title: Filamin B serves as a molecular scaffold for type I interferon-induced c-Jun NH2-terminal kinase signaling pathway.
abstract: Type I interferons (IFNs) activate Janus tyrosine kinase-signal transducer and activator of transcription pathway for exerting pleiotropic biological effects, including antiviral, antiproliferative, and immunomodulatory responses. Here, we demonstrate that filamin B functions as a scaffold that links between activated Rac1 and a c-Jun NH(2)-terminal kinase (JNK) cascade module for mediating type I IFN signaling. Filamin B interacted with Rac1, mitogen-activated protein kinase kinase kinase 1, mitogen-activated protein kinase kinase 4, and JNK. Filamin B markedly enhanced IFNalpha-dependent Rac1 activation and the sequential activation of the JNK cascade members. Complementation assays using M2 melanoma cells revealed that filamin B, but not filamin A, is required for IFNalpha-dependent activation of JNK. Furthermore, filamin B promoted IFNalpha-induced apoptosis, whereas short hairpin RNA-mediated knockdown of filamin B prevented it. These results establish a novel function of filamin B as a molecular scaffold in the JNK signaling pathway for type I IFN-induced apoptosis, thus providing the biological basis for antitumor and antiviral functions of type I IFNs.
authors.affiliation: School of Biological Sciences, Seoul National University, Seoul 151-742, Korea.
authors.forename: Young Joo
authors.initials: YJ
authors.lastname: Jeon
authors.forename: Joon Seok
authors.initials: JS
authors.lastname: Choi
authors.forename: Jung Yun
authors.initials: JY
authors.lastname: Lee
authors.forename: Kyung Ryun
authors.initials: KR
authors.lastname: Yu
authors.forename: Seung Hyeun
authors.initials: SH
authors.lastname: Ka
authors.forename: Yongcheol
authors.initials: Y
authors.lastname: Cho
authors.forename: Eui-Ju
authors.initials: EJ
authors.lastname: Choi
authors.forename: Sung Hee
authors.initials: SH
authors.lastname: Baek
authors.forename: Jae Hong
authors.initials: JH
authors.lastname: Seol
authors.forename: Dongeun
authors.initials: D
authors.lastname: Park
authors.forename: Ok Sun
authors.initials: OS
authors.lastname: Bang
authors.forename: Chin Ha
authors.initials: CH
authors.lastname: Chung
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D022081:Cell Surface Extensions / Q000378:metabolism; D003285:Contractile Proteins / Q000235:genetics / Q000378:metabolism*; D004789:Enzyme Activation; D064448:Filamins; D006367:HeLa Cells; D006801:Humans; D007370:Interferon Type I / Q000235:genetics / Q000378:metabolism*; D048031:JNK Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000502:physiology*; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D025941:Protein Interaction Mapping; D034622:RNA Interference; D020830:rac1 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D003285:Contractile Proteins; D064448:Filamins; D007370:Interferon Type I; D008840:Microfilament Proteins; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D020830:rac1 GTP-Binding Protein