Prostate cancer (PC) is one of the leading causes of cancer-related mortality in men; one in five men diagnosed with PC present an advanced or metastatic form of the disease1. Our laboratory has revealed that the expression of human papillomavirus E6-Associated Protein (E6AP) is elevated in a proportion of PC patients. This elevation, in associated with low promyelocytic leukemia protein levels, predicts poor prognosis2. Studies from our lab and others have previously revealed a role for E6AP in the control of cellular senescence and cell cycle arrest3, 4. To define the role of E6AP in PC, our laboratory investigated the impact of E6AP knockdown on PC cell growth. These studies revealed a role for E6AP in the growth and survival of PC cells and in their response to DNA damage (see the poster by Piotr Paul). However, the mechanisms by which E6AP regulates these processes in PC cells remain unknown.
To explore these mechanisms, we have chosen a proteomic approach. We will employ PC cell lines with an inducible knockdown of E6AP and changes in total proteome will be assessed. As E6AP is an E3 ubiquitin ligase, we will search for ubiquitinated targets of E6AP in PC cells under basal and stress conditions. The effect of E6AP knockdown during radiation-induced stress will also be examined. The protein targets derived from this project are anticipated to reveal the mechanism by which E6AP contributes to PC and as such may define novel therapeutic targets for PC.