title: A role for both RB and p53 in the regulation of human cellular senescence.
abstract: 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.
authors.affiliation: Department of Cell Biology and Neuroscience, University of Texas, Southwestern Medical Center, Dallas 75235.
authors.forename: J W
authors.initials: JW
authors.lastname: Shay
authors.forename: O M
authors.initials: OM
authors.lastname: Pereira-Smith
authors.forename: W E
authors.initials: WE
authors.lastname: Wright
mesh_terms: D000260:Adenoviruses, Human / Q000276:immunology; D000957:Antigens, Viral, Tumor / Q000276:immunology; D002455:Cell Division / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D005814:Genes, Viral / Q000502:physiology; D006801:Humans; D008168:Lung / Q000166:cytology* / Q000276:immunology / Q000502:physiology; D009154:Mutation / Q000276:immunology; D027383:Papillomaviridae / Q000276:immunology; D010957:Plasmids; D016160:Retinoblastoma Protein / Q000378:metabolism / Q000502:physiology*; D013539:Simian virus 40 / Q000276:immunology; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism / Q000502:physiology*
chemical_list: D000957:Antigens, Viral, Tumor; D016160:Retinoblastoma Protein; D016159:Tumor Suppressor Protein p53