title: IκBζ, an atypical member of the inhibitor of nuclear factor kappa B family, is induced by γ-irradiation in glioma cells, regulating cytokine secretion and associated with poor prognosis.
abstract: The inhibitor of nuclear factor kappa B zeta (IκBζ) is an atypical member of the IκB protein family. Its function in regulating the activity of the transcription factor nuclear factor kappa B (NFκB) as well as its involvement in cancer-associated processes is poorly understood. In glioma patients, enhanced expression of IκBζ in tumor specimen is associated with poor prognosis. Here we report that IκBζ is upregulated in a glioma cell line resistant towards NFκB-dependent non-apoptotic cell death. Upon γ-irradiation of glioma cells, IκBζ expression is enhanced, and subsequently serves as a transcriptional activator of the tumor promoting cytokines interleukin (IL-6), IL-8 and chemokine (C-X-C motif) ligand 1 (CXCL1) that are known to be involved in glioma associated inflammatory processes. In contrast, shRNA-mediated knockdown of IκBζ reduces the expression of the aforementioned cytokines. We propose a previously unappreciated role of IκBζ in the inflammatory micromilieu as well as progression in glioma.
authors.affiliation: Hertie Institute for Clinical Brain Research and Center Neurology, Molecular Neurology, Karl Eberhards University of Tübingen, Tübingen, Germany.
authors.forename: Heiko
authors.initials: H
authors.lastname: Brennenstuhl
authors.affiliation: Hertie Institute for Clinical Brain Research and Center Neurology, Molecular Neurology, Karl Eberhards University of Tübingen, Tübingen, Germany.
authors.forename: Angela
authors.initials: A
authors.lastname: Armento
authors.affiliation: Edinger Institute (Neurological Institute), Goethe University, Frankfurt am Main, Germany.
authors.forename: Anne Kristin
authors.initials: AK
authors.lastname: Braczysnki
authors.affiliation: Edinger Institute (Neurological Institute), Goethe University, Frankfurt am Main, Germany.
authors.forename: Michel
authors.initials: M
authors.lastname: Mittelbronn
authors.affiliation: Hertie Institute for Clinical Brain Research and Center Neurology, Molecular Neurology, Karl Eberhards University of Tübingen, Tübingen, Germany.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Naumann
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D063646:Carcinogenesis / Q000235:genetics*; D016923:Cell Death / Q000528:radiation effects; D045744:Cell Line, Tumor; D054360:Chemokine CXCL1 / Q000096:biosynthesis; D005720:Gamma Rays; D015972:Gene Expression Regulation, Neoplastic / Q000528:radiation effects; D005910:Glioma / Q000235:genetics*; D006801:Humans; D020672:I-kappa B Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D015850:Interleukin-6 / Q000096:biosynthesis; D016209:Interleukin-8 / Q000096:biosynthesis; D016328:NF-kappa B / Q000096:biosynthesis / Q000235:genetics*; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D011379:Prognosis; D034741:RNA, Small Interfering
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C475829:CXCL1 protein, human; D054360:Chemokine CXCL1; D020672:I-kappa B Proteins; D015850:Interleukin-6; D016209:Interleukin-8; D016328:NF-kappa B; C417234:NFKBIZ protein, human; D009687:Nuclear Proteins; D034741:RNA, Small Interfering