Abstract
The tumour-suppressor gene p53 is frequently mutated in human cancers and is important in the cellular response to DNA damage1,2. Although the p53 family members p63 and p73 are structurally related to p53, they have not been directly linked to tumour suppression, although they have been implicated in apoptosis3,4,5,6,7,8,9. Given the similarity between this family of genes and the ability of p63 and p73 to transactivate p53 target genes10,11, we explore here their role in DNA damage-induced apoptosis. Mouse embryo fibroblasts deficient for one or a combination of p53 family members were sensitized to undergo apoptosis through the expression of the adenovirus E1A oncogene12,13,14. While using the E1A system facilitated our ability to perform biochemical analyses, we also examined the functions of p63 and p73 using an in vivo system in which apoptosis has been shown to be dependent on p53. Using both systems, we show here that the combined loss of p63 and p73 results in the failure of cells containing functional p53 to undergo apoptosis in response to DNA damage.
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Change history
26 May 2023
Editor’s Note: Readers are alerted that the reliability of data presented in this manuscript is currently in question. Appropriate editorial action will be taken once this matter is resolved.
28 February 2024
An Editorial Expression of Concern to this paper has been published: https://doi.org/10.1038/s41586-024-07223-4
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Acknowledgements
We thank J. Sage for critical reading of the manuscript, W. G. Kaelin and M. S. Irwin for human TAp73α mammalian expression vector, L. Attardi for PERP cDNA, D. MacPherson for helpful discussions, and K. Olive for p53+/- mice. This work was supported in part by the NIH and Howard Hughes Medical Institute. E.R.F. is a postdoctoral fellow of the Leukemia and Lymphoma Society of America. K.Y.T. is supported by the Medical Scientist Training Program and a Koch graduate fellowship. T.J. is an Associate Investigator of the Howard Hughes Medical Institute.
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Flores, E., Tsai, K., Crowley, D. et al. p63 and p73 are required for p53-dependent apoptosis in response to DNA damage. Nature 416, 560–564 (2002). https://doi.org/10.1038/416560a
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DOI: https://doi.org/10.1038/416560a
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