• intestinal cancer

In humans, there is evidence that loss of the gene UVRAG contributes to the development of some forms of colorectal cancer. UVRAG (UV radiation resistance-associated gene) encodes a protein involved in regulation of different cellular pathways implicated in membrane trafficking; it has been shown to promote autophagy via interaction with the Beclin1-PI(3)KC3 complex. There is a single orthologous gene in Drosophila, Dmel\Uvrag, for which RNAi-targeting constructs, alleles caused by insertional mutagenesis, and loss-of-function alleles caused by imprecise excision of TE insertion(s) have been generated.

The human UVRAG gene has not been introduced into flies.

Animals homozygous for loss-of-function mutations of Uvrag die during the larval stage. Somatic clones in later stages exhibit neuroanatomy defects. Targeted knockdown of Uvrag in adult intestinal stem cells via RNAi results in overproliferation and impaired differentiation of the cells, without preventing autophagy. Other phenotypes observed include cell shape changes, gut dysfunction, and shortened lifespan. A small number of genetic and physical interactions of Dmel\Uvrag have been described; see below and in the Uvrag gene report.

Experiments in Drosophila suggest that it is endocytic function of Uvrag/UVRAG, not the autophagic function, that is important for preventing intestinal dysplasia.

[updated Jul. 2018 by FlyBase; FBrf0222196]