High Risk HPVs interfere with the regulation of the Par polarity complex

FACCIUTO, FLORENCIA; MARZIALI, FEDERICO; MASSIMI, PAOLA; BUGNON VALDANO MARINA; CAVATORTA, ANA LAURA; BANKS, LAWRENCE; GARDIOL, DANIELA

Trieste

Congreso; ICGEB DNA Tumour Virus Meeting 2015; 2015

ICGEB

Epithelial cells establish and maintain the apical-basal polarity through the coordinated functions of three protein polarity complexes called the Scrib, Par and Crumbs complexes. Oncogenic viruses, such as high risk Human Papillomavirus (HPV), have been shown to encode proteins that disrupt cell polarity, an important event in the progression towards malignancy during infection. The Par complex, formed by the scaffold Partitioning defective 3 (PAR3) and Partitioning defective 6 (PAR6) proteins and the atypical protein kinase C (aPKC), is crucial for the tight junction formation and signal transduction processes. Recently, we reported evidences of alterations in the expression of PAR3 stimulated by high risk HPVs. Immunofluorescence and immunoprecipitation experiments have shown the loss of PAR3 normal expression from the cell borders, together with redistribution to the cytoplasm and nucleus, in the presence of the HPV E6 oncoprotein. To fully explore the mechanisms involved behind this observation, we considered the potential cross-talk events among the different polarity complexes. This could be relevant considering that members of other complexes, like Disc Large 1 (DLG1) and hScrib proteins are well-characterized partners of E6. Hence, we initiated studies to analyze how changes in the expression of a particular polarity protein, normally targeted by E6, impacts on the expression of PAR3.