|
|
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result sql = Filamin B serves as a molecular scaffold for type I interferon-induced c-Jun NH2-terminal kinase signaling pathway.
Filamin B serves as a molecular scaffold for type I interferon-induced c-Jun NH2-terminal kinase signaling pathway.char = T;code = 84
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char = s;code = 115
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char = e;code = 101
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result sql = 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.
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char = e;code = 101
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char = s;code = 115
char = ;code = 32
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char = a;code = 97
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result sql = Filamin B serves as a molecular scaffold for type I interferon-induced c-Jun NH2-terminal kinase signaling pathway.
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result sql = 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.
Publication: Mol. Biol. Cell 2008 Dec ;19(12)::5116-30. :doi: 10.1091/mbc.E08-06-0576.
Publication Date: 2008 Dec
Study Author(s): 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;
Institution: School of Biological Sciences, Seoul National University, Seoul 151-742, Korea.
Shortcut link to this study:
Publication Date: 2008 Dec
Study Author(s): 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;
Institution: School of Biological Sciences, Seoul National University, Seoul 151-742, Korea.
Shortcut link to this study:
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.
PMID: 18815275
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