BINDING OF HIGH-RISK HUMAN-PAPILLOMAVIRUS E6 ONCOPROTEINS TO THE HUMAN HOMOLOG OF THE DROSOPHILA DISCS LARGE TUMOR-SUPPRESSOR PROTEIN

In the majority of cervical cancers, DNAs of high-risk mucosotpropic h uman papillomaviruses (HPVs), such as type 16, are maintained so as to express two viral proteins, E6 and E7, suggesting an essential import ance to carcinogenesis, The high-risk HPV E6 proteins are known to ina ctivate p53 tumor suppressor protein but appear to have an additional, molecularly unknown function(s), In this study, we demonstrate that t hese E6 proteins can bind to the second PDZ domain of the human homolo gue of the Drosophila discs large tumor suppressor protein (hDLG) thro ugh their C-terminal XS/TXV/L (where X represents any amino acid, S/T serine or threonine, and V/L valine or leucine) motif, This finding is similar to the interaction between the adenomatous polyposis coli gen e product and hDLG. E6 mutants losing the ability to bind to hDLG are no longer able to induce E6-dependent transformation of rodent cells, These results suggest an intriguing possibility that interaction betwe en the E6 protein and hDLG or other PDZ domain-containing proteins cou ld be an underlying mechanism in the development of HPV-associated can cers.