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UV irradiation resistance-associated gene suppresses apoptosis by interfering with BAX activation.
- Source :
-
EMBO reports [EMBO Rep] 2011 Jul 01; Vol. 12 (7), pp. 727-34. Date of Electronic Publication: 2011 Jul 01. - Publication Year :
- 2011
-
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.
- Subjects :
- Animals
Cell Line, Tumor
Drug Resistance, Neoplasm genetics
HCT116 Cells
HL-60 Cells
HeLa Cells
Humans
Mice
Mice, Nude
Mitochondria metabolism
Mutagens pharmacology
Protein Binding physiology
Protein Transport genetics
Radiation Tolerance genetics
bcl-2-Associated X Protein genetics
Apoptosis genetics
Gene Expression Regulation, Neoplastic drug effects
Gene Expression Regulation, Neoplastic radiation effects
Tumor Suppressor Proteins genetics
Tumor Suppressor Proteins metabolism
Ultraviolet Rays
bcl-2-Associated X Protein metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1469-3178
- Volume :
- 12
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- EMBO reports
- Publication Type :
- Academic Journal
- Accession number :
- 21597469
- Full Text :
- https://doi.org/10.1038/embor.2011.79