Our studies of the BPV-1 E6 oncoprotein found that it associated with a cellular regulatory adapter molecule called paxillin.  We showed that paxillin was required for the tyrosine phosphorylation of Focal Adhesion Kinase, a central regulator of integrin signaling, cell attachment and migration.  We now have evidence that paxillin is required for the activity of many cancer-associated oncoproteins. We are elucidating the role of paxillin in cancer signal transduction and survival.
 
A second project has been devoted to understanding of the mechanism by which E6 oncoproteins activate the ubiquitin mediated degradation of tumor supressor proteins, such as p53. We are engaged in a collaboration to solve the solution structure of the E6.   In the process of these studies, we identified interaction motifs on E6 that allow for the interaction of E6 with tumor supressors.    We have recently identified a new cellular protein that is targeted for degradation by E6 together with a cellular ubiquitin ligase.  This new target is a tyrosine phosphatase about which little is known.  We suspect that by targeting this phosphatase for degradation, that E6 manipulates cellular signaling to facilitate the viral life cycle.  Given that human HPV containing tumors all express E6, this phosphatase may prove to be an important target in the development of cancers, both viral positive and negative.   

• Wade, R., and S. Vande Pol. 2006. Minimal features of paxillin that are required for the tyrosine phosphorylation of focal adhesion kinase. Biochem J 393:565-73.

• Cooper, B., Brimer, N., Stoler, M., and Vande Pol, S.B.  2006.  Suprabasal Overexpression of Beta-1 Integrin is induced by Bovine Papillomavirus Type 1.  Virology . 2006 Nov 10;355(1):102-14. Epub 2006 Aug 8. PMID: 16899269.

• Brimer, N., Lyons, C., and Vande Pol, S.B.  2006.  Association of E6AP (UBE3A) with Human Papillomavirus Type 11 E6 Protein. Virology.  2007 Feb 20;358(2):303-10. Epub 2006 Oct 4.   PMID: 17023019

• Jing, M.,  Bohl, J., Brimer, N.,   Kinter, M., and Vande Pol, S.B.  2006.  Degradation of Tyrosine Phosphatase PTPN3 (PTPH1) by association with Oncogenic Human Papillomavirus E6 Proteins   J Virol. 2007 Mar;81(5):2231-9. Epub 2006 Dec 13.  PMID: 17166906

• Bohl, J.,  Brimer, N., Lyons, C., and Vande Pol, S.B. 2007.  The stardust family protein MPP7 forms a tripartite complex with LIN7 and DLG1 that regulates the stability and localization of DLG1 to cell junctions. J Biol Chem. 2007 Mar 30;282(13):9392-400. Epub 2007 Jan 19.   PMID: 17237226

• Cooper, B., Brimer, N., and Vande Pol, S.B. Human Papillomavirus E6 Regulates the Cytoskeleton Dynamics of Keratinocytes Through Targeted Degradation of p53. J Virol. 2007 Nov;81(22):12675-9. Epub 2007 Sep 5.  PMID: 17804489

• Wade, R., Brimer, N., and Vande Pol, S.B. Transformation by Bovine Papillomavirus Type 1 E6 Requires Paxillin.  J. Virol. 2008 Jun;82(12):5962-6. Epub 2008 Apr 2.PMID: 18385245.