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Differential regulation of p63 and p73 expression

Oncogene volume 22, pages 5686–5693 (2003)Cite this article

Abstract

Two homologs of the tumor suppressor p53, named p63 and p73, are each expressed from at least two start sites of mRNA synthesis, yielding full-length, transactivating (TA) isoforms, and also aminoterminally truncated (ΔN) isoforms that act as antagonists to p53. The expression of TAp73-transcripts is induced by E2F and negatively regulated by transforming growth factor β (TGFβ). The ΔNp73 promoter is induced by p53, resulting in negative feedback to control p53 activity. Here, we have analysed the expression of p63 in comparison with p73. In contrast to the induction of ΔNp73, the expression of ΔNp63 was reduced by p53 particularly in human keratinocytes, at the mRNA and protein levels. Accordingly, the 3′ promoter of p73, but not that of p63, was activated by p53 in reporter assays. ΔNp73 mRNA and ΔNp73 protein, but not the p63 gene products, also accumulated when HaCat cells (lacking functional p53) were grown to high density. TAp73, but not TAp63, expression was suppressed by TGFβ in these cells, and the TAp73, but not the TAp63, promoter was induced by E2F-1. Thus, in contrast to the functional similarities of their respective products, the expression levels of p63 and p73 are regulated by different mechanisms. This might be responsible for the discordant biological roles of p63 and p73 in development, as well as their deviant expression characteristics in cancer.

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Acknowledgements

We thank H-D Klenk for continuous support. We are indebted to S Gaubatz, AJ Levine, F McKeon, B Pützer, 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 Deutsche Forschungsgemeinschaft, and the PE Kempkes Stiftung.

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Authors and Affiliations

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

    Angelika Waltermann, Natalia N Kartasheva & Matthias Dobbelstein

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

    Natalia N Kartasheva

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  1. Angelika Waltermann
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Correspondence to Matthias Dobbelstein.

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Waltermann, A., Kartasheva, N. & Dobbelstein, M. Differential regulation of p63 and p73 expression. Oncogene 22, 5686–5693 (2003). https://doi.org/10.1038/sj.onc.1206859

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