title: Inhibitor of kappaB kinase is required to activate a subset of interferon gamma-stimulated genes.
abstract: IkappaB kinase (IKK), discovered as the major activator of NF-kappaB, plays additional roles in signaling. By using mouse embryo fibroblasts (MEFs) lacking both the alpha and beta subunits of IKK, we find that these proteins are required for induction of a major subset of IFNgamma-stimulated genes and that this requirement is independent of NF-kappaB activation. Furthermore, there is no defect in IFNgamma-stimulated signal transducer and activator of transcription 1 (Stat1) activation or function in the IKKalpha/beta-null MEFs. Therefore, although activated Stat1 dimers are necessary for the activation of these genes in response to IFNgamma, they are not sufficient. These results reveal an important additional pathway for IFNgamma-stimulated gene expression in which an NF-kappaB-independent function of IKK is required.
authors.affiliation: Departments of Cancer Biology, Neurosciences, and Molecular Biology, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA.
authors.forename: Nywana
authors.initials: N
authors.lastname: Sizemore
authors.forename: Anju
authors.initials: A
authors.lastname: Agarwal
authors.forename: Kingshuk
authors.initials: K
authors.lastname: Das
authors.forename: Natalia
authors.initials: N
authors.lastname: Lerner
authors.forename: Michael
authors.initials: M
authors.lastname: Sulak
authors.forename: Sandhya
authors.initials: S
authors.lastname: Rani
authors.forename: Richard
authors.initials: R
authors.lastname: Ransohoff
authors.forename: David
authors.initials: D
authors.lastname: Shultz
authors.forename: George R
authors.initials: GR
authors.lastname: Stark
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism; D019281:Dimerization; D005347:Fibroblasts; D017353:Gene Deletion; D005786:Gene Expression Regulation / Q000187:drug effects*; D051550:I-kappa B Kinase; D007371:Interferon-gamma / Q000494:pharmacology*; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D020836:Protein Structure, Quaternary; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D050794:STAT1 Transcription Factor; D015534:Trans-Activators / Q000737:chemistry / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D004268:DNA-Binding Proteins; D016328:NF-kappa B; D012333:RNA, Messenger; D050794:STAT1 Transcription Factor; C494080:Stat1 protein, mouse; D015534:Trans-Activators; D007371:Interferon-gamma; D017346:Protein Serine-Threonine Kinases; C496564:Chuk protein, mouse; D051550:I-kappa B Kinase; C496562:Ikbkb protein, mouse; C496566:Ikbke protein, mouse