Scott Vande Pol, M.D., Ph.D.
Scott Vande Pol, M.D.,
Associate Professor of
||M.D., University of California, San
||Ph.D., University of California, San
||Resident in Pathology, National Cancer
Institute, National Institutes of Health, Bethesda, MD 20892
||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
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.
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,
Vande Pol SB, Klingelhutz AJ:
Papillomavirus E6 oncoproteins. Virology 2013,
- 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.
- 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.
- 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,
- 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.
- Wade R, Brimer N, Vande Pol S: Transformation by
bovine papillomavirus type 1 E6 requires paxillin. J Virol 2008,
- 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.
- 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.
- 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.