UV irradiation resistance-associated gene suppresses apoptosis by interfering with BAX activation

Xiaocheng Yin, Lizhi Cao, Rui Kang, Minghua Yang, Zhuo Wang, Yanhui Peng, Yanfang Tan, Liying Liu, Min Xie, Yiming Zhao, Kristen M. Livesey, Daolin Tang

Research output: Contribution to journalArticle

42 Scopus citations

Abstract

Ultraviolet irradiation resistance-associated gene (UVRAG) is a well-known regulator of autophagy by promoting autophagosome formation and maturation. However, little is known about the non-autophagic functions of UVRAG. Here, we present evidence that UVRAG functions as an unusual BCL2-associated X protein (Bax) suppressor to regulate apoptosis. Chemotherapy and radiation induces UVRAG expression and subsequently upregulates autophagy and apoptosis in tumour cells. Depletion of UVRAG expression by RNA interference renders tumour cells more sensitive to chemotherapy- and radiation-induced apoptosis in vitro and in vivo. Moreover, UVRAG interacts with Bax, which inhibits apoptotic stimuli-induced mitochondrial translocation of Bax, reduction of mitochondrial membrane potential, cytochrome c release and activation of caspase-9 and-3. Our findings show that UVRAG has an essential role in the intrinsic mitochondrial pathway of apoptosis by regulating the localization of Bax. This pathway represents a target for clinical intervention against tumours.

Original languageEnglish (US)
Pages (from-to)727-734
Number of pages8
JournalEMBO Reports
Volume12
Issue number7
DOIs
StatePublished - Jul 1 2011

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Keywords

  • BAX
  • apoptosis
  • autophagy
  • mitochondria

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Genetics

Cite this

Yin, X., Cao, L., Kang, R., Yang, M., Wang, Z., Peng, Y., Tan, Y., Liu, L., Xie, M., Zhao, Y., Livesey, K. M., & Tang, D. (2011). UV irradiation resistance-associated gene suppresses apoptosis by interfering with BAX activation. EMBO Reports, 12(7), 727-734. https://doi.org/10.1038/embor.2011.79