title: The HIF-1 transcription complex is essential for translational control of myeloid hematopoietic cell function by maintaining mTOR phosphorylation.
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.
authors.affiliation: Medway School of Pharmacy, University of Kent, Anson Building, Central Avenue, Chatham Maritime, Kent, ME4 4TB, UK.
authors.forename: Inna M
authors.initials: IM
authors.lastname: Yasinska
authors.forename: Bernhard F
authors.initials: BF
authors.lastname: Gibbs
authors.forename: Gurprit S
authors.initials: GS
authors.lastname: Lall
authors.forename: Vadim V
authors.initials: VV
authors.lastname: Sumbayev
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000818:Animals; D001773:Blood Cells / Q000378:metabolism; D002460:Cell Line; D004789:Enzyme Activation; D006801:Humans; D051793:Hypoxia-Inducible Factor 1 / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D022423:Myeloid Cells / Q000378:metabolism*; D010766:Phosphorylation; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D051195:Toll-Like Receptor 2 / Q000378:metabolism
chemical_list: D051793:Hypoxia-Inducible Factor 1; D034741:RNA, Small Interfering; C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2; D058570:TOR Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases