Oncogenic Human Papillomavirus E6 oncoprotein interfere with cell polarity network

FACCIUTO FLORENCIA; BUGNON VALDANO MARINA; MARZIALI, FEDERICO; ANA L. CAVATORTA; LAWRENCE BANKS; GARDIOL DANIELA

Londres

Congreso; Discussion meeting on Cellular Polarity: from mechanisms to disease; 2013

Royal Society

Human Papillomavirus (HPV) E6 oncoproteins have the ability to bind PDZ-domain proteins involved in the organization of cell junctions. Loss of cell polarity is a hallmark for carcinoma development and the regulation of cell polarity depends, in part, of the integrity of cell tight junctions (TJ). For investigating the interference of HPV E6 proteins with TJ structures we analyzed in HPV E6-expressing cells the level and distribution of components of the Par polarity complex, a key element in this kind of junction. We showed by inmmunofluorescence assays that the expression of high risk HPV E6 results in a dramatic change in Par3 cell distribution in a PDZ dependent manner. We observed that E6 oncoproteins and Par3 interact in vivo and this protein binding does not result in a significant reduction of Par3 protein levels. Moreover, HPV E6 induces a misdistribution of PIP2 (phosphoinositosides), a lipid component of the polarity machinery, as well as interferes with tight junctions? formation in calcium switch assays. In summary, the data suggest that oncogenic HPV have the ability to interfere with key elements of the UT with possible implications for the maintenance of cell polarity.