HPV E6 degradation of p53 and PDZ containing substrates in an E6AP null background

Human papillomavirus (HPV) type 16 and 18 E6 proteins target many of their cellular substrates for proteasome-mediated degradation. In the case of p53, this is mediated by the E6AP ubiquitin ligase. However it is still unclear whether other E6 substrates, in particular those containing PDZ domains, are also degraded in a similar manner. To investigate this, we established an epithelial cell line from E6AP-null mice and used these cells as a background to perform E6-mediated in vivo degradation assays. We show that the PDZ domain-containing substrates of E6, including Scribble, MAGI-1 and MAGI-3, are all subject to E6-mediated degradation in these cells. Strikingly, we also found that p53 could be degraded by E6 within these cells in a proteasome-dependent manner. These results demonstrate that HPV-16 and -18 E6 can target substrates for degradation in a manner independent of the E6AP ubiquitin ligase.