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A ribonucleotide reductase gene is a transcriptional target of p53 and p73

Abstract

Many p53-inducible genes have been identified that might play a role in mediating the various downstream activities of p53. We have identified a close relative of ribonucleotide reductase, recently named p53R2, as a p53-inducible gene, and show that this gene is activated by several stress signals that activate a p53 response, including DNA damaging agents and p14ARF. p53R2 expression was induced by p53 mutants that are defective for the activation of apoptosis, but retain cell cycle arrest function, although no induction of p53R2 was seen in response to p21WAF1/CIP1-mediated cell cycle arrest. Several isoforms of the p53 family member p73 were also shown to induce p53R2 expression. Transient ectopic expression of either wild type p53R2 or p53R2 targeted to the nucleus, did not significantly alter cell cycle progression in unstressed cells. The identification of this gene as a p53 target supports a direct role for p53 in DNA repair, in addition to inhibition of growth of damaged cells.

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Acknowledgements

We would like to thank Gerry Melino (University of Rome, Italy), for generously providing the human pcDNA-HAp73α, β and γ constructs, and Gordon Peters for the gift of NARF2 cells. We are extremely grateful to Andy Phillips, Kevin Ryan and all other members of the Vousden Lab for their invaluable help, advice and encouragement during the course of these studies.

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Nakano, K., Bálint, É., Ashcroft, M. et al. A ribonucleotide reductase gene is a transcriptional target of p53 and p73. Oncogene 19, 4283–4289 (2000). https://doi.org/10.1038/sj.onc.1203774

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