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The first 30 years of p53: growing ever more complex

Abstract

Thirty years ago p53 was discovered as a cellular partner of simian virus 40 large T-antigen, the oncoprotein of this tumour virus. The first decade of p53 research saw the cloning of p53 DNA and the realization that p53 is not an oncogene but a tumour suppressor that is very frequently mutated in human cancer. In the second decade of research, the function of p53 was uncovered: it is a transcription factor induced by stress, which can promote cell cycle arrest, apoptosis and senescence. In the third decade after its discovery new functions of this protein were revealed, including the regulation of metabolic pathways and cytokines that are required for embryo implantation. The fourth decade of research may see new p53-based drugs to treat cancer. What is next is anybody's guess.

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Figure 1: Simplified scheme of the p53 pathway.

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Acknowledgements

We wish to thank the thousands of researchers whose outstanding work over the past 30 years has made p53 research so exciting. We apologize to all our colleagues whose important contributions could not be cited owing to lack of space. Work in the authors' laboratories is supported by grant R37 CA40099 from the National Cancer Institute, USA, a Center of Excellence grant from the Flight Attendant Medical Research Institute, USA, grants from the European Commission (Mutp53, FP6 Contract 502983 and OncomiRs, FP7 Contract 201102) and the Robert Bosch Foundation, Germany, (to M.O.), grant PO1 CA 87497 from the US National Institutes of Health, grant W81XWH-06-1-0514 from the Department of Defense, USA, grants from the Breast Cancer Research Foundation, USA,(to A.J.L.) and general support from the Simons Center for Systems Biology at the Institute for Advanced Study from the Simons Foundation, USA.

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Levine, A., Oren, M. The first 30 years of p53: growing ever more complex. Nat Rev Cancer 9, 749–758 (2009). https://doi.org/10.1038/nrc2723

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