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The N-terminal domain of human TAFII68 displays transactivation and oncogenic properties

Oncogene volume 18, pages 8000–8010 (1999)Cite this article

Abstract

In Ewing tumor, the (11;22) chromosomal translocation produces a chimeric molecule composed of the amino-terminal domain of EWS fused to the carboxyl-terminal DNA-binding domain of FLI-1. Previously, we have identified a novel protein TAFII68, which is highly similar to EWS and another closely related protein TLS (also called FUS). We demonstrate that the N-terminus of TAFII68 efficiently stimulates transcription when fused to two different DNA binding domains and that overexpression of TAFII68-FLI-1 chimeras in NIH3T3 cells leads to oncogenic transformation. We have also investigated the molecular mechanisms which could account for the transcriptional activation and the oncogenic transformation potential of the N-termini of TAFII68 and EWS. Thus, we have tested whether the artificial recruitment of components of the preinitiation complex (PIC) or a histone acetyltransferase (HAT) could bypass the requirement for the activation domains of either EWS or TAFII68. Recruitment of individual components of the transcription machinery or the GCN5 HAT is not sufficient to promote activation from FLI-1 responsive genes either in transfection experiments or in oncogenic transformation assays. These results suggest that the TAFII68 or EWS activation domains enhance a step after PIC formation in the transcriptional activation process.

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Acknowledgements

We thank P Chambon for his continuous support. We are grateful to A Boureux, J Ghysdael and S Casarosa for the kind gift of reagents and very useful advice; I Davidson, M Vigneron, O Delattre, H Kovar, R Petermann and S Berger for cDNAs encoding hTAFII28, hRPB3, hRPB7, EWS, FLI-1 and hGCN5-S and the anti-FLI-1 antibody; C Werlé and B Boulay for illustrations and photography. A Bertolotti was supported by a fellowship from Association pour la Recherche contre le Cancer, B Bell was supported by fellowships from Fondation pour la Recherche Médicale and Institut National de la Santé et de la Recherche Médicale (INSERM). This work was supported by funds from the INSERM, the Centre National de la Recherche Scientifique (CNRS), the Hópital Universitaire de Strasbourg, the Association pour la Recherche sur le Cancer (ARC), the Fondation pour la Recherche Médicale (FRM), the Ligue Nationale Contre le Cancer and the Comité Départemental du Haut-Rhin de la Ligue National Contre le Cancer.

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  1. Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP, BP 163 - 67404 Illkirch Cedex, CU de Strasbourg, France

    Anne Bertolotti, Brendan Bell & Làszlò Tora

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Bertolotti, A., Bell, B. & Tora, L. The N-terminal domain of human TAFII68 displays transactivation and oncogenic properties. Oncogene 18, 8000–8010 (1999). https://doi.org/10.1038/sj.onc.1203207

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