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. 1994 Sep;68(9):5496–5508. doi: 10.1128/jvi.68.9.5496-5508.1994

The kinetics of simian virus 40-induced progression of quiescent cells into S phase depend on four independent functions of large T antigen.

A Dickmanns 1, A Zeitvogel 1, F Simmersbach 1, R Weber 1, A K Arthur 1, S Dehde 1, A G Wildeman 1, E Fanning 1
PMCID: PMC236950  PMID: 8057432

Abstract

Microinjection of purified simian virus 40 large-T-antigen protein or DNA encoding T antigen into serum-starved cells stimulates them to re-enter the cell cycle and progress through G1 into the S phase. Genetic analysis of T antigen indicated that neither its Rb/p107-binding activity nor its p53-binding activity is essential to induce DNA synthesis in CV1P cells. However, T antigens bearing missense mutations that inactivate either activity induced slower progression of the cells into the S phase than did wild-type T antigen. Inactivation of both activities resulted in a T antigen essentially unable to induce DNA synthesis. Missense mutations in either the DNA-binding region of the N terminus also impaired the ability of full-length T antigen to stimulate DNA synthesis in CV1P cells. The wild-type kinetics of cell cycle progression were restored by genetic complementation after coinjection of plasmid DNAs encoding different mutant T antigens or coinjection of purified mutant T-antigen proteins, suggesting that the four mitogenic functions of T antigen are independent. The maximal rate of induction of DNA synthesis in secondary primate cells and established rodent cell lines required the same four functions of T antigen. A model to explain how four independent activities could cooperate to stimulate cell cycle progression is presented.

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Selected References

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