Scott Vande Pol, M.D., Ph.D.
1985: M.D., University of California, San Diego
1985: Ph.D., University of California, San Diego
1985-1989: Resident in Pathology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892
1989-1993: Postdoctoral Fellow, Laboratory of Tumor Virus Biology, National Cancer Institutes, Bethesda, MD 20892
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.
Brimer N, Vande Pol SB: Papillomavirus E6 PDZ interactions can be replaced by repression of p53 to promote episomal human papillomavirus genome maintenance. J Virol 2014, 88:3027-3030.http://www.ncbi.nlm.nih.gov/pubmed/24352452. DOI: 10.1128/JVI.02360-13.
Brimer N, Wade R, Vande Pol S: Interactions between E6, FAK, and GIT1 at paxillin LD4 are necessary for transformation by bovine papillomavirus 1 E6. J Virol 2014, 88:9927-9933.http://www.ncbi.nlm.nih.gov/pubmed/24942580. DOI: 10.1128/JVI.00552-14.
Vande Pol SB, Klingelhutz AJ: Papillomavirus E6 oncoproteins. Virology 2013, 445:115-137.http://www.ncbi.nlm.nih.gov/pubmed/23711382. DOI: 10.1016/j.virol.2013.04.026.
- Brimer N, Lyons C, Wallberg AE, Vande Pol SB: Cutaneous papillomavirus E6 oncoproteins associate with MAML1 to repress transactivation and NOTCH signaling. Oncogene 2012, 31:4639-4646.http://www.ncbi.nlm.nih.gov/pubmed/22249263. DOI: 10.1038/onc.2011.589.
- Ansari T, Brimer N, Vande Pol SB: Peptide interactions stabilize and restructure human papillomavirus type 16 E6 to interact with p53. J Virol 2012, 86:11386-11391. http://www.ncbi.nlm.nih.gov/pubmed/22896608. DOI: 10.1128/JVI.01236-12.
- Wade R, Brimer N, Lyons C, Vande Pol S: Paxillin enables attachment-independent tyrosine phosphorylation of focal adhesion kinase and transformation by RAS. J Biol Chem 2011, 286:37932-37944.http://www.ncbi.nlm.nih.gov/pubmed/21900245. DOI: 10.1074/jbc.M111.294504.
- Jha S, Vande Pol S, Banerjee NS, Dutta AB, Chow LT, Dutta A: Destabilization of TIP60 by human papillomavirus E6 results in attenuation of TIP60-dependent transcriptional regulation and apoptotic pathway. Mol Cell 2010, 38:700-711. http://www.ncbi.nlm.nih.gov/pubmed/20542002. DOI: 10.1016/j.molcel.2010.05.020.
- Wade R, Brimer N, Vande Pol S: Transformation by bovine papillomavirus type 1 E6 requires paxillin. J Virol 2008, 82:5962-5966. http://www.ncbi.nlm.nih.gov/pubmed/18385245. DOI: 10.1128/JVI.02747-07.
- Jing M, Bohl J, Brimer N, Kinter M, Vande Pol SB: Degradation of tyrosine phosphatase PTPN3 (PTPH1) by association with oncogenic human papillomavirus E6 proteins. J Virol 2007, 81:2231-2239.http://www.ncbi.nlm.nih.gov/pubmed/17166906. DOI: 10.1128/JVI.01979-06.
- Wade R, Vande Pol S: Minimal features of paxillin that are required for the tyrosine phosphorylation of focal adhesion kinase. Biochem J 2006, 393:565-573. http://www.ncbi.nlm.nih.gov/pubmed/16253116. DOI: 10.1042/BJ20051241.
- Cooper B, Brimer N, Stoler M, Vande Pol SB: Suprabasal overexpression of beta-1 integrin is induced by bovine papillomavirus type 1. Virology 2006, 355:102-114. http://www.ncbi.nlm.nih.gov/pubmed/16899269. DOI: 10.1016/j.virol.2006.06.032.