A critical role for UVRAG in apoptosis

Xiaocheng Yin, Lizhi Cao, Yanhui Peng, Yanfang Tan, Min Xie, Rui Kang, Kristen M. Livesey, Daolin Tang

Research output: Contribution to journalArticle

18 Scopus citations

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 languageEnglish (US)
Pages (from-to)1242-1244
Number of pages3
JournalAutophagy
Volume7
Issue number10
DOIs
Publication statusPublished - Oct 2011
Externally publishedYes

    Fingerprint

Keywords

  • Apoptosis
  • Autophagy
  • Bax
  • Mitochondria
  • Tumor therapy
  • UVRAG

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Yin, X., Cao, L., Peng, Y., Tan, Y., Xie, M., Kang, R., ... Tang, D. (2011). A critical role for UVRAG in apoptosis. Autophagy, 7(10), 1242-1244. https://doi.org/10.4161/auto.7.10.16507