PAR3 polarity protein, a target of HPV E6, is also mislocalized by HTLV-1 Tax oncoprotein

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

Workshop; First ICGEB Workshop "Human Papillomavirus:From Basic Biology to Cervical Cancer Prevention?; 2014

Viral oncoproteins from different oncovirus, like Human Papillomavirus (HPV) E6 and Human T -cell Leukemia Virus type I (HTLV -1) Tax, have the ability to bind and interfere with PDZ proteins that form the conserved Scribble, Par and Crumbs polarity complexes. The different viral oncoproteins target the same pool of polarity proteins and these interactions seem to be important in the progression towards malignancy during infection. We recently demonstrated that E6 proteins from high risk HPVs interfere with the normal distribution of the PDZ protein PAR3, a key regulator of cell polarity and an integrator of different signaling cascades that regulate cell proliferation. We wanted to address if similarly to other PDZ polarity proteins, PAR3 was also a common target for HTLV -1 Tax protein. By inmunofluorescense assays in epithelial cells we showed that the expression of Tax-1 clearly alters the subcellular localization of PAR3 from the cell contacts to the cytoplasm. However, by co-inmunoprecipitation experiments we could not demonstrate the interaction between Tax-1 and PAR3 proteins. Considering the well-established intercommunication between members of the polarity complexes it is possible that the binding of Tax-1 to other PDZ proteins previously identified, as Disc Large 1 (DLG1) or hScrib, could be responsible for the observed PAR3 misdistribution. Hence we initiated studies to analyze how changes in the expression of a particular PDZ polarity protein, normally targeted by E6 or Tax-1, impacts on the expression of PAR3. In this sense, HaCaT epithelial cells were separately silenced for hScrib, DLG1 or PAR3 expression and in each case the localization and expression levels of the remaining proteins were ascertained by immunofluoresce. Results showed that PAR3 expression at the cell borders was strongly reduced in cells ablated for hScrib or DLG1 expression; on the contrary, no significant changes for hScrib or DLG1 were observed in the absence of PAR3 protein. These results, although preliminary, suggest that PAR3 normal localization and levels are highly dependent on hScrib and DLG1 correct expression