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  • Original Paper
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G1-Cdk activity is required for both proliferation and viability of cytokine-dependent myeloid and erythroid cells

Oncogene volume 20, pages 4198–4208 (2001)Cite this article

Abstract

Hematopoietic cytokines are critically required for survival and cell proliferation of myeloid and erythroid progenitors. It is poorly understood how the apoptotic machinery of progenitor cells senses the absence of specific cytokines. Here we show that G1-Cdk activity is essential for cytokine-mediated viability of myeloid and erythroid progenitors. Cytokine deprivation is associated with rapid downregulation of G1-Cdk activity, cell cycle arrest, and apoptosis. Specific inhibition of G1-Cdk activity results in apoptotic cell death in the presence of saturating cytokine levels. In contrast, specific cell cycle arrest in G2/M does not affect viability. When cell proliferation is arrested by cytokine withdrawal, primary erythroid progenitors expressing v-ErbA maintain G1-Cdk activity and undergo delayed apoptosis. Cdk-inhibitors strongly enhance apoptosis in starved v-ErbA cells, indicating that sustained Cdk activity is required for protection from apoptosis by v-ErbA.

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Acknowledgements

We thank Dr Adi Himmler, Boehringer Ingelheim, Vienna, for FDCP-1 cells and FDCP-1/Bcl2 cells. We are grateful to Dr Laurent Meijer for the kind gift of roscovitine. In addition, we are indebted to Dr Meinrad Busslinger and Dr R Moriggl for helpful comments on the manuscript.

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Authors and Affiliations

  1. Research Institute of Molecular Pathology, Dr. Bohr Gasse 7, Vienna, A-1030, Austria

    Johannes FX Hofmann, Martina Sykora & Hartmut Beug

  2. Boehringer Ingelheim, A Onkologische Forschung, Birkendorfer Str. 65, D-88400 Biberach a.d., Riss, Germany

    Norbert Redemann

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  1. Johannes FX Hofmann
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  2. Martina Sykora
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  4. Hartmut Beug
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Correspondence to Hartmut Beug.

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Hofmann, J., Sykora, M., Redemann, N. et al. G1-Cdk activity is required for both proliferation and viability of cytokine-dependent myeloid and erythroid cells. Oncogene 20, 4198–4208 (2001). https://doi.org/10.1038/sj.onc.1204550

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