Filamin B Serves as a Molecular Scaffold for Type I Interferon-induced c-Jun NH 2 -terminal Kinase Signaling Pathway

• Published in: Molecular biology of the cell 2008-12, Vol.19 (12), p.5116-5130
• Main Authors: Jeon, Young Joo, Choi, Joon Seok, Lee, Jung Yun, Yu, Kyung Ryun, Ka, Seung Hyeun, Cho, Yongcheol, Choi, Eui-Ju, Baek, Sung Hee, Seol, Jae Hong, Park, Dongeun, Bang, Ok Sun, Chung, Chin Ha
• Format: Article
• Language: English
• ISSN: 1059-1524; 1939-4586
• DOI: 10.1091/mbc.e08-06-0576

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 IFNα-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 IFNα-dependent activation of JNK. Furthermore, filamin B promoted IFNα-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.