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p53 is required for radiation-induced apoptosis in mouse thymocytes

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Abstract

THE p53 tumour suppressor gene is the most widely mutated gene in human tumorigenesis1,2. p53 encodes a transcriptional activator3–7 whose targets may include genes that regulate genomic stability8,9, the cellular response to DNA damage10,11, and cell-cycle progression12,13. Introduction of wild-type p53 into cell lines that have lost endogenous p53 function can cause growth arrest14–16 or induce a process of cell death known as apoptosis17,18. During normal development, self-reactive thymocytes undergo negative selection by apoptosis19, which can also be induced in immature thymocytes by other stimuli, including exposure to glucocorticoids15 and ionizing radiation16. Although normal negative selection involves signalling through the T-cell receptor14, the induction of apoptosis by other stimuli is poorly understood. We have investigated the requirement for p53 during apoptosis in mouse thymocytes. We report here that immature thymocytes lacking p53 die normally when exposed to compounds that may mimic T-cell receptor engagement and to glucocorticoids but are resistant to the lethal effects of ionizing radiation. These results demonstrate that p53 is required for radiation-induced cell death in the thymus but is not necessary for all forms of apoptosis.

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Authors and Affiliations

  1. Department of Biology, Center for Cancer Research, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts, 02139, USA

    Scott W. Lowe, Earlene M. Schmitt & Tyler Jacks

  2. Department of Veterinary and Animal Sciences,

    Sallie W. Smith & Barbara A. Osborne

  3. Program in Molecular and Cellular Biology, 309 Paige Laboratory, University of Massachusetts, Amherst, Massachusetts, 01003, USA

    Barbara A. Osborne

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  1. Scott W. Lowe
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  2. Earlene M. Schmitt
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  4. Barbara A. Osborne
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  5. Tyler Jacks
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Lowe, S., Schmitt, E., Smith, S. et al. p53 is required for radiation-induced apoptosis in mouse thymocytes. Nature 362, 847–849 (1993). https://doi.org/10.1038/362847a0

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  • DOI: https://doi.org/10.1038/362847a0

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