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

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.

SUBMITTER: Yin X

PROVIDER: S-EPMC3128967 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:A fuller study of UV-induced biological effects lies beyond the scope of this paper. I will focus on the genetic interaction of cells irradiated by UV. Accordingly, in respect to genomic, the regulation of the gene expressions in cells represents how they response to the stress and repair themselves. In the past, Northern Blot has been used to detect the expression level of a few genes in one experiment. Thus, this assay is always limited to a small scope of a huge unknown network of gene expression. However, to investigate gene expression networks made of thousands of genes, a powerful tool must be implemented. As anticipated, the interactions between regulated genes in UV irradiation time-course experiment can be analyzed by cDNA microarray analysis with experimental loop design. This study provides a platform to investigate the gene networks regulated by UV irradiation. Keywords: UV, cDNA microarray, mitochondria respiratory chain, ROS, carcinogenesis

2006-11-17 | GSE3623 | GEO

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