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Tumour suppressors

The protective effect of arrest

Nature Reviews Cancer volume 4, page 92 (2004)Cite this article

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A TP53 point mutation has been found in human tumours that results in a protein that is unable to induce apoptosis, but is still able to induce arrest. The authors generated mice that were homozygous for an equivalent mutation: a guanine to cytosine mutation in base 515 of Trp53 — Trp53515C/515C — which corresponds to an arginine to proline amino-acid substitution at residue 172. They isolated mouse embryonic fibroblasts (MEFs) from these mice and treated them with γ-radiation. The Trp53515C/515C MEFs were better able to arrest than Trp53-null MEFs following γ-radiation, but did not arrest as effectively as wild-type MEFs. The extent of cell-cycle arrest correlated with the ability to induce expression of the cyclin-dependent kinase inhibitor Waf1.

As expected, the Trp53515C/515C MEFs were resistant to apoptosis that was induced by various conditions — exposure to doxorubicin and serum deprivation. Trp53515C/515C thymocytes were also resistant to apoptosis that was induced by γ-radiation, but were sensitive to apoptosis that was induced by dexamethasone, which operates through a p53-independent pathway.

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References

ORIGINAL RESEARCH PAPER

  1. Liu, G. et al. Chromosome stability, in the absence of apoptosis, is critical for suppression of tumorigenesis in Trp53 mutant mice. Nature Genet. 36, 63–68 (2004)

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FURTHER READING

  1. Vousden, K. H. & Lu, X. Live or let die: the cell's response to p53. Nature Rev. Cancer 2, 594–604 (2002)

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Authors
  1. Emma Greenwood
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Greenwood, E. The protective effect of arrest. Nat Rev Cancer 4, 92 (2004). https://doi.org/10.1038/nrc1284

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