The overall objective is to identify domains of the large T antigen of SV40 that modulate the transformation of cells in culture and tumorigenicity. More specifically, we will identify those portions of this dominant viral oncogene product that confer individual characteristics of the transformed cell phenotype and those that are dispensible to the processes. We have already shown that at least some of the transformed cell properties are separable genetically. By localizing immortalizing capacity, ability to form dense foci, ability to form colonies in semisolid medium and tumorigenicity to distinct portions of T antigen it should be possible to predict those functions of the protein that cooperate in fully transforming specific rodent cells in culture and in producing tumors. Particular interest will placed on the role of T antigen in the plasma membrane in the processes of transformation and tumorigenesis. Both detection and immune-selection methods for the isolation and analysis of mutants that produce T antigens that have lost the ability to associate normally with the surface of cells are proposed. In addition, the association between functions marked by the hr-t mutant in polyoma virus and a mutant of SV40 with a similar phenotype will be probed. Finally, three specific regions of the T antigen coding sequence, a possible immortalizing domain, a region possibly associated with aberrent expression of surface T antigen, and the nucleotides surrounding the lesion in the hr-t-like mutant of SV40, will be mutagenized exhaustively in order to expand representation of these areas by mutants whose characterization will assess the impact of specific functions on lytic growth and transformation by SV40.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA024694-12
Application #
3166550
Study Section
Experimental Virology Study Section (EVR)
Project Start
1978-09-01
Project End
1991-08-31
Budget Start
1989-09-01
Budget End
1990-08-31
Support Year
12
Fiscal Year
1989
Total Cost
Indirect Cost
Name
Pennsylvania State University
Department
Type
Schools of Medicine
DUNS #
129348186
City
Hershey
State
PA
Country
United States
Zip Code
17033