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c-Myc activation by Theileria parasites promotes survival of infected B-lymphocytes

Oncogene volume 24, pages 1075–1083 (2005)Cite this article

Abstract

Theileria parasites infect and transform bovine lymphocytes, but host cell immortalization is reversible, as upon parasite death the lymphocytes rapidly die of apoptosis. Infection leads to a marked augmentation in the levels of lymphocyte c-Myc, and the parasite achieves this by inducing increased c-myc transcription and by prolonging the half-life of the transcription factor. Reduction in c-Myc turnover can be ascribed to CK2-mediated phosphorylation of the transcription factor. A parasite-dependent GM-CSF autocrine loop activates a JAK2/STAT3 signalling pathway that contributes to heightened c-myc transcription, and inhibition of the pathway leads to caspase 9 activation and apoptosis that can be directly ascribed to a reduction in c-Myc. An antiapoptotic role for c-Myc was clearly demonstrated by specific inhibition of c-myc expression with antisense oligonucleotides, and this correlates with loss of the antiapoptotic protein Mcl-1, and, consistently, ectopic expression of c-Myc abrogates B-cell death induced upon JAK2 inhibition. Thus, Theileria parasites ensure the survival of their host lymphocytes via specific activation of c-Myc.

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Acknowledgements

We thank Marie Chaussepied, Victor Yuste and Angelita Rebollo for critical reading of the manuscript and helpful comments and Marie-Françoise Moreau for technical assistance. The dominant-negative JAK2 vectors were obtained from Olli Silvennoinen and STAT3 vectors were made by Toshio Hirano and obtained from Iris Behrmann. The c-myc-luciferase and E-box-luciferase plasmids were given by Dirk Eick and Michael Cole, and the CMV-c-Myc plasmid by Gail Sonenshein. FD was supported in part by the Pasteur-Weizmann Foundation, MB by a Swiss National Science Foundation fellowship, SH by a CROUS fellowship from the French Ministère de l'Education Nationale, de l'Enseignement Supérieur et de la Recherche and GL recognizes the support of the CNRS, the Pasteur Institute and the Pasteur-Weizmann Foundation.

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Authors and Affiliations

  1. Laboratoire de Signalisation Immunoparasitaire, CNRS URA CNRS 2581, Département de Parasitologie, Institut Pasteur, Batiment Elie Metchnikoff, 25-28 rue du Dr Roux, 75724, Paris, Cedex 15, France

    Frédéric Dessauge, Sophia Hilaly, Martin Baumgartner, Brigitte Blumen & Gordon Langsley

  2. Department of Stomatology, University of California, San Francisco, 513 Parnassus Ave., HSW 604, San Francisco, CA, 94143-0512, USA

    Martin Baumgartner

  3. The Royal Veterinary College, Hawkshead Lane, North Mymms, Hertfordshire, AL9 7TA, UK

    Dirk Werling

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  1. Frédéric Dessauge
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Correspondence to Gordon Langsley.

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Dessauge, F., Hilaly, S., Baumgartner, M. et al. c-Myc activation by Theileria parasites promotes survival of infected B-lymphocytes. Oncogene 24, 1075–1083 (2005). https://doi.org/10.1038/sj.onc.1208314

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