A paper to be published online by Nature challenges the conventional view of p53, a central protein in protecting against cancer. By switching the function of this protein on and off in mice, researchers have shown that its role in responding to DNA damage is irrelevant to protecting against a certain type of cancer induced by irradiation.
It was thought that one of the mechanisms by which p53 suppresses tumours was to respond to DNA damage and halt cell division or trigger cell death. Gerard Evan and his colleagues irradiated mice that had been genetically engineered to carry a p53 gene encoding a protein whose function can be switched on and off with a simple chemical treatment.
When p53 was switched on during irradiation it triggered the induction of cell death in DNA-damaged tissues, but did not protect the mice from developing lymphomas at a later time when compared to mice in which p53 remained switched off. Switching p53 on eight days after irradiation, however, protected the mice from cancer. This protection required a second tumour suppressor protein called p19ARF.
The results suggest that DNA-damage response and tumour suppression are unlinked functions of p53, each induced by different signals.
The results also suggest that the p53-dependent DNA-damage response causes much of the life-threatening tissue damage and side effects caused by radiation and chemotherapy - and that a brief dose of a drug that blocks p53 function during these treatments might prevent the unwanted effects while still maintaining tumour protection.
Gerard Evan (University of California, San Francisco, CA, USA)
Abstract available online.
(C) Nature press release.
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