p53: at the crossroad between cancer and ageing.
The p53 tumour suppressor plays an undisputed role in cancer. p53's tumour suppressive activity stems from its ability to respond to a variety of stresses to trigger cell cycle arrest, apoptosis or senescence, thereby protecting against malignant transformation. An increasing body of evidence suggests that p53 also drives organismal ageing. Although genetic models with altered p53 function display age-related phenotypes and thus provide in vivo evidence that p53 contributes to the ageing process, p53's role in organismal ageing remains controversial. Anti-cancer therapies that target p53 and reactivate or enhance its activity are considered good alternatives for treating various neoplasms. Therefore, it is important to determine whether these clinical approaches compromise tissue homeostasis and contribute to ageing. This review presents a number of models with altered p53 function and discusses how these models implicate p53 as part of a molecular network that integrates tumour suppression and ageing.
Papazoglu
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Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.
Mills
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D000375:Aging / Q000235:genetics*; D000483:Alleles; D000818:Animals; D031204:Caloric Restriction; D016922:Cellular Senescence / Q000235:genetics; D004195:Disease Models, Animal; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D009369:Neoplasms / Q000235:genetics*; D009474:Neurons / Q000502:physiology; D011110:Polymorphism, Genetic / Q000235:genetics; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D037761:Sirtuins / Q000235:genetics; D019098:Telomerase / Q000172:deficiency; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
D016159:Tumor Suppressor Protein p53; D051736:Proto-Oncogene Proteins c-mdm2; D019098:Telomerase; D037761:Sirtuins