title: p53 in polyoma virus transformed REF52 cells.
abstract: While cellular transformation by small DNA tumour viruses usually involves targeting the product of the p53 tumour suppressor gene by a virally encoded protein, none of the three polyoma virus (Py) specified T antigens have been observed to interact with p53. We show that primary mouse embryo fibroblasts and REF52 cells, which resemble primary cells in requiring co-operating oncogenes for transformation, cannot be transformed by the Py oncogene, middle T-antigen (PyMT), alone. These cells can be transformed by the complete Py early region, which encodes the Py large, middle and small T-antigens. We find that PyMT can transform rodent cells lacking a functional p53 protein (p53 null mouse embryo fibroblasts and DN-REF52 cells which contain a dominant negative p53). In Py transformed REF52 cells (Py-REF52) there is no significant accumulation of p53 protein, as opposed to SV40 transformed REF52 cells (SV-REF52) in which the amount of steady state p53 protein is elevated. However accumulation of p53 is observed following exposure of Py-REF52 cells to u.v. Treatment of Py-REF52 cells with X-rays results in a rapid increase in the levels of the p53-induced proteins p21/WAF1 and MDM2. In untransformed REF52 cells, X-irradiation causes p53 activation, which results in induction of both G1/S and G2/M blocks. In SV-REF52 and DN-REF52 cells, p53 abrogation results in the absence of both the G1/S and G2/M blocks. Only the absence of a G1/S block is observed in Py-REF52 cells exposed to X-irradiation. Together these results indicate that in contrast to most other DNA tumour viruses, Py does not appear to interfere with the DNA damage induced transactivation activities of the p53 protein but absence of a functional p53 protein can mediate transformation by the PyMT oncogene in the absence of other co-operating oncogenes. Possible modes of transformation by Py are discussed.
authors.affiliation: Eukaryotic Gene Organisation and Expression Laboratory, Imperial Cancer Research Fund, London.
authors.forename: O
authors.initials: O
authors.lastname: Mor
authors.forename: M
authors.initials: M
authors.lastname: Read
authors.forename: M
authors.initials: M
authors.lastname: Fried
mesh_terms: D000818:Animals; D002453:Cell Cycle / Q000528:radiation effects; D002472:Cell Transformation, Viral; D002478:Cells, Cultured; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000378:metabolism / Q000528:radiation effects; D004249:DNA Damage; D004622:Embryo, Mammalian; D005347:Fibroblasts / Q000528:radiation effects; D015972:Gene Expression Regulation, Neoplastic; D051379:Mice; D009687:Nuclear Proteins; D011120:Polyomavirus / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000378:metabolism / Q000528:radiation effects; D051736:Proto-Oncogene Proteins c-mdm2; D051381:Rats; D014170:Transformation, Genetic; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism* / Q000528:radiation effects
chemical_list: C493957:Cdkn1a protein, mouse; C493958:Cdkn1a protein, rat; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D016159:Tumor Suppressor Protein p53; C497207:Mdm2 protein, mouse; C497208:Mdm2 protein, rat; D051736:Proto-Oncogene Proteins c-mdm2