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DNA binding and selective gene induction by different forms of the p53 protein

Oncogene volume 26, pages 2955–2963 (2007)Cite this article

Abstract

P53 is a tumor suppressor gene that plays a crucial role in suppressing tumorigenesis by inducing either cell cycle arrest or apoptosis in cells with DNA damage. In more than 50% of tumors p53 is inactivated by gene mutations. However, there have also been reports of tumor cells in which p53 remains wild type and is present in elevated concentrations. Here we utilized a set of mutant cell lines, which, unlike the parental A1-5 cell line, which expresses a mouse tsp53 and becomes growth arrested at 32°C, are capable of growth at this same incubation temperature. We found that the tsp53 in the two cell lines, ALTR-17 and ALTR-24, was identical to the parental A1-5s and concentrated in the nucleus at 32°C. Examination of both lines revealed that p21 was induced at 32°C, although to a lesser extent than in parental cells and that the p21 genes were not mutated. Interestingly, evaluation of the conformation of tsp53 using conformation-specific antibodies showed that the protein existed in different forms, which were found to bind DNA using chromatin immunoprecipitation assays and which we showed could induce expression of a p21 reporter construct. We conclude that the tsp53 may exist in various forms capable of binding DNA.

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Acknowledgements

We thank Dr Bert Vogelstein for providing the WWP-luc plasmid and Dr Moshe Oren for the Mdm2-luc plasmid and Dr Cyrus Vaziri for providing the Ad-p21. This work was supported by the National Institutes of Health Grant CA090776 awarded to JDM.

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Authors and Affiliations

  1. Genetics Graduate Interdisciplinary Program, University of Arizona, Tucson, AZ, USA

    F Mayelzadeh & J D Martinez

  2. Arizona Cancer Center, University of Arizona, Tucson, AZ, USA

    F Mayelzadeh & J D Martinez

  3. Department of Cell Biology and Anatomy, University of Arizona, Tucson, AZ, USA

    J D Martinez

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  1. F Mayelzadeh
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  2. J D Martinez
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Correspondence to J D Martinez.

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Mayelzadeh, F., Martinez, J. DNA binding and selective gene induction by different forms of the p53 protein. Oncogene 26, 2955–2963 (2007). https://doi.org/10.1038/sj.onc.1210110

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