Activation and activities of the p53 tumour suppressor protein.
The p53 tumour suppressor protein inhibits malignant progression by mediating cell cycle arrest, apoptosis or repair following cellular stress. One of the major regulators of p53 function is the MDM2 protein, and multiple forms of cellular stress activate p53 by inhibiting the MDM2-mediated degradation of p53. Mutations in p53, or disruption of the pathways that allow activation of p53, seem to be a general feature of all cancers. Here we review recent advances in our understanding of the pathways that regulate p53 and the pathways that are induced by p53, as well as their implications for cancer therapy.
Bálint E
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NCI at Frederick, National Institutes of Health, Building 560, Room 22-96, 1050 Boyles Street, Frederick, MD 21702-1201, USA.
Vousden
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KH
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002453:Cell Cycle / Q000502:physiology; D003546:Cysteine Endopeptidases / Q000378:metabolism; D004260:DNA Repair / Q000502:physiology; D016158:Genes, p53; D015316:Genetic Therapy; D006801:Humans; D019656:Loss of Heterozygosity; D008954:Models, Biological; D009097:Multienzyme Complexes / Q000378:metabolism; D009363:Neoplasm Proteins / Q000378:metabolism; D009369:Neoplasms / Q000378:metabolism / Q000628:therapy; D009687:Nuclear Proteins; D018384:Oxidative Stress; D010766:Phosphorylation; D046988:Proteasome Endopeptidase Complex; D011499:Protein Processing, Post-Translational; D011518:Proto-Oncogene Proteins / Q000502:physiology; D051736:Proto-Oncogene Proteins c-mdm2; D013312:Stress, Physiological / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D025803:Tumor Suppressor Protein p14ARF / Q000502:physiology; D016159:Tumor Suppressor Protein p53 / Q000172:deficiency / Q000502:physiology*
D009097:Multienzyme Complexes; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D025803:Tumor Suppressor Protein p14ARF; D016159:Tumor Suppressor Protein p53; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex