A critical role for UVRAG in apoptosis

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) co...

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Bibliographic Details
Published in:Autophagy 2011-10, Vol.7 (10), p.1242-1244
Main Authors: Yin, Xiaocheng, Cao, Lizhi, Peng, Yanhui, Tan, Yanfang, Xie, Min, Kang, Rui, Livesey, Kristen M., Tang, Daolin
Format: Article
Language:English
Subjects:
Animals
Antineoplastic Agents - pharmacology
Apoptosis
Autophagic Punctum
Autophagy
bcl-2-Associated X Protein - metabolism
Binding
Biology
Bioscience
Calcium
Cancer
Cell
Cell Line, Tumor
Cycle
Cytosol - metabolism
Endosomes - metabolism
Humans
Landes
Mice
Mitochondria - metabolism
Models, Biological
Neoplasm Transplantation
Organogenesis
Proteins
Tumor Suppressor Proteins - physiology
Ultraviolet Rays
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Summary: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.
ISSN:1554-8627
1554-8635
DOI:10.4161/auto.7.10.16507