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Cytoplasmic sequestration of p53 promotes survival in leukocytes transformed by Theileria

Oncogene volume 29, pages 3079–3086 (2010)Cite this article

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Abstract

The function of the p53 protein as the central effector molecule of the p53 apoptotic pathway was investigated in a reversible model of epigenetic transformation. The infection of bovine leukocytes by the intracellular protozoan parasite Theileria annulata results in parasite-dependent transformation and proliferation of the host cells. We found p53 to be largely localized in the host cell cytoplasm and associated with the parasite membrane of isolated schizonts. Curing infected cells of the parasite with the theilericidal drug buparvaquone resulted in a time-dependent translocation of p53 into the host cell nucleus and the upregulation of the proapoptotic Bax and Apaf-1 and the downregulation of the anti-apoptotic Bcl-2 proteins. Although buparvaquone treatment led to apoptosis of the host cell, inhibition of either p53 or Bax significantly reduced buparvaquone-induced apoptosis of the transformed cells. Thus, the p53 apoptotic pathway of host cells is not induced by infection and transformation with Theileria by a mechanism involving cytoplasmic sequestration of p53. The close association of host cell p53 with the parasite membrane implies that the parasite either interacts directly with p53 or mediates cytoplasmic sequestration of p53 by interacting with other host cell proteins regulating p53 localization.

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Acknowledgements

This work was supported in part by a grant from the European Commission INCO-DEV Program (Contract Grant Number: ICA4-CT-2000-30028).

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Authors and Affiliations

  1. Division of Veterinary Infection Biology and Immunology, Department of Immunology and Cell Biology, Research Center Borstel, Borstel, Germany

    D Haller, M Mackiewicz, S Gerber, D Beyer, B Kullmann, I Schneider, J S Ahmed & U Seitzer

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  1. D Haller
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  2. M Mackiewicz
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  3. S Gerber
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  4. D Beyer
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  6. I Schneider
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  7. J S Ahmed
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  8. U Seitzer
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Correspondence to U Seitzer.

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Haller, D., Mackiewicz, M., Gerber, S. et al. Cytoplasmic sequestration of p53 promotes survival in leukocytes transformed by Theileria. Oncogene 29, 3079–3086 (2010). https://doi.org/10.1038/onc.2010.61

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