Papillomaviruses are small DNA viruses that can cause cancer in their natural hosts. Up to 95% of cervical cancers, the second leading malignancy of women worldwide, containing the """"""""high risk"""""""" type of the virus. The bovine papillomavirus (BPV) has been a useful model for studying the molecular pathways of the viral life cycle. The BPV oncoprotein, E6, binds paxillin, a focal adhesion, LIM domain containing regulatory protein that has been proposed to be associated with proliferative signals. The BPV E6- paxillin interaction strongly correlates with transformation. BPV E6 may also interact with hic5, another LIM domain protein that has a high degree of structural homology to paxillin and may be involved in negative growth regulation. The cancer associated human PV (HPV) 16E6 binds to paxillin in vitro, although the relevance of this interaction to oncogenesis is unclear. It is unknown if HPV 16E6 bindings to paxillin in vitro, although the relevance of this interaction to the functional consequences of the interactions between the BPV and HPV oncoprotein E6 and paxillin and hic5 in order to better understand papillomavirus transformation mechanisms. I will determine whether hic5 is a possible target for BPV 36 and HPV 16E6 in transformation, determine the effects of paxillin and hic5 over-expression in the presence and absence of BPV and HPV E6, and identify cellular proteins that are competed from paxillin and hic5 by BPV and HPV E6. These studies will enhance our understanding of how papillomaviruses cause cancer and provide additional insights into cellular growth control and how its deregulation leads to the development of neoplasia.
