Role of the p53-homologue p73 in E2F1-induced apoptosis.
Most human cancers harbour aberrations of cell-cycle control, which result in deregulated activity of the E2F transcription factors with concomitant enhanced cell-cycle progression. Oncogenic signalling by E2F1 has recently been linked to stabilization and activation of the tumour suppressor p53 (refs 1,3,4). The p73 protein shares substantial sequence homology and functional similarity with p53 (refs 5-7 ). Hence, several previously considered p53-independent cellular activities may be attributable to p73. Here we provide evidence that E2F1 directly activates transcription of TP73, leading to activation of p53-responsive target genes and apoptosis. Disruption of p73 function by a tumour-derived p53 mutant reduced E2F1-mediated apoptosis. Thus, p73 activation by deregulated E2F1 activity might constitute a p53-independent, anti-tumorigenic safeguard mechanism.
Stiewe
T
T
Institute of Molecular Biology (Cancer Research), University of Essen, Medical School, Essen, Germany (FRG).
Pützer
B M
BM
D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics / Q000502:physiology*; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D019556:COS Cells; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D002460:Cell Line; D017931:DNA Primers / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000502:physiology*; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; D005786:Gene Expression Regulation / Q000187:drug effects; D016147:Genes, Tumor Suppressor; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics* / Q000502:physiology*; D011401:Promoter Regions, Genetic; D056465:Retinoblastoma-Binding Protein 1; D050680:Transcription Factor DP1; D014157:Transcription Factors / Q000378:metabolism / Q000494:pharmacology*; D015533:Transcriptional Activation; D014162:Transfection; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000502:physiology*; D025521:Tumor Suppressor Proteins; D020298:U937 Cells
C533431:Arid4a protein, mouse; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D017931:DNA Primers; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; C493754:E2f1 protein, mouse; D009687:Nuclear Proteins; D056465:Retinoblastoma-Binding Protein 1; C000606460:TP73 protein, human; D050680:Transcription Factor DP1; D014157:Transcription Factors; C000606368:Trp73 protein, mouse; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins