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Identification of Tcf-4 as a transcriptional target of p53 signalling

Oncogene volume 23, pages 3376–3384 (2004)Cite this article

Abstract

T-cell factor (Tcf)-4 is a main transcription factor to pass on Wnt/β-catenin signalling. The tumour suppressor protein p53 contributes as a transcription factor to cell-cycle arrest and apoptosis induction. Mutations of components in p53 and Wnt/β-catenin signalling networks play a part in tumour formation. Here, we identify the Tcf-4 gene as a downstream effector of p53. Induction of wild-type p53 in a tet-off regulated human colon cell system leads to the reduction of Tcf-4 mRNA and protein levels. Also, mRNA of the Tcf-4 target gene uPAR is downregulated after p53 induction. Expression of a luciferase reporter controlled by the Tcf-4 promoter is repressed by wild-type p53, but not by a p53 mutant deficient in DNA binding. Such a regulation is seen in cell lines of different origin. These findings directly link Wnt/β-catenin signalling and p53 tumour suppressor function and may provide a mechanism by which loss of p53 function contributes to progression in the adenoma/carcinoma sequence in colon tumours. Furthermore, since Tcf-4 is expressed in many tissues and downregulation of Tcf-4 by p53 is seen in several different cell types, this regulation likely plays a role in proliferation control of all tissues that can express p53 and Tcf-4.

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Acknowledgements

We thank Jana Lorenz for technical support, Jutta Jahns for assistance with the cell irradiation experiments, Matthias Dobbelstein for comments on the data and Hans Clevers and Bert Vogelstein for generously providing reagents and cells. KR and KT were recipients of graduate fellowships awarded by the Freistaat Sachsen. KE is supported by grants from the Bundesministerium für Bildung und Forschung, the Interdisciplinary Centre for Clinical Research (IZKF) at the University of Leipzig and the Deutsche Forschungsgemeinschaft.

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Authors and Affiliations

  1. Medizinische Klinik und Poliklinik II, Max-Bürger-Forschungszentrum, Universität Leipzig, Johannisallee 30, Leipzig, D-04103, Germany

    Karen Rother, Cindy Johne, Katja Spiesbach, Ulrike Haugwitz, Katrin Tschöp, Mark Wasner, Joachim Mössner & Kurt Engeland

  2. Institut für Zellbiologie, Universitätsklinikum Essen, Virchowstraße 173, Essen, D-45122, Germany

    Ludger Klein-Hitpass & Tarik Möröy

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  1. Karen Rother
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Correspondence to Kurt Engeland.

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Rother, K., Johne, C., Spiesbach, K. et al. Identification of Tcf-4 as a transcriptional target of p53 signalling. Oncogene 23, 3376–3384 (2004). https://doi.org/10.1038/sj.onc.1207464

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