UV resistance-associated gene (UVRAG) is a tumor suppressor that is commonly mutated in colon and breast cancer. While UVRAG was discovered for its ability to complement UV sensitivity in xeroderma pigmentosum cells, its main functions are in autophagy, endocytosis, and apoptosis. During autophagy UVRAG interacts with Beclin 1 to promote autophagosome formation. UVRAG can also interact with VPS16 to recruit membrane fusion machinery to mediate autophagosome maturation. These interactions were studied in detail in a recent study by Sun et al. (1). They used UVRAG antibody in immunoprecipitation experiments to examine the effect of Beclin 1 acetylation on UVRAG-Beclin 1 complex assembly and autophagosome maturation (1). In addition to autophagy the Beclin 1-UVRAG interaction was also shown to be essential for endocytosis and neuron viability (2). McKnight et al. used UVRAG antibody to show UVRAG is destabilized in the absence of Beclin 1. Loss of Beclin 1 disrupted the UVRAG-VPS34 interaction, as shown through immunoprecipitation with the UVRAG antibody, leading to decreased VPS34 kinase activity and defects in endosome formation (2). The function of UVRAG-Beclin 1 complexes in neuronal cells may underlie the observations of reduced Beclin 1 expression in Alzheimer’s disease (3). UVRAG’s function in endocytosis is also important for virus entry. Pirooz et al. used immunoprecipitation with UVRAG antibody to characterize the interactions of UVRAG with membrane fusion machinery components that are important for virus entry (4). During apoptosis, UVRAG binds to and sequesters Bcl-2 associated X protein (BAX) to prevent its translocation to the mitochondrial membrane. Inhibition of apoptosis has important implications as UVRAG is upregulated by cancer cells following radiation and chemotherapy. The ability of UVRAG to protect cells from radiation may be through maintenance of genome stability. Disruption of the Beclin 1-UVRAG interaction resulted in increased DNA double-strand breaks as shown through immunoprecipitation and western blotting with the UVRAG antibody (5). These roles in cancer biology and in basic cellular processes like endocytosis make UVRAG an important target for further investigation.
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