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.
Original language | English (US) |
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Pages (from-to) | 1242-1244 |
Number of pages | 3 |
Journal | Autophagy |
Volume | 7 |
Issue number | 10 |
DOIs | |
State | Published - Oct 2011 |
Externally published | Yes |
Keywords
- Apoptosis
- Autophagy
- Bax
- Mitochondria
- Tumor therapy
- UVRAG
ASJC Scopus subject areas
- Molecular Biology
- Cell Biology