Abstract

E6 oncoproteins from cancer associated Human Papillomaviruses (HPV) associate with a subset of cellular proteins that contain PDZ motifs. Genetic evidence has shown that the interaction of E6 with cellular PDZ proteins is necessary for both full HPV virus replication in human keratinocytes and transformed phenotypes in mouse squamous cells. As several different complexes of cellular proteins interact with E6 via PDZ interactions, the significance of particular PDZ containing targets of E6 is not defined. We have used a proteomics approach to identify complexes of cellular proteins that interact with cancer associated E6 oncoproteins. This has identified novel complexes of cellular proteins that interact with E6 by PDZ ligand interactions. The purpose of this application is to characterize the PDZ complexes we have identified, and to explore the biological significance of E6-PDZ protein interactions.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA120352-04
Application #
7902101
Study Section
Virology - B Study Section (VIRB)
Program Officer
Blair, Donald G
Project Start
2007-09-11
Project End
2012-07-31
Budget Start
2010-08-01
Budget End
2012-07-31
Support Year
4
Fiscal Year
2010
Total Cost
$287,850
Indirect Cost

  Institution

Name
University of Virginia
Department
Pathology
Type
Schools of Medicine
DUNS #
065391526
City
Charlottesville
State
VA
Country
United States
Zip Code
22904

  Publications

Webb Strickland, Sydney; Brimer, Nicole; Lyons, Charles et al. (2018) Human Papillomavirus E6 interaction with cellular PDZ domain proteins modulates YAP nuclear localization. Virology 516:127-138
Brimer, Nicole; Vande Pol, Scott B (2014) Papillomavirus E6 PDZ interactions can be replaced by repression of p53 to promote episomal human papillomavirus genome maintenance. J Virol 88:3027-30
Vande Pol, Scott B; Klingelhutz, Aloysius J (2013) Papillomavirus E6 oncoproteins. Virology 445:115-37
Zanier, Katia; Charbonnier, Sebastian; Sidi, Abdellahi Ould M'hamed Ould et al. (2013) Structural basis for hijacking of cellular LxxLL motifs by papillomavirus E6 oncoproteins. Science 339:694-8
Zou, Wei; Deselm, Carl J; Broekelmann, Thomas J et al. (2012) Paxillin contracts the osteoclast cytoskeleton. J Bone Miner Res 27:2490-500
Ansari, Tina; Brimer, Nicole; Vande Pol, Scott B (2012) Peptide interactions stabilize and restructure human papillomavirus type 16 E6 to interact with p53. J Virol 86:11386-91
Brimer, N; Lyons, C; Wallberg, A E et al. (2012) Cutaneous papillomavirus E6 oncoproteins associate with MAML1 to repress transactivation and NOTCH signaling. Oncogene 31:4639-46
Wade, Ramon; Brimer, Nicole; Lyons, Charles et al. (2011) Paxillin enables attachment-independent tyrosine phosphorylation of focal adhesion kinase and transformation by RAS. J Biol Chem 286:37932-44
Jha, Sudhakar; Vande Pol, Scott; Banerjee, Nilam Sanjib et al. (2010) Destabilization of TIP60 by human papillomavirus E6 results in attenuation of TIP60-dependent transcriptional regulation and apoptotic pathway. Mol Cell 38:700-11
Wade, Ramon; Brimer, Nicole; Vande Pol, Scott (2008) Transformation by bovine papillomavirus type 1 E6 requires paxillin. J Virol 82:5962-6