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Autophagy. 2011 Oct;7(10):1242-4. doi: 10.4161/auto.7.10.16507. Epub 2011 Oct 1.

A critical role for UVRAG in apoptosis.

Author information

1
Department of Pediatrics, The First Affiliated Hospital of Nanhua University, Hengyang, Hunan People's Republic of China. xcyin108@sina.com

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.

PMID:
21606679
PMCID:
PMC3210309
DOI:
10.4161/auto.7.10.16507
[Indexed for MEDLINE]
Free PMC Article

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