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

Yasinska, Inna M, Gibbs, Bernhard F, Lall, Gurprit S., Sumbayev, Vadim V. (2014) The HIF-1 transcription complex is essential for translational control of myeloid hematopoietic cell function by maintaining mTOR phosphorylation. Cellular and molecular life sciences : CMLS, 71 (4). pp. 699-710. ISSN 1420-9071. (doi:10.1007/s00018-013-1421-2) (Access to this publication is currently restricted. You may be able to access a copy if URLs are provided) (KAR id:44736)

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http://dx.doi.org/10.1007/s00018-013-1421-2

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.

Item Type: Article
DOI/Identification number: 10.1007/s00018-013-1421-2
Uncontrolled keywords: Myeloid cells Inflammation, HIF-1 transcription complex, mTOR (mammalian target of rapamycin)
Subjects: R Medicine
Divisions: Faculties > Sciences > Medway School of Pharmacy
Depositing User: Gurprit Lall
Date Deposited: 17 Nov 2014 15:53 UTC
Last Modified: 11 Feb 2020 14:05 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/44736 (The current URI for this page, for reference purposes)
Lall, Gurprit S.: https://orcid.org/0000-0003-3725-4795
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