The proposed studies are continuations of investigations into the biological properties of SV40 early proteins. During the previous project period, we demonstrated the antigenic relatedness of the known SV40 early proteins to large T-antigen, detected the presence of large T-polypeptide in the plasma membrane of SV40-infectd and -transformed cells, demonstrated antigenic differences betweem T-polypeptides in nuclei and plasma membranes, showed that a cytoplasmic form of SV40 T-antigen induced by an SV40-adenovirus 7 hybrid virus inhibited the nuclear migration of wild-type T-antigen, and delineated a difference in phosphorylation between nuclear and cytoplasmic forms of T-antigen. It proposed to further characterize the membrane-associated T-antigen and to define the regions of the T-polypeptide which confer various functional activities to the molecule and which govern its movement to specific intracellular compartments. The role of the membrane-bound T-antigen in TSTA activity will be defined, as will its ability to interact with cellular proteins, such as non-viral T-antigen and major histocompatibility complex products. Attempts will be made to transfer the mutated gene which codes for cytoplasmic T-antigen from the hybrid virus back to SV40. These studies will expand our understanding of the biological functions of virus-induced early proteins in transformed cells and will provide important insights into the process of neoplastic transformation in general.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA022555-08
Application #
3165848
Study Section
Virology Study Section (VR)
Project Start
1978-01-01
Project End
1985-12-31
Budget Start
1985-01-01
Budget End
1985-12-31
Support Year
8
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Baylor College of Medicine
Department
Type
Schools of Medicine
DUNS #
074615394
City
Houston
State
TX
Country
United States
Zip Code
77030
Lednicky, J A; Jafar, S; Wong, C et al. (1997) High-fidelity PCR amplification of infectious copies of the complete simian virus 40 genome from plasmids and virus-infected cell lysates. Gene 184:189-95
Lednicky, J A; Butel, J S (1997) Tissue culture adaptation of natural isolates of simian virus 40: changes occur in viral regulatory region but not in carboxy-terminal domain of large T-antigen. J Gen Virol 78 ( Pt 7):1697-705
Lednicky, J A; Butel, J S (1997) A coupled PCR and restriction digest method for the detection and analysis of the SV40 regulatory region in infected-cell lysates and clinical samples. J Virol Methods 64:1-9
Lednicky, J A; Stewart, A R; Jenkins 3rd, J J et al. (1997) SV40 DNA in human osteosarcomas shows sequence variation among T-antigen genes. Int J Cancer 72:791-800
Stewart, A R; Lednicky, J A; Benzick, U S et al. (1996) Identification of a variable region at the carboxy terminus of SV40 large T-antigen. Virology 221:355-61
Lednicky, J A; Garcea, R L; Bergsagel, D J et al. (1995) Natural simian virus 40 strains are present in human choroid plexus and ependymoma tumors. Virology 212:710-7
Lednicky, J A; Wong, C; Butel, J S (1995) Artificial modification of the viral regulatory region improves tissue culture growth of SV40 strain 776. Virus Res 35:143-53
Sawai, E T; Rasmussen, G; Butel, J S (1994) Construction of SV40 deletion mutants and delimitation of the binding domain for heat shock protein to the amino terminus of large T-antigen. Virus Res 31:367-78
Fromm, L; Shawlot, W; Gunning, K et al. (1994) The retinoblastoma protein-binding region of simian virus 40 large T antigen alters cell cycle regulation in lenses of transgenic mice. Mol Cell Biol 14:6743-54
Sawai, E T; Butel, J S (1992) Epitope mapping and conformational analysis of SV40 T-antigen deletion mutants. Virology 189:782-5

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