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PMID: 1658380 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

The ability of simian virus 40 large T antigen to immortalize primary mouse embryo fibroblasts cosegregates with its ability to bind to p53.

Journal of virology ·Vol. 65 ·No. 12 ·1991-12-00 ·Pages 6872-80

Zhu JY, Abate M, Rice PW, Cole CN

Abstract

The large T antigen encoded by simian virus 40 (SV40) plays essential roles in the infection of permissive cells, leading to production of progeny virions, and in the infection of nonpermissive cells, leading to malignant transformation. Primary mouse embryo fibroblasts (MEFs) are nonpermissive for SV40, and infection by wild-type SV40 leads to immortalization and transformation of a small percentage of infected cells. We examined the ability of an extensive set of mutants whose lesions affect SV40 large T antigen to immortalize MEFs. We found that immortalization activity was retained by all mutants whose lesions are located upstream of codon 346. This includes a mutant lacking amino acids 168 to 346. We previously showed (M. J. Tevethia, J. M. Pipas, T. Kierstead, and C. Cole, Virology 162:76-89, 1988) that sequences downstream of amino acid 626 are not required for immortalization of primary MEFs. Studies by Thompson et al. (D. L. Thompson, D. Kalderon, A. Smith, and M. Tevethia, Virology 178:15-34, 1990) indicate that all sequences upstream of residue 250, including the domain for binding of tumor suppressor protein Rb, are not required for transformation of MEFs. Together, these studies demonstrate that the immortalization activity of large T antigen for MEFs maps to sequences between 347 and 626. Several mutants with lesions between 347 and 626 retained the ability to immortalize at nearly the wild-type frequency, while others, with small insertions at amino acid 409 or 424 or a deletion of residues 587 to 589, failed to immortalize. The abilities of mutant T antigens to form a complex with tumor suppressor protein p53 were examined. We found that all mutants able to immortalize retained the ability to complex with p53, while all mutants which lost the ability to immortalize were no longer able to bind p53. This suggests that inactivation of the growth-suppressive properties of p53 is essential for immortalization of MEFs.

Related Genes
dlA
MeSH Terms
Animals Antigens, Polyomavirus Transforming/genetics,physiology Base Sequence Cell Line Cell Line, Transformed Cell Transformation, Neoplastic Mice Molecular Sequence Data Mutagenesis, Insertional Oligodeoxyribonucleotides Protein Binding Simian virus 40/genetics,immunology Transcriptional Activation Tumor Suppressor Protein p53/metabolism
Chemicals
Antigens, Polyomavirus Transforming Oligodeoxyribonucleotides Tumor Suppressor Protein p53
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Zhu J Y
Department of Biochemistry, Dartmouth Medical School, Hanover, New Hampshire 03755-3844.
Abate M
Rice P W
Cole C N
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Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
0022-538X
DOI
10.1128/JVI.65.12.6872-6880.1991
Published
1991-12-00
Pages
6872-80
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC250785
Subset
IM
Grants
NCI NIH HHS · CA08835 · United States
NCI NIH HHS · CA23018 · United States
NCI NIH HHS · CA39259 · United States
External Links
PubMed source DOI: 10.1128/JVI.65.12.6872-6880.1991 PMC Full Text View journal details
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