title: The p53 gene family.
abstract: p73 and p63 are two recently discovered p53 homologs. Like p53, these proteins can recognize canonical p53 DNA-binding sites and, when overproduced, can activate p53-responsive target genes and induce apoptosis. Unlike p53, these genes undergo complex alternative splicing which, at least in the case of p63, yields proteins with widely divergent biological properties. In addition p73 and p63 are, in contrast to p53, rarely mutated in human cancer. Furthermore, p73 inactivation is not required for viral transformation. Thus, there is currently no firm evidence that p63 and p73 should be considered tumor suppressors. The early suggestion that monoallelic expression of p73 contributed to carcinogenesis needs to be interpreted cautiously in light of data showing interindividual and intraindividual variation with respect to monoallelic expression of p73 and the finding that p73 mRNA levels are generally increased, rather than decreased, in a host of tumors relative to normal cells.
authors.affiliation: Howard Hughes Medical Institute and Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, MA 02115, USA. william_kaelin@dfci.harvard.edu
authors.forename: W G
authors.initials: WG
authors.lastname: Kaelin
mesh_terms: D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D020869:Gene Expression Profiling; D016147:Genes, Tumor Suppressor / Q000235:genetics / Q000502:physiology; D016158:Genes, p53; D006801:Humans; D008565:Membrane Proteins; D005810:Multigene Family; D009154:Mutation / Q000235:genetics; D009369:Neoplasms / Q000235:genetics / Q000628:therapy; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D009856:Oncogene Proteins, Viral / Q000378:metabolism; D010750:Phosphoproteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D011485:Protein Binding; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051736:Proto-Oncogene Proteins c-mdm2; D015534:Trans-Activators; D014157:Transcription Factors; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D025521:Tumor Suppressor Proteins
chemical_list: C081876:CKAP4 protein, human; D004268:DNA-Binding Proteins; D008565:Membrane Proteins; D009687:Nuclear Proteins; D009856:Oncogene Proteins, Viral; D010750:Phosphoproteins; D011518:Proto-Oncogene Proteins; C115051:TP63 protein, human; C000606460:TP73 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2