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ΔNp73 can modulate the expression of various genes in a p53-independent fashion

Oncogene volume 22, pages 8246–8254 (2003)Cite this article

Abstract

ΔNp73α is an isoform of the p53 homologue p73 that lacks an amino-terminal transactivation domain and antagonizes the induction of gene expression by p53. Here, we examined whether ΔNp73α might also modulate cellular transcription in the absence of p53. The expression of ΔNp73α in the p53−/− cell line H1299 reduced the mRNA levels of p21/CDKN1A, but did not affect other p53-responsive genes. Correspondingly, the p21/CDKN1A promoter was downregulated by ΔNp73α in reporter assays, whereas other p53-responsive promoters were not inhibited. To identify additional genes that respond to ΔNp73α in the absence of p53, microarrays carrying 4600 cDNA clones were hybridized. The expression of 30 genes was found to be altered more than threefold by overexpressed ΔNp73α. For instance, ΔNp73α increased the expression of EGR1 and CDC6, whereas it decreased the mRNA levels of c-MYC, cyclin A2/CCNA2, NF-κB1, ODC1, and RET finger protein/RFP. Semiquantitative reverse transcription–PCR confirmed these results and further revealed that the influence of ΔNp73α on the regulation of these genes differs from other p73 isoforms and p53. We conclude that the impact of ΔNp73α on gene expression is not limited to p53-responsive genes. Rather, ΔNp73α can regulate the expression of a variety of genes independently of p53.

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Acknowledgements

We thank H-D Klenk for continuous support. We are indebted to AJ Levine, C Prives and B Vogelstein for the generous gift of plasmids, antibodies and cells. We thank J Roth and the members of our group for helpful discussions. This work was supported by the Deutsche Krebshilfe/Dr Mildred Scheel Stiftung, the Wilhelm Sander Stiftung and the PE Kempkes Stiftung.

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Authors and Affiliations

  1. Institut für Virologie, Philipps-Universität Marburg, Robert Koch Str. 17, Marburg, 35037, Germany

    Natalia N Kartasheva, Claudia Lenz-Bauer & Matthias Dobbelstein

  2. Institute of Molecular Genetics, Russian Academy of Sciences, Kurchatov Sq. 46, Moscow, 123182, Russia

    Natalia N Kartasheva

  3. Institut für Medizinische Biometrie und Epidemiologie, Philipps-Universität Marburg, Bunsenstr. 3, Marburg, 35037, Germany

    Oliver Hartmann & Helmut Schäfer

  4. Institute of Molecular Biology and Tumor Research (IMT), Philipps-Universität Marburg, Emil-Mannkopff-Str. 2, Marburg, 35033, Germany

    Martin Eilers

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  1. Natalia N Kartasheva
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Correspondence to Matthias Dobbelstein.

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Kartasheva, N., Lenz-Bauer, C., Hartmann, O. et al. ΔNp73 can modulate the expression of various genes in a p53-independent fashion. Oncogene 22, 8246–8254 (2003). https://doi.org/10.1038/sj.onc.1207138

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