Filamin B serves as a molecular scaffold for type I interferon-induced c-Jun NH2-terminal kinase signaling pathway

Joo Jeon Young, Seok Choi Joon, Yun Lee Jung, Ryun Yu Kyung, Hyeun Ka Seung, Yongcheol Cho, Eui Ju Choi, Hee Baek Sung, Hong Seol Jae, Dongeun Park, Sun Bang Ok, Ha Chung Chin

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29 Citations (Scopus)

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 NH2-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.

Original languageEnglish
Pages (from-to)5116-5130
Number of pages15
JournalMolecular Biology of the Cell
Volume19
Issue number12
DOIs
Publication statusPublished - 2008 Dec

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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    Young, J. J., Joon, S. C., Jung, Y. L., Kyung, R. Y., Seung, H. K., Cho, Y., Choi, E. J., Sung, H. B., Jae, H. S., Park, D., Ok, S. B., & Chin, H. C. (2008). Filamin B serves as a molecular scaffold for type I interferon-induced c-Jun NH2-terminal kinase signaling pathway. Molecular Biology of the Cell, 19(12), 5116-5130. https://doi.org/10.1091/mbc.E08-06-0576