Abstract

Papillomaviruses are causative agents in the most prevalent lethal cancer in women world-wide: cervical cancer. As such, the mechanisms by which their oncoproteins transform cells is biologically interesting and medically significant. One important function of the cancer associated papillomaviruses is the targeted degradation of the p53 tumor suppressor, which is mediated by the association of the E6 oncoprotein with the cellular ubiquitin ligase E6AP. In this proposal we will determine the structural features of 16E6, E6AP, and p53 that determine the capacity of each of these proteins to form a complex. We will then utilize the mutants derived in this study to determine the biological relevance of cellular proteins that interact with E6, and elucidate the molecular features required for the degradation of the p53 tumor suppressor.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA080931-03
Application #
6497535
Study Section
Virology Study Section (VR)
Program Officer
Wong, May
Project Start
2000-02-01
Project End
2005-01-31
Budget Start
2002-03-08
Budget End
2003-01-31
Support Year
3
Fiscal Year
2002
Total Cost
$352,976
Indirect Cost

  Institution

Name
Case Western Reserve University
Department
Pathology
Type
Schools of Medicine
DUNS #
077758407
City
Cleveland
State
OH
Country
United States
Zip Code
44106

  Publications

Sidi, Abdellahi Ould M'hamed Ould; Babah, Khaled Ould; Brimer, Nicole et al. (2011) Strategies for bacterial expression of protein-peptide complexes: application to solubilization of papillomavirus E6. Protein Expr Purif 80:8-16
Cooper, Brooke; Brimer, Nicole; Vande Pol, Scott B (2007) Human papillomavirus E6 regulates the cytoskeleton dynamics of keratinocytes through targeted degradation of p53. J Virol 81:12675-9
Bohl, Joanna; Brimer, Nicole; Lyons, Charles et al. (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 282:9392-400
Jing, Ming; Bohl, Joanna; Brimer, Nicole et al. (2007) Degradation of tyrosine phosphatase PTPN3 (PTPH1) by association with oncogenic human papillomavirus E6 proteins. J Virol 81:2231-9
Brimer, Nicole; Lyons, Charles; Vande Pol, Scott B (2007) Association of E6AP (UBE3A) with human papillomavirus type 11 E6 protein. Virology 358:303-10
Wade, Ramon; Vande Pol, Scott (2006) Minimal features of paxillin that are required for the tyrosine phosphorylation of focal adhesion kinase. Biochem J 393:565-73
Cooper, Brooke; Brimer, Nicole; Stoler, Mark et al. (2006) Suprabasal overexpression of beta-1 integrin is induced by bovine papillomavirus type 1. Virology 355:102-14
Cooper, Brooke; Schneider, Steven; Bohl, Joanna et al. (2003) Requirement of E6AP and the features of human papillomavirus E6 necessary to support degradation of p53. Virology 306:87-99