Abstract

The genome of SV40 has provided one of the most effective tools in cell and molecular for the analysis of eukaryotic gene expression and oncogenic cell transformation. Depending on the type of cell, the introduction of viral DNA either subverts the host into replicating the viral genome to high copy numbers or alters its properties of growth and tumorigenicity. The mechanisms by which the small genome of SV40 can effect these processes will be studied using a variety of approaches that will involve collaborative interactions between four laboratories. These will include: analysis of the influence of mutant and wild type viral oncogenes on the growth properties of primary and established human cells; utilization of in vitro systems and enzymological approaches to characterize the means by which the viral oncogenes are generated by alternative RNA splicing; charcterization of the interaction of the viral tumor antigens with host cell components; as well as probing the structures of important regions of the viral DNA molecule using a novel set of reagents.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
5P01CA033620-06
Application #
3093519
Study Section
Cancer Special Program Advisory Committee (CAK)
Project Start
1983-06-01
Project End
1992-11-30
Budget Start
1988-12-01
Budget End
1989-11-30
Support Year
6
Fiscal Year
1989
Total Cost
Indirect Cost

  Institution

Name
Columbia University (N.Y.)
Department
Type
Graduate Schools
DUNS #
064931884
City
New York
State
NY
Country
United States
Zip Code
10027

  Publications

Friedman, P N; Chen, X; Bargonetti, J et al. (1993) The p53 protein is an unusually shaped tetramer that binds directly to DNA. Proc Natl Acad Sci U S A 90:3319-23
Bargonetti, J; Manfredi, J J; Chen, X et al. (1993) A proteolytic fragment from the central region of p53 has marked sequence-specific DNA-binding activity when generated from wild-type but not from oncogenic mutant p53 protein. Genes Dev 7:2565-74
Prives, C (1993) Doing the right thing: feedback control and p53. Curr Opin Cell Biol 5:214-8
Harper, J E; Manley, J L (1992) Multiple activities of the human splicing factor ASF. Gene Expr 2:19-29
Friedman, P N; Wang, E H; Meerovitch, K et al. (1992) Murine p53 inhibits the function but not the formation of SV40 T antigen hexamers and stimulates T antigen RNA helicase activity. Chromosoma 102:S60-6
Bargonetti, J; Reynisdottir, I; Friedman, P N et al. (1992) Site-specific binding of wild-type p53 to cellular DNA is inhibited by SV40 T antigen and mutant p53. Genes Dev 6:1886-98
Huber, P W; Morii, T; Mei, H Y et al. (1991) Structural polymorphism in the major groove of a 5S RNA gene complements the zinc finger domains of transcription factor IIIA. Proc Natl Acad Sci U S A 88:10801-5
Bargonetti, J; Friedman, P N; Kern, S E et al. (1991) Wild-type but not mutant p53 immunopurified proteins bind to sequences adjacent to the SV40 origin of replication. Cell 65:1083-91
Fukasawa, K; Sakoulas, G; Pollack, R E et al. (1991) Excess wild-type p53 blocks initiation and maintenance of simian virus 40 transformation. Mol Cell Biol 11:3472-83
Prives, C; Bargonetti, J; Friedman, P N et al. (1991) Functional consequences of the interactions of the p53 tumor suppressor protein and SV40 large tumor antigen. Cold Spring Harb Symp Quant Biol 56:227-35

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