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Role of Bax in apoptosis of IL-3-dependent cells

Oncogene volume 20, pages 4476–4483 (2001)Cite this article

Abstract

IL-3 removal was reported to induce membrane association of the apoptotic effector Bax. This report demonstrates that IL-3-dependent cells from Bax-null mice failed to activate caspases after IL-3 removal and survived in an 10-fold lower concentration of IL-3. As IL-3 removal also down-regulates expression of Bcl-X, we examined the relationship between Bcl-X decrease and Bax membrane association. IL-3 removal from BAF-3 cells, followed by sorting caspase-active and caspase-inactive populations, showed that both expressed similar levels of Bcl-X. Inhibition of IL-3 signalling via PI-3 kinase and MEK1/2 resulted in cells with minimal Bcl-X, which remained viable with soluble Bax. However BAF-3-derived cells, which maintained Bcl-X expression without IL-3, also remained viable with soluble Bax on IL-3 removal. Therefore a decrease in Bcl-X is necessary, though not sufficient, for Bax membrane association on IL-3 removal. In contrast, treatment of BAF-3 cells with hydroxyurea induced apoptosis in the absence of a Bcl-X decrease. Furthermore, IL-3-dependent cells from Bax-null mice activated caspases after hydroxyurea treatment and show the same sensitivity to a variety of cytotoxic drugs. Thus, apoptosis after IL-3 removal requires a decrease in Bcl-X and Bax membrane association, whereas that induced by cytotoxic drugs does not.

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Acknowledgements

W Low was the recipient of a Wellcome Trust Travelling Fellowship.

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Authors and Affiliations

  1. Department of Immunology and Molecular Pathology, University College London, Windeyer Institute of Medical Science, 46 Cleveland Street, London, W1P 6DB, UK

    W Low, G Olmos-Centenera, C Madsen & M K L Collins

  2. Immunologie Cellulaire, Laboratoire de Biologie Moleculaire et Cellulaire, Ecole Normale Superieure de Lyon CNRS UMR49 INRA LA 913, 46 allee d'Italie, 69364, Lyon, cedex 07, France

    Y Leverrier

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Correspondence to M K L Collins.

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Low, W., Olmos-Centenera, G., Madsen, C. et al. Role of Bax in apoptosis of IL-3-dependent cells. Oncogene 20, 4476–4483 (2001). https://doi.org/10.1038/sj.onc.1204580

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