Background
Autophagy is a catabolic process for the autophagosomic-lysosomal degradation of bulk cytoplasmic contents. It is generally activated by conditions of nutrient deprivation but has also been associated with a number of physiological processes including development, differentiation, neurodegeneration, infection and cancer. The molecular machinery of autophagy was largely discovered in yeast and referred to as autophagy-related (Atg) genes. These proteins are involved in the formation of cytoplasmic vacuoles called autophagosomes that are delivered to lysosomes for degradation.The class III type phosphoinositide 3-kinase (PI3KC3)/Vps34 regulates vacuolar trafficking as well as autophagy. Multiple proteins have been shown to be associated with Vsp34, including: p105/Vsp15, Beclin-1, UVRAG, Atg14, and Rubicon, which can determine Vsp34 function. UVRAG (UV radiation resistance-associated gene) is associated with the Beclin-1/PI3KC3 complex and promotes PI3KC3 enzymatic activity and autophagy, while suppressing proliferation. Beclin-1 binding to UVRAG promotes both autophagosome maturation and endocytic trafficking. UVRAG is also a potential tumor suppressor protein with frameshift mutations observed in colon and gastric carcinomas.