PMID- 23872956 OWN - NLM STAT- MEDLINE DCOM- 20140317 LR - 20211203 IS - 1420-9071 (Electronic) IS - 1420-682X (Linking) VI - 71 IP - 4 DP - 2014 Feb TI - The HIF-1 transcription complex is essential for translational control of myeloid hematopoietic cell function by maintaining mTOR phosphorylation. PG - 699-710 LID - 10.1007/s00018-013-1421-2 [doi] AB - 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. FAU - Yasinska, Inna M AU - Yasinska IM AD - Medway School of Pharmacy, University of Kent, Anson Building, Central Avenue, Chatham Maritime, Kent, ME4 4TB, UK. FAU - Gibbs, Bernhard F AU - Gibbs BF FAU - Lall, Gurprit S AU - Lall GS FAU - Sumbayev, Vadim V AU - Sumbayev VV LA - eng PT - Journal Article DEP - 20130720 PL - Switzerland TA - Cell Mol Life Sci JT - Cellular and molecular life sciences : CMLS JID - 9705402 RN - 0 (Hypoxia-Inducible Factor 1) RN - 0 (RNA, Small Interfering) RN - 0 (Tlr2 protein, mouse) RN - 0 (Toll-Like Receptor 2) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) RN - EC 2.7.11.31 (AMP-Activated Protein Kinases) SB - IM MH - AMP-Activated Protein Kinases/metabolism MH - Animals MH - Blood Cells/metabolism MH - Cell Line MH - Enzyme Activation MH - Humans MH - Hypoxia-Inducible Factor 1/genetics/*metabolism MH - Male MH - Mice MH - Myeloid Cells/*metabolism MH - Phosphorylation MH - RNA Interference MH - RNA, Small Interfering/genetics MH - TOR Serine-Threonine Kinases/*metabolism MH - Toll-Like Receptor 2/metabolism EDAT- 2013/07/23 06:00 MHDA- 2014/03/19 06:00 CRDT- 2013/07/23 06:00 PHST- 2013/06/06 00:00 [received] PHST- 2013/07/04 00:00 [accepted] PHST- 2013/07/04 00:00 [revised] PHST- 2013/07/23 06:00 [entrez] PHST- 2013/07/23 06:00 [pubmed] PHST- 2014/03/19 06:00 [medline] AID - 10.1007/s00018-013-1421-2 [doi] PST - ppublish SO - Cell Mol Life Sci. 2014 Feb;71(4):699-710. doi: 10.1007/s00018-013-1421-2. Epub 2013 Jul 20.