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Physical and functional cooperation between AP-1 and β-catenin for the regulation of TCF-dependent genes

Oncogene volume 26, pages 3492–3502 (2007)Cite this article

Abstract

Stabilization of cytoplasmic β-catenin is a hallmark of a variety of cancers. The stabilized β-catenin is able to translocate to the nucleus, where it acts as a transcriptional activator of T-cell factor (TCF)-regulated genes. β-Catenin may cross-talk with many signalling cascades to activate target genes. Whether β-catenin cooperates with AP-1, another transcriptional complex activated during tumorigenesis is not fully clarified. We show that β-catenin co-immunoprecipitates with c-Jun and c-Fos. GST pull-down experiments indicate a physical association of the armadillo repeat domain of β-catenin with the DNA-binding domain of c-Jun and of the C-terminal domain of β-catenin with the N-terminal domain of c-Fos. Promoter studies indicate that overexpression of AP-1 activates the transcription of two β-catenin target genes, cyclin D1 and c-myc, by a mechanism independent of the AP-1 site, and fully dependent on the TCF-binding site. We further demonstrate that AP-1/β-catenin synergism is involved during serum-induced cyclin D1 transcriptional activation. We identify a TCF-binding site on the cyclin D1 promoter which binds in vivo a complex induced by serum, containing β-catenin, TCF4, c-Fos, c-Jun, JunB and JunD. This novel mechanism of interaction between two signalling cascades might contribute to the potentiation of malignancy.

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Acknowledgements

We thank Franck Verecchia and Jean-Luc Poyet (INSERM U697) for helpful discussions, Cécile Pouzet (IFR02, Paris, France) and Niclas Setterblad (IFR105, Paris, France) for assistance and access to the confocal microscope, Jocelyne André for help in PCR assays, and Agnès Legrand for expert technical assistance. KT was supported by a doctoral fellowship from the Agence Nationale pour la Recherche contre le SIDA (ANRS), MCG by a doctoral fellowship from the Ministry of Research and Technologies (MRT) and JLM by a post-doctoral fellowship from INSERM. This work was supported by INSERM and by a grant from ANRS.

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Authors and Affiliations

  1. INSERM, U697, Paris, France

    K Toualbi, M C Güller, J-L Mauriz, A Mauviel & D Bernuau

  2. Université Paris 7 Denis Diderot, Paris, France

    K Toualbi, M C Güller, J-L Mauriz, A Mauviel & D Bernuau

  3. Institut Pasteur, Unité de Recombinaison et Expression Génétique, Paris, France

    C Labalette & M-A Buendia

  4. INSERM, U163, Paris, France

    C Labalette & M-A Buendia

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  1. K Toualbi
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  2. M C Güller
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Correspondence to D Bernuau.

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Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc).

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Toualbi, K., Güller, M., Mauriz, JL. et al. Physical and functional cooperation between AP-1 and β-catenin for the regulation of TCF-dependent genes. Oncogene 26, 3492–3502 (2007). https://doi.org/10.1038/sj.onc.1210133

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