Oncogenic human papillomavirus E6 proteins target the discs large tumour suppressor for proteasome-mediated degradation

摘要: Previous studies have shown that the oncogenic HPV E6 proteins form a complex with human homologue of Drosophila tumour suppressor protein, discs large (Dlg). This is mediated by carboxy terminus and involves recognition at least one PDZ domain Dlg. region not conserved amongst from low risk papillomavirus types and, hence, binding to Dlg correlates potential these viruses. We performed investigate consequences interaction between Mutational analysis both HPV18 has further defined regions necessary for formation. Strikingly, co-expression wild type in vitro or vivo results dramatic decrease amount whereas mutants which fail minimal effect on protein levels. The HPV16 also decreased levels, but this was observed HPV11 protein. Moreover, within first 544 amino acids containing three domains confers susceptibility degradation. Finally, treatment cells proteasome inhibitor overrides capacity degrade These demonstrate targeted high