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Dissection of the T Antigen/Mouse p53 Complex and Its Inhibitory Effects on Viral Origin-Directed DNA Replication in Vivo and in Vitro

  • H.-W. Stürzbecher
  • K. Rudge
  • R. Brain
  • C. Addison
  • M. Grimaldi
  • J. R. Jenkins
Part of the Current Topics in Microbiology and Immunology book series (CT MICROBIOLOGY, volume 144)

Abstract

Several lines of evidence suggest that the cellular phosphoprotein p53, overproduced in a variety of neoplastic cell types (reviewed in Crawford 1983; Jenkins and Stürzbecher 1988; Oren 1985; Rotter and Wolf 1985), is an oncogene product, directly involved in the process of malignant transformation. p53 cDNA expression constructs immortalise both adult (Jenkins et al. 1984, 1985) and embryo (Jenkins et al. 1985; Rovinski and Benchimol 1988) cells and cooperate with an activated ras oncogene in malignant transformation (Eliyahu et al. 1984; Jenkins et al. 1984; Parada et al. 1984; Rovinski and Benchimol 1988; Finlay et al. 1988). The potential of wild-type p53 to score in transformation assays is dependent upon powerful heterologous promoter/enhancers driving p53 expression (Jenkins et al. 1984, 1985). Immortalisation and ras complementation are distinct activities of p53 and can be separated by deletion mutagenesis (Jenkins et al. 1985). Generation of specific variant p53 species can give rise to protein products with increased stability and enhanced transforming/biological activity (Jenkins et al. 1985), indicating that the p53 gene can be mutationally activated. Near identical arrangements of the endogenous p53 gene coding sequences have been identified in vivo and are associated with malignant transformation by Friend leukaemia virus (Rovinski et al. 1987). Subsequently, further in vitro-generated p53 mutants with enhanced activity in cotransformation assays have been identified (Finlay et al. 1988).

Keywords

Simian Virus Reactive Mutant SV40 Origin Friend Leukaemia Virus Neoplastic Cell Type 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer-Verlag Berlin · Heidelberg 1989

Authors and Affiliations

  • H.-W. Stürzbecher
    • 1
  • K. Rudge
    • 1
  • R. Brain
    • 1
  • C. Addison
    • 1
  • M. Grimaldi
    • 1
  • J. R. Jenkins
    • 1
  1. 1.Marie Curie Research InstituteOxted, SurreyUK

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