Figure 1.

Conceptual relationships between UVRAG and apoptosis/autophagy. Tumor therapies, such as chemotherapy and radiation, increase UVRAG expression in tumor cells. Moreover, UVRAG forms two different complexes to regulate crosstalk between apoptosis and autophagy. On the one hand, UVRAG promotes autophagy through interactions with Beclin 1 via the CCD domain. Cdk5-mediated phosphorylation of Bif-1 interacts with the PR domain within UVRAG, which promotes formation of the Beclin 1/PtdIns3KC3 complex. Microtubule-associated protein 1 light chain 3 (LC3), a mammalian homolog of yeast Atg8, is the most widely-used marker of autophagosomes. During autophagy, LC3-I is converted to LC3-II. On the other hand, UVRAG binds directly to Bax in the cytosol through the C2 domain, which prevents Bax translocation to mitochondria and subsequent induction of apoptosis.