In:
Molecular Biology of the Cell, American Society for Cell Biology (ASCB), Vol. 19, No. 12 ( 2008-12), p. 5116-5130
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 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.
Type of Medium:
Online Resource
ISSN:
1059-1524
,
1939-4586
DOI:
10.1091/mbc.e08-06-0576
Language:
English
Publisher:
American Society for Cell Biology (ASCB)
Publication Date:
2008
detail.hit.zdb_id:
1474922-1
SSG:
12
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