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p73 is transcriptionally regulated by DNA damage, p53, and p73

Abstract

p73 is a member of the p53 family. Recent studies have shown that DNA damage can stabilize p73 protein and enhance p73-mediated apoptosis in a c-Abl dependent manner. To determine what regulates p73 transcriptionally, we analysed the expression of p73 in several cell lines following genotoxic stresses. We found that p73 is induced in certain cell lines when treated with therapeutic DNA damaging agents. We also found that p53 and p73, but not mutant p53(R249S) and p73β292, directly induce the expression of the p73 gene. In addition, we found one potential p53-binding site in the promoter of the p73 gene. This binding site is responsive to p53, p73, and DNA damage. Taken together, these data suggest that p73 is transcriptionally regulated by DNA damage and p53, and is autoregulated.

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Acknowledgements

We are grateful to R Markowitz for critical reading of this manuscript. We would like to thank Dr C Harris (NIH) for providing the p73 BAC genomic DNA clone, and Drs C Prives and C Di Como (Columbia University) for providing rabbit anti-p73 antibody. This work is supported in part by Grant RO1 CA81237 and CA76069 from the National Institutes of Health and Grant DAMD 17-97-1-7019 from the United States DOD Breast Cancer Research Program.

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Chen, X., Zheng, Y., Zhu, J. et al. p73 is transcriptionally regulated by DNA damage, p53, and p73. Oncogene 20, 769–774 (2001). https://doi.org/10.1038/sj.onc.1204149

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