A role for both RB and p53 in the regulation of human cellular senescence

Exp Cell Res. 1991 Sep;196(1):33-9. doi: 10.1016/0014-4827(91)90453-2.


We present evidence for the possible involvement of both the RB and p53 proteins in the regulation of cellular senescence. Human fibroblasts immortalized with an inducible SV40 T-antigen become senescent following the de-induction of T-antigen. Plasmids expressing an alternative source of intact T-antigen restore proliferation but T-antigen deletion mutants lacking either the RB or p53 binding domains are unable to do so. Similarly, combinations of adenovirus E1A + E1B or human papillomavirus E6 + E7 genes are able to replace T-antigen functions and permit cell proliferation, whereas the individual genes do not. These results are discussed in terms of a two-stage model for the escape from in vitro cellular senescence.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenoviruses, Human / immunology
  • Antigens, Viral, Tumor / immunology
  • Cell Division / physiology
  • Cell Survival / physiology
  • Cells, Cultured
  • Genes, Viral / physiology
  • Humans
  • Lung / cytology*
  • Lung / immunology
  • Lung / physiology
  • Mutation / immunology
  • Papillomaviridae / immunology
  • Plasmids
  • Retinoblastoma Protein / metabolism
  • Retinoblastoma Protein / physiology*
  • Simian virus 40 / immunology
  • Tumor Suppressor Protein p53 / metabolism
  • Tumor Suppressor Protein p53 / physiology*


  • Antigens, Viral, Tumor
  • Retinoblastoma Protein
  • Tumor Suppressor Protein p53