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Parsing p53 activity

Chromosome instability (left) is not a problem for cells with a p53 point mutation (right). Lozano/Macmillan

Vvertebrate p53 has many talents, including the ability to induce apoptosis and cell cycle arrest in response to DNA damage. At least one of these talents seems to be crucial for suppressing tumor formation, as mice that lack p53 develop early onset T-cell lymphomas and usually die young. New results from Geng Liu, Guillermina Lozano, and colleagues (M.D. Anderson Cancer Center, Houston, Texas) suggest that, for tumor initiation, delay trumps death.

The group made mice with a p53 point mutation that leaves the protein with the ability to delay cell cycle but not induce apoptosis. This mutation causes a much less severe phenotype than p53 deletions, with a long delay in tumor onset and only rare cases of lymphoma. They then showed that the decreased tumorigenesis is a result of the p53 cell cycle activity's ability to maintain genome stability. Most of the tumor cells from p53 null mice were aneuploid, but those from mice with the point mutation remained diploid. The point mutation cells also had two centrosomes during division, whereas the null cells had multiple centrosomes that led to large chromosomal breaks and missegregations.

"If you look at the literature, it is almost dogma that the apoptosis function of p53 is the crucial activity for preventing tumorigenesis," says Lozano. "Our data says that the cell cycle arrest function of p53 is as pivotal." The tumors that do develop, however, tend to be aggressive, which supports the idea that apoptosis is critical for controlling tumor progression.

Reference:

Liu, G., et al. 2004. Nat. Genet. 36:63–68.[CrossRef][Medline]

Rabiya Tuma

rabiya{at}nasw.org

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This Article Full Text (PDF, 411K) PPT slides of all figures Alert me when this article is cited Services Email this article Similar articles in this journal Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Tuma, R. Search for Related Content PubMed Articles by Tuma, R. Social Bookmarking                            What's this?