Inhibitor of kappaB kinase is required to activate a subset of interferon gamma-stimulated genes.
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.
Sizemore
Nywana
N
Departments of Cancer Biology, Neurosciences, and Molecular Biology, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA.
Agarwal
Anju
A
Das
Kingshuk
K
Lerner
Natalia
N
Sulak
Michael
M
Rani
Sandhya
S
Ransohoff
Richard
R
Shultz
David
D
Stark
George R
GR
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
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