This project examines two aspects of the polyoma tumor antigens: (1) how structure is related to function within each protein and, (2) how the T antigens interact with cellular components to exert their regulatory effect on the cell. Recombinant DNA techniques are used to overproduce the T antigens and the individual proteins are purified from the resulting strains. Purified proteins can then tested for biological or biochemical function. Subsequently they can be used as reagents for raising banks of monoclonal antibodies for structural studies and as affinity reagents for studying interactios with host cell proteins. To complement these biochemical approaches, genetic studies will be done using retrovirus vectors which transduce the individual T antigens. A library of missense mutants of middle T antigens which have conditionally or absolutely lost transforming function will be made using the virus vectors. Interesting mutations will be characterized biochemically and sequenced at the DNA level to yield structure function data for the proteins. Together, the biochemical and genetic approaches will eventually allow us to overproduce mutant T-antigens so that they can be purified for further study. Such a situation should yield valuable information about the manner in which polyoma T antigens alter a cell to a transformed state.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
2R01CA030002-04
Application #
3168960
Study Section
Experimental Virology Study Section (EVR)
Project Start
1982-02-01
Project End
1988-01-31
Budget Start
1985-02-01
Budget End
1986-01-31
Support Year
4
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Dana-Farber Cancer Institute
Department
Type
DUNS #
149617367
City
Boston
State
MA
Country
United States
Zip Code
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
Hashim, D; Sartori, S; Brennan, P et al. (2016) The role of oral hygiene in head and neck cancer: results from International Head and Neck Cancer Epidemiology (INHANCE) consortium. Ann Oncol 27:1619-25
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Hwang, Justin H; Pores Fernando, Arun T; Faure, Nathalie et al. (2014) Polyomavirus small T antigen interacts with yes-associated protein to regulate cell survival and differentiation. J Virol 88:12055-64
Schmit, Fabienne; Utermark, Tamara; Zhang, Sen et al. (2014) PI3K isoform dependence of PTEN-deficient tumors can be altered by the genetic context. Proc Natl Acad Sci U S A 111:6395-400
Jia, Shidong; Gao, Xueliang; Lee, Sang Hyun et al. (2013) Opposing effects of androgen deprivation and targeted therapy on prostate cancer prevention. Cancer Discov 3:44-51
Utermark, Tamara; Rao, Trisha; Cheng, Hailing et al. (2012) The p110ýý and p110ýý isoforms of PI3K play divergent roles in mammary gland development and tumorigenesis. Genes Dev 26:1573-86
Ni, Jing; Liu, Qingsong; Xie, Shaozhen et al. (2012) Functional characterization of an isoform-selective inhibitor of PI3K-p110? as a potential anticancer agent. Cancer Discov 2:425-33

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