title: Optineurin with amyotrophic lateral sclerosis-related mutations abrogates inhibition of interferon regulatory factor-3 activation.
abstract: Optineurin has been shown to be involved in primary open-angle glaucoma. We recently found that optineurin is involved in familial amyotrophic lateral sclerosis (ALS). On the other hand, optineurin has been shown to inhibit transcription factors related to innate immunity such as NF-κB and interferon regulatory factor-3 (IRF3). In the present study, the effect of ALS-associated optineurin mutations on IRF3 activation was investigated. Optineurin inhibited IRF3 activation induced by melanoma differentiation-associated gene 5 or Toll-IL-1 receptor domain-containing adaptor-inducing interferon-β. The inhibition was abrogated by mutations related to ALS but not by a mutation related to glaucoma. Reporter assay indicated that the JAK-STAT signaling pathway was not affected by optineurin. These results show that ALS-related optineurin is involved in the IRF3 activation pathway. Pathogenesis of ALS may be associated with some kind of innate immunity, especially that against virus infection, through IRF3 activation.
authors: Department of Virology, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan. tsaka@hiroshima-u.ac.jp
authors: Takemasa
authors: T
authors: Sakaguchi
authors: Takashi
authors: T
authors: Irie
authors: Ryoko
authors: R
authors: Kawabata
authors: Asuka
authors: A
authors: Yoshida
authors: Hirofumi
authors: H
authors: Maruyama
authors: Hideshi
authors: H
authors: Kawakami
mesh_terms: D018797:Cell Cycle Proteins; D002461:Cell Line, Transformed; D053487:DEAD-box RNA Helicases / Q000235:genetics / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism / Q000502:physiology; D005786:Gene Expression Regulation / Q000235:genetics*; D049452:Green Fluorescent Proteins / Q000235:genetics; D006801:Humans; D050838:Interferon Regulatory Factor-3 / Q000235:genetics / Q000378:metabolism*; D000072640:Interferon-Induced Helicase, IFIH1; D026901:Membrane Transport Proteins; D008954:Models, Biological; D009154:Mutation / Q000235:genetics*; D035582:Transcription Factor TFIIIA / Q000235:genetics*; D014162:Transfection / Q000379:methods
chemical_list: D018797:Cell Cycle Proteins; D050838:Interferon Regulatory Factor-3; D026901:Membrane Transport Proteins; C409460:OPTN protein, human; D035582:Transcription Factor TFIIIA; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; C452815:IFIH1 protein, human; D053487:DEAD-box RNA Helicases; D000072640:Interferon-Induced Helicase, IFIH1