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Ets-1 p27: a novel Ets-1 isoform with dominant-negative effects on the transcriptional properties and the subcellular localization of Ets-1 p51

Oncogene volume 28, pages 2087–2099 (2009)Cite this article

Abstract

The transcription factor Ets-1 is implicated in various physiological processes and invasive pathologies. We identified a novel variant of ets-1, ets-1Δ(III–VI), resulting from the alternative splicing of exons III to VI. This variant encodes a 27 kDa isoform, named Ets-1 p27. Ets-1 p27 lacks the threonine-38 residue, the Pointed domain and the transactivation domain, all of which are required for the transactivation of Ets-1 target genes. Both inhibitory domains surrounding the DNA-binding domain are conserved, suggesting that Ets-1 p27, like the full-length Ets-1 p51 isoform, is autoinhibited for DNA binding. We showed that Ets-1 p27 binds DNA in the same way as Ets-1 p51 does and that it acts both at a transcriptional and a subcellular localization level, thereby constituting a dual-acting dominant negative of Ets-1 p51. Ets-1 p27 blocks Ets-1 p51-mediated transactivation of target genes and induces the translocation of Ets-1 p51 from the nucleus to the cytoplasm. Furthermore, Ets-1 p27 overexpression represses the tumor properties of MDA-MB-231 mammary carcinoma cells in correlation with the known implication of Ets-1 in various cellular mechanisms. Thus the dual-acting dominant-negative function of Ets-1 p27 gives to the Ets-1 p27/Ets-1 p51 ratio a determining effect on cell fate.

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Acknowledgements

We thank Isabelle Roland, Anne-Claire Flourens, Nathalie Tomavo and Arnaud Legrand for technical assistance, and Dr Yvan de Launoit for stimulating discussions. We thank the Microscopy Facility of the Institut Pasteur de Lille Campus. This work was supported by the Centre National de la Recherche Scientifique (CNRS) and by grants from la Ligue contre le Cancer-Comité du Pas-de-Calais and from the Fondation pour la Recherche Médicale-Comité Nord-Pas-de-Calais (FRM). The Ministère de la Recherche et de l’Enseignement Supérieur provided a student fellowship to Clélia Laitem. La Ligue contre le Cancer provided a student fellowship to Gabriel Leprivier. The CNRS and the Conseil Régional du Nord-Pas-de-Calais provided a PhD fellowship (BDI) to Souhaila Choul-li.

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  1. G Leprivier

    Present address: 3Current address: Department of Molecular Oncology, British Columbia Cancer Research Centre, Vancouver, British Columbia, Canada.,

  2. C Laitem and G Leprivier: These authors contributed equally to this work.

Authors and Affiliations

  1. CNRS Unité Mixte de Recherche 8161, Institut de Biologie de Lille, Institut Pasteur de Lille, Universités de Lille 1 and Lille 2, IFR 142, Lille, France

    C Laitem, G Leprivier, S Choul-Li, A Begue, D Monte, P Dumont, M Duterque-Coquillaud & M Aumercier

  2. Department of Pathology, Institut Jules Bordet, Brussels, Belgium

    D Larsimont

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Laitem, C., Leprivier, G., Choul-Li, S. et al. Ets-1 p27: a novel Ets-1 isoform with dominant-negative effects on the transcriptional properties and the subcellular localization of Ets-1 p51. Oncogene 28, 2087–2099 (2009). https://doi.org/10.1038/onc.2009.72

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