A critical role for UVRAG in apoptosis

• 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
• ISSN: 1554-8627; 1554-8635
• DOI: 10.4161/auto.7.10.16507

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.