title: Oncogenes induce and activate endogenous p73 protein.
abstract: The identification of upstream pathways that signal to TP73 is crucial for understanding the biological role of this gene. Since some evidence suggests that TP73 might play a role in tumorigenesis, we asked whether oncogenes can induce and activate endogenous TP73. Here, we show that endogenous p73 alpha and beta proteins are up-regulated in p53-deficient tumor cells in response to overexpressed E2F1, c-Myc, and E1A. E2F1, c-Myc, and E1A-mediated p73 up-regulation leads to activation of the p73 transcription function, as shown by p73-responsive reporter activity and by induction of known endogenous p73 target gene products such as p21 and HDM2. Importantly, E2F1-, c-Myc-, and E1A-mediated activation of endogenous p73 induces apoptosis in SaOs-2 cells. Conversely, inactivation of p73 by a dominant negative p73 inhibitor (p73DD), but not by a mutant p73DD, inhibits oncogene-induced apoptosis. These data show that oncogenes can signal to TP73 in vivo. Moreover, in the absence of p53, oncogenes may enlist p73 to induce apoptosis in tumor cells.
authors: Department of Pathology, State University of New York at Stony Brook, Stony Brook, New York 11794-8691, USA.
authors: A
authors: A
authors: Zaika
authors: M
authors: M
authors: Irwin
authors: C
authors: C
authors: Sansome
authors: U M
authors: UM
authors: Moll
mesh_terms: D017500:Adenovirus E1A Proteins / Q000235:genetics; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins / Q000235:genetics*; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D016259:Genes, myc; D006801:Humans; D009687:Nuclear Proteins / Q000235:genetics*; D009857:Oncogenes; D056465:Retinoblastoma-Binding Protein 1; D050680:Transcription Factor DP1; D014157:Transcription Factors / Q000235:genetics; D014407:Tumor Cells, Cultured; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins
chemical_list: D017500:Adenovirus E1A Proteins; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; D009687:Nuclear Proteins; D056465:Retinoblastoma-Binding Protein 1; C000606460:TP73 protein, human; D050680:Transcription Factor DP1; D014157:Transcription Factors; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins