Divorcing ARF and p53: an unsettled case.
Mammalian cells that sustain oncogenic insults can invoke defensive programmes that either halt their division or trigger their apoptosis, but these countermeasures must be finely tuned to discriminate between physiological and potentially harmful growth-promoting states. By functioning specifically to oppose abnormally prolonged and sustained proliferative signals produced by activated oncogenes, the ARF tumour suppressor antagonizes functions of MDM2 to induce protective responses that depend on the p53 transcription factor and its many target genes. However, ARF has been reported to physically associate with proteins other than MDM2 and to have p53-independent activities, most of which remain controversial and poorly understood.
Sherr
Charles J
CJ
Howard Hughes Medical Institute, St. Jude Children's Research Hospital, 332 North Lauderdale, Memphis, Tennessee 38105, USA. sherr@stjude.org
D000818:Animals; D017209:Apoptosis; D006801:Humans; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology; D051736:Proto-Oncogene Proteins c-mdm2 / Q000037:antagonists & inhibitors; D015398:Signal Transduction; D025803:Tumor Suppressor Protein p14ARF / Q000502:physiology*; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*
D025803:Tumor Suppressor Protein p14ARF; D016159:Tumor Suppressor Protein p53; D051736:Proto-Oncogene Proteins c-mdm2