E6 proteins HPV oncogenic types delocalizes PIP2 lipids that regulates polarity

FACCIUTO FLORENCIA; BUGNON VALDANO MARINA; ANA L. CAVATORTA; DANIELA GARDIOL

Puerto Madryn

Congreso; XLVI Reunión Anual de la Sociedad Argentina de Investigación en Bioquímica y Biología Molecular (SAIB).; 2010

SAIB

Human Papillomavirus (HPV) E6 oncoproteins binds  PDZ-domain proteins involved in  cell junction organization. For investigating the interference of HPV E6 protein with tight junction structures, important for the maintenence of cell polarity we are analizing  the level and distribution of tight junction proteins in E6-positive cells. We observed , by Inmunofluorescense assays, that Par-3 protein, a key element of this kind of junctions, localizes at cell cell interaction in epithelial cells, and high risk HPV E6 protein appears to alter Par 3 cell localization. Cell polarity also implies the correct distribution of membrane Phosphoinositide (PIP) lipids. It has been demostrated that some PDZ proteins interact with these lipids  and this interaction  is relevant for PIP correct distribution. We want to address if E6 HPV proteins could disrupt the interaction PIPs –PDZ, interfering with PIPs localization and tight junction complexes. For this purpose we analized the differences in PIP distribution in presence and absence of E6proteins using PIP biosensor fused to GFP. Preliminary results have shown that E6 expression induces PIP mislocalization, reducing their presence at cell borders. Moreover, cancer HPV positive cells showed a completely altered pattern of PIP localization with a punctuated cytoplasmic distribution.