Mouse p53 inhibits SV40 origin-dependent DNA replication

Nature. 1987 Oct 1-7;329(6138):458-60. doi: 10.1038/329458a0.

Abstract

p53 is a cellular phosphoprotein that is present at elevated concentrations in cells transformed by different agents. p53 complementary DNA expression-constructs immortalize primary cells in vitro and co-operate with an activated ras oncogene in malignant transformation. Several reports have implicated p53 in mammalian cell cycle control and specifically with events occurring at the G0-G1 boundary. p53 forms specific complexes with simian virus 40 (SV40) large-T antigen, and such complexes are found associated with both replicating and mature SV40 DNA in lytically infected cells. In an accompanying paper Gannon and Lane report that in in vitro plate-binding assays, mouse p53 can displace polymerase alpha from complex with T-antigen. We have examined the in vivo consequences of expressing wild-type and mutant p53 proteins from other species in SV40-transformed monkey cells. We report here that expression of mouse p53 results in a substantial and selective inhibition of SV40 origin-dependent DNA replication. In addition to any function in the G0-G1 transition, the data presented suggest that p53 may affect directly the initiation or maintenance of replicative DNA synthesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Polyomavirus Transforming / metabolism
  • Cell Line
  • Cell Transformation, Viral
  • DNA Polymerase II / metabolism
  • DNA Replication*
  • DNA, Viral / biosynthesis*
  • Mice
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / physiology*
  • Phosphoproteins / genetics
  • Phosphoproteins / physiology*
  • Plasmids
  • Simian virus 40 / genetics*
  • Transfection
  • Tumor Suppressor Protein p53

Substances

  • Antigens, Polyomavirus Transforming
  • DNA, Viral
  • Neoplasm Proteins
  • Phosphoproteins
  • Tumor Suppressor Protein p53
  • DNA Polymerase II