The long-range goal of our research is to understand the process by which simian virus 40 acts to transform cells in culture and to cause tumors in animals. We propose to examine the roles that SV40-encoded proteins play in transformation and oncogenicity. By understanding the mechanism of SV40 oncogenesis, we hope to move closer to an understanding of human cancer.
Our specific aims are to use an SV40 early region deletion mutant that we have isolated to discover the SV40 functions that are involved in cellular transformation and oncogenesis. The mutant, F8dl, lacks over 60% of the coding sequences for the SV40 large tumor antigen and yet this mutant still can transform and cause tumors. We propose to answer the following questions: 1) Does the F8dl-encoded T antigen bind to specific sites on cellular DNA? 2) Does the F8dl-encoded T antigen bind to specific sequences on cellular chromatin? 3) Are interactions of T antigen within cellular nuclei important for transformation and if so, how does T antigen act within the nucleus to transform?

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA034072-05
Application #
3171812
Study Section
Experimental Virology Study Section (EVR)
Project Start
1983-04-01
Project End
1989-11-30
Budget Start
1987-12-01
Budget End
1988-11-30
Support Year
5
Fiscal Year
1988
Total Cost
Indirect Cost
Name
University of Colorado at Boulder
Department
Type
Schools of Arts and Sciences
DUNS #
City
Boulder
State
CO
Country
United States
Zip Code
80309
Sompayrac, L; Danna, K J (1994) An amino-terminal fragment of SV40 T antigen induces cellular DNA synthesis in quiescent rat cells. Virology 200:849-53
Sompayrac, L; Danna, K J (1992) An amino-terminal fragment of SV40 T antigen transforms REF52 cells. Virology 191:439-42
Sompayrac, L; Danna, K J (1991) The amino-terminal 147 amino acids of SV40 large T antigen transform secondary rat embryo fibroblasts. Virology 181:412-5
Sompayrac, L; Danna, K J (1990) Method to identify genomic targets of DNA binding proteins. Proc Natl Acad Sci U S A 87:3274-8
Sompayrac, L; Danna, K J (1989) An SV40 mutant oncoprotein has a nuclear location. Virology 171:267-70
Sompayrac, L; Danna, K J (1988) A new SV40 mutant that encodes a small fragment of T antigen transforms established rat and mouse cells. Virology 163:391-6
Sompayrac, L; Danna, K J (1986) An SV40 mutant T antigen does not bind the SV40 viral origin. Virology 153:297-309
Sompayrac, L; Danna, K J (1985) The SV40 T-antigen gene can have two introns. Virology 142:432-6
Pan, S; Sompayrac, L M; Knowles, B B et al. (1985) A fragment of the simian virus 40 early genome can induce tumors in nude mice. J Virol 53:988-9
Sompayrac, L; Danna, K J (1985) The simian virus 40 sequences between 0.169 and 0.423 map units are not essential to immortalize early-passage rat embryo cells. Mol Cell Biol 5:1191-4