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Human POMp75 is identified as the pro-oncoprotein TLS/FUS: both POMp75 and POMp100 DNA homologous pairing activities are associated to cell proliferation

Oncogene volume 18, pages 4515–4521 (1999)Cite this article

Abstract

We have previously developed an assay to measure DNA homologous pairing activities in crude extracts: The POM blot. In mammalian nuclear extracts, we detected two major DNA homologous pairing activities: POMp100 and POMp75. Here, we present the purification and identification of POMp75 as the pro-oncoprotein TLS/FUS. Because of the pro-oncogene status of TLS/FUS, we studied in addition, the relationships between cell proliferation and POM activities. We show that transformation of human fibroblasts by SV40 large T antigen results in a strong increase of both POMp100 and TLS/POMp75 activities. Although detectable levels of both POMp100 and TLS/POMp75 are observed in non-immortalized fibroblasts or lymphocytes, fibroblasts at mid confluence or lymphocytes stimulated by phytohaemaglutinin, show higher levels of POM activities. Moreover, induction of differentiation of mouse F9 line by retinoic acid leads to the inhibition of both POMp100 and TLS/POMp75 activities. Comparison of POM activity of TLS/FUS with the amount of TLS protein detected by Western blot, suggests that the POM activity could be regulated by post-translation modification. Taken together, these results indicate that POMp100 and TLS/POMp75 activitites are present in normal cells but are connected to cell proliferation. Possible relationship between cell proliferation, response to DNA damage and DNA homologous pairing activity of the pro-oncoprotein TLS/FUS are discussed.

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Acknowledgements

This work was supported by ARC and Electricité de France. We are grateful to D Rouillard (Institut Curie, Paris) for flow cytometry analysis, M Prosperi (Institut Curie, Paris) for c-myc expression analysis and to C Levalois for helpful technical assistance. We thank Drs J Coppey (Institut Curie, Paris) and A Sarrasin (IFC1, Villejuif) for providing us with the fibroblasts strains and their corresponding SV40 transformed lines and to D Ron (NYU) for the TLS cDNA and the 4H11 monoclonal anti-TLS antibody. Thanks are due to S Gangloff, P Radicella and J Smith for helpful discussions and critical reading of the manuscript.

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Author notes

  1. Alexandre T Akhmedov

    Present address: Basel Institute for Immunology, Grenzacherstrasse 487 Postfach, Basel, CH-4005, Switzerland

  2. Pascale Bertrand and Alexandre T Akhmedov: P Bertrand and AT Akhmedov contributed equally to this study

Authors and Affiliations

  1. CEA, DSV, DRR, CNRS UMR 217, 60-68 av. du Général Leclerc, Fontenay aux Roses, BP6, 92265, France

    Pascale Bertrand, Fabien Delacote & Bernard S Lopez

  2. Institut Curie, Section de Biologie, 26 rue d'Ulm, 75231, Paris, Cedex 05, France

    Pascale Bertrand, Alexandre T Akhmedov & Bernard S Lopez

  3. Groupe Hospitalier Bichat-Claude Bernard, 46 rue Henri Huchard, 75877, Paris, Cedex 18, France

    Antoine Durrbach

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Bertrand, P., Akhmedov, A., Delacote, F. et al. Human POMp75 is identified as the pro-oncoprotein TLS/FUS: both POMp75 and POMp100 DNA homologous pairing activities are associated to cell proliferation. Oncogene 18, 4515–4521 (1999). https://doi.org/10.1038/sj.onc.1203048

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