Abstract

Our work in this project is concerned with identifying discrete functions of the polyoma virus middle and small tumor antigens as they relate to virus replication and transformation of cells in culture, and to replication and induction Of tumors in the mouse. The first group of Aims focuses on the middle T antigen as the major transforming protein, its role in binding phospholipase C, the possible importance of its serving as a substrate for a cyclin dependent protein kinase, and the possible role of a proline-rich segment of the protein in transducing signals via SH3 or other cellular proteins. The second group of Aims focuses on the small T protein and particularly on the behavior of a virus mutant blocked in expression of this protein. The role of specific sequences involved in binding the phosphatase PP2A, or the DNA-J domain, will be studied. This project relates to the larger framework of the Program Project Grant which brings together an interactive group of investigators all concerned with studying oncoprotein functions of DNA-containing tumor viruses.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
5P01CA050661-14
Application #
6575615
Study Section
Project Start
2002-03-01
Project End
2003-02-28
Budget Start
Budget End
Support Year
14
Fiscal Year
2002
Total Cost
$228,401
Indirect Cost

  Institution

Name
Dana-Farber Cancer Institute
Department
Type
DUNS #
149617367
City
Boston
State
MA
Country
United States
Zip Code
02215

  Publications

Becker, Jürgen C; Stang, Andreas; Hausen, Axel Zur et al. (2018) Epidemiology, biology and therapy of Merkel cell carcinoma: conclusions from the EU project IMMOMEC. Cancer Immunol Immunother 67:341-351
Becker, Jürgen C; Stang, Andreas; DeCaprio, James A et al. (2017) Merkel cell carcinoma. Nat Rev Dis Primers 3:17077
Denis, Deborah; Rouleau, Cecile; Schaffhausen, Brian S (2017) A Transformation-Defective Polyomavirus Middle T Antigen with a Novel Defect in PI3 Kinase Signaling. J Virol 91:
Starrett, Gabriel J; Marcelus, Christina; Cantalupo, Paul G et al. (2017) Merkel Cell Polyomavirus Exhibits Dominant Control of the Tumor Genome and Transcriptome in Virus-Associated Merkel Cell Carcinoma. MBio 8:
Cizmecioglu, Onur; Ni, Jing; Xie, Shaozhen et al. (2016) Rac1-mediated membrane raft localization of PI3K/p110? is required for its activation by GPCRs or PTEN loss. Elife 5:
Rouleau, Cecile; Pores Fernando, Arun T; Hwang, Justin H et al. (2016) Transformation by Polyomavirus Middle T Antigen Involves a Unique Bimodal Interaction with the Hippo Effector YAP. J Virol 90:7032-7045
Luo, Leo Y; Kim, Eejung; Cheung, Hiu Wing et al. (2015) The Tyrosine Kinase Adaptor Protein FRS2 Is Oncogenic and Amplified in High-Grade Serous Ovarian Cancer. Mol Cancer Res 13:502-9
Hettmer, Simone; Schinzel, Anna C; Tchessalova, Daria et al. (2015) Functional genomic screening reveals asparagine dependence as a metabolic vulnerability in sarcoma. Elife 4:
White, Elizabeth A; Kramer, Rebecca E; Hwang, Justin H et al. (2015) Papillomavirus E7 oncoproteins share functions with polyomavirus small T antigens. J Virol 89:2857-65
Spurgeon, Megan E; Cheng, Jingwei; Bronson, Roderick T et al. (2015) Tumorigenic activity of merkel cell polyomavirus T antigens expressed in the stratified epithelium of mice. Cancer Res 75:1068-79

Showing the most recent 10 out of 147 publications