Two groups of researchers have isolated functional truncated mutant forms of p53 with a wild-type allele in two different model systems, worm and mouse. Their observations bear similarities and differences that both hone and expand the role of this pivotal protein in homeostatic mechanisms. Nikki Holbrook, professor, Internal Medicine and Geriatrics at Yale University Medical School, points out in her F1000 commentary, "These findings are likely to prompt a large number of new investigations on the role of p53 in aging and its link to other putative mechanisms in the aging process, including stress responsiveness/resistance."
Following an unexpected stem cell recombination event, Donehower generated mice with one wild-type p53 allele and a defective p53 allele. The mutant allele expresses a truncated RNA encoding a carboxy-terminal p53 fragment. The surprising results produced a give-and-take situation: there was increased activity of p53 and therefore enhanced resistance to tumor formation, but the mice ...
