Oncogenes Induce and Activate Endogenous p73 Protein

Alexander Zaika, Meredith Irwin, Christine Sansome, Ute M. Moll

Research output: Contribution to journalArticle

122 Citations (Scopus)

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 α and β proteins are upregulated 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.

Original languageEnglish (US)
Pages (from-to)11310-11316
Number of pages7
JournalJournal of Biological Chemistry
Volume276
Issue number14
DOIs
StatePublished - Apr 6 2001
Externally publishedYes

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Oncogenes
Apoptosis
Tumors
Genes
Chemical activation
Cells
Proteins
Transcription
Transcriptional Activation
Signal Transduction
Neoplasms
Carcinogenesis
Up-Regulation
Tumor Protein p73

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Oncogenes Induce and Activate Endogenous p73 Protein. / Zaika, Alexander; Irwin, Meredith; Sansome, Christine; Moll, Ute M.

In: Journal of Biological Chemistry, Vol. 276, No. 14, 06.04.2001, p. 11310-11316.

Research output: Contribution to journalArticle

Zaika, Alexander ; Irwin, Meredith ; Sansome, Christine ; Moll, Ute M. / Oncogenes Induce and Activate Endogenous p73 Protein. In: Journal of Biological Chemistry. 2001 ; Vol. 276, No. 14. pp. 11310-11316.
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