Human and Primate Tumour viruses use PDZ binding as an evolutionarily conserved mechanism of targeting cell polarity regulators

VJEKOSLAV TOMAIC, DANIELA GARDIOL, PAOLA MASSIMI, MICHELLE OZBUN, MICHAEL MYERS, LAWRENCE BANKS

University of Wisconsin, Madison. Estados Unidos

Congreso; The 2008 Molecular Biology of DNA Tumor Viruses Conference; 2008

A unique feature of the cancer-causing mucosotropic Human Papillomaviruses is the ability of their E6 proteins to interact with a number of PDZ domain-containing cellular substrates, including the cell polarity regulators hDlg and hScrib. These interactions are essential for the ability of these viruses to induce malignant progression. Rhesus Papillomaviruses are similar to their human counterparts in that they also cause anogenital malignancy in their host, the Rhesus Macaque. However, unlike HPV E6, the RhPV E6 has no PDZ binding motif. We now show that such a motif is present on the RhPV E7 oncoprotein. This motif specifically confers PDZbinding activity and directs the interaction of RhPV E7 with the cell polarity regulator Par3, which it targets for proteasome mediated degradation. These results demonstrate an amazing evolutionary conservation of function between the RhPV and the HPV oncoproteins, where both target proteins of the same cell polarity control network, albeit through different components and pathways.