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The HIF-1 transcription complex is essential for translational control of myeloid hematopoietic cell function by maintaining mTOR phosphorylation

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Abstract

Mammalian myeloid cells are crucial effectors of host innate immune defense. Normal and pathological responses of these cells require adaptation to signaling stress through the hypoxia-inducible factor 1 (HIF-1) transcription complex. Adapted cells activate the mammalian target of rapamycin (mTOR), via S2448 phosphorylation, which induces de novo translation of vital signaling proteins. However, the molecular mechanisms underlying this signaling dogma remain unclear. Here, we demonstrate for the first time that inactivation of HIF-1, by silencing its inducible alpha subunit, significantly decreases mTOR S2448 phosphorylation caused by ligand-dependent activation of human myeloid leukemia cells. This shows that HIF-1 is essential for the activation of mTOR and serves at a crucial juncture of myeloid cell function in both in vitro and in vivo systems.

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Authors and Affiliations

  1. Medway School of Pharmacy, University of Kent, Anson Building, Central Avenue, Chatham Maritime, Kent, ME4 4TB, UK

    Inna M. Yasinska, Bernhard F. Gibbs, Gurprit S. Lall & Vadim V. Sumbayev

Authors
  1. Inna M. Yasinska
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  2. Bernhard F. Gibbs
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  3. Gurprit S. Lall
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  4. Vadim V. Sumbayev
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Corresponding author

Correspondence to Vadim V. Sumbayev.

Additional information

I. M. Yasinska and B. F. Gibbs contributed equally to this study.

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Yasinska, I.M., Gibbs, B.F., Lall, G.S. et al. The HIF-1 transcription complex is essential for translational control of myeloid hematopoietic cell function by maintaining mTOR phosphorylation. Cell. Mol. Life Sci. 71, 699–710 (2014). https://doi.org/10.1007/s00018-013-1421-2

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  • DOI: https://doi.org/10.1007/s00018-013-1421-2

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