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Cytoplasmic functions of the tumour suppressor p53

Abstract

The principal tumour-suppressor protein, p53, accumulates in cells in response to DNA damage, oncogene activation and other stresses. It acts as a nuclear transcription factor that transactivates genes involved in apoptosis, cell cycle regulation and numerous other processes. An emerging area of research unravels additional activities of p53 in the cytoplasm, where it triggers apoptosis and inhibits autophagy. These previously unknown functions contribute to the mission of p53 as a tumour suppressor.

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Figure 1: Classification of p53 activities.
Figure 2: Interplay of the nuclear and cytoplasmic functions of p53 in apoptosis.
Figure 3: Concerted oncogenic actions of mutant p53 or inactive ARF in the nucleus and cytoplasm of cancer cells.

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Acknowledgements

Acknowledgments The authors’ own work is supported by NIH and the American Lebanese and Syrian Associated Charities (to D.R.G.) and by Ligue contre le Cancer, INCa, Cancéropole, ANR, ANRS and the Active p53 and Apo-Sys EU networks (to G.K.).

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Correspondence to Douglas R. Green or Guido Kroemer.

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Green, D., Kroemer, G. Cytoplasmic functions of the tumour suppressor p53. Nature 458, 1127–1130 (2009). https://doi.org/10.1038/nature07986

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