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Oncogene. 2005 Feb 3;24(6):1075-83.

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

Author information

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

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.

PMID:
15580287
DOI:
10.1038/sj.onc.1208314
[Indexed for MEDLINE]

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