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

Research output: Contribution to journalArticle

28 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 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.

Original languageEnglish
Pages (from-to)5116-5130
Number of pages15
JournalMolecular Biology of the Cell
Volume19
Issue number12
DOIs
Publication statusPublished - 2008 Dec 1

Fingerprint

Filamins
Interferon Type I
JNK Mitogen-Activated Protein Kinases
Phosphotransferases
Interferons
MAP Kinase Kinase Kinase 4
Antiviral Agents
MAP Kinase Kinase Kinase 1
Apoptosis
Janus Kinases
MAP Kinase Kinase Kinases
Transducers
Protein-Tyrosine Kinases
Small Interfering RNA
Melanoma

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Filamin B serves as a molecular scaffold for type I interferon-induced c-Jun NH2-terminal kinase signaling pathway. / Young, Joo Jeon; Joon, Seok Choi; Jung, Yun Lee; Kyung, Ryun Yu; Seung, Hyeun Ka; Cho, Yongcheol; Choi, Eui Ju; Sung, Hee Baek; Jae, Hong Seol; Park, Dongeun; Ok, Sun Bang; Chin, Ha Chung.

In: Molecular Biology of the Cell, Vol. 19, No. 12, 01.12.2008, p. 5116-5130.

Research output: Contribution to journalArticle

Young, JJ, Joon, SC, Jung, YL, Kyung, RY, Seung, HK, Cho, Y, Choi, EJ, Sung, HB, Jae, HS, Park, D, Ok, SB & Chin, HC 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, vol. 19, no. 12, pp. 5116-5130. https://doi.org/10.1091/mbc.E08-06-0576
Young, Joo Jeon ; Joon, Seok Choi ; Jung, Yun Lee ; Kyung, Ryun Yu ; Seung, Hyeun Ka ; Cho, Yongcheol ; Choi, Eui Ju ; Sung, Hee Baek ; Jae, Hong Seol ; Park, Dongeun ; Ok, Sun Bang ; Chin, Ha Chung. / Filamin B serves as a molecular scaffold for type I interferon-induced c-Jun NH2-terminal kinase signaling pathway. In: Molecular Biology of the Cell. 2008 ; Vol. 19, No. 12. pp. 5116-5130.
@article{7992a903082d4d7d917daa9af2f08f46,
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 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.",
author = "Young, {Joo Jeon} and Joon, {Seok Choi} and Jung, {Yun Lee} and Kyung, {Ryun Yu} and Seung, {Hyeun Ka} and Yongcheol Cho and Choi, {Eui Ju} and Sung, {Hee Baek} and Jae, {Hong Seol} and Dongeun Park and Ok, {Sun Bang} and Chin, {Ha Chung}",
year = "2008",
month = "12",
day = "1",
doi = "10.1091/mbc.E08-06-0576",
language = "English",
volume = "19",
pages = "5116--5130",
journal = "Molecular Biology of the Cell",
issn = "1059-1524",
publisher = "American Society for Cell Biology",
number = "12",

}

TY - JOUR

T1 - Filamin B serves as a molecular scaffold for type I interferon-induced c-Jun NH2-terminal kinase signaling pathway

AU - Young, Joo Jeon

AU - Joon, Seok Choi

AU - Jung, Yun Lee

AU - Kyung, Ryun Yu

AU - Seung, Hyeun Ka

AU - Cho, Yongcheol

AU - Choi, Eui Ju

AU - Sung, Hee Baek

AU - Jae, Hong Seol

AU - Park, Dongeun

AU - Ok, Sun Bang

AU - Chin, Ha Chung

PY - 2008/12/1

Y1 - 2008/12/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=59449085097&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=59449085097&partnerID=8YFLogxK

U2 - 10.1091/mbc.E08-06-0576

DO - 10.1091/mbc.E08-06-0576

M3 - Article

C2 - 18815275

AN - SCOPUS:59449085097

VL - 19

SP - 5116

EP - 5130

JO - Molecular Biology of the Cell

JF - Molecular Biology of the Cell

SN - 1059-1524

IS - 12

ER -