IRF-2 regulates NF-κB activity by modulating the subcellular localization of NF-κB

Myounghee Chae, Kwangsoo Kim, Sun Mi Park, Ik Soon Jang, Taegun Seo, Dong Min Kim, Il Chul Kim, Je Ho Lee, Junsoo Park

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Nuclear Factor-kappa B (NF-κB) is a transcription factor essential to the control of cell proliferation, survival, differentiation, immune response, and inflammation. Constitutive NF-κB activation has been observed in a broad variety of solid tumors and hematological malignancies, which suggests that NF-κB signaling may perform a critical role in the development of human cancers. Interferon regulatory factor-2 (IRF-2), an antagonistic transcriptional repressor of IRF-1, evidences oncogenic potential, but little is currently known regarding the mechanism underlying the oncogenic activities of IRF-2. In this study, we report that IRF-2 recruits RelA/p65 transcription factors into the nucleus via physical interaction. While the nuclear recruitment of RelA by IRF-2 augments TNFα-induced NF-κB dependent transcription, the N-terminal truncated mutant form of IRF-2 inhibits the nuclear localization of RelA, and thus interferes with NF-κB activation. Furthermore, the knockdown of IRF-2 by IRF-2 siRNA attenuates TNFα-induced NF-κB dependent transcription by inhibiting the nuclear localization of RelA. Thus, these results show that IRF-2 regulates NF-κB activity via the modulation of NF-κB subcellular localization.

Original languageEnglish
Pages (from-to)519-524
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume370
Issue number3
DOIs
Publication statusPublished - 2008 Jun 6

Fingerprint

Interferon Regulatory Factor-2
NF-kappa B
Transcription
Transcription Factor RelA
Chemical activation
Cell proliferation
Human Development
Hematologic Neoplasms
Small Interfering RNA
Tumors
Neoplasms
Cell Survival
Transcription Factors
Cell Proliferation
Modulation

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Chae, Myounghee ; Kim, Kwangsoo ; Park, Sun Mi ; Jang, Ik Soon ; Seo, Taegun ; Kim, Dong Min ; Kim, Il Chul ; Lee, Je Ho ; Park, Junsoo. / IRF-2 regulates NF-κB activity by modulating the subcellular localization of NF-κB. In: Biochemical and Biophysical Research Communications. 2008 ; Vol. 370, No. 3. pp. 519-524.
@article{0c50c8b682564ab2a61baa82b781600e,
title = "IRF-2 regulates NF-κB activity by modulating the subcellular localization of NF-κB",
abstract = "Nuclear Factor-kappa B (NF-κB) is a transcription factor essential to the control of cell proliferation, survival, differentiation, immune response, and inflammation. Constitutive NF-κB activation has been observed in a broad variety of solid tumors and hematological malignancies, which suggests that NF-κB signaling may perform a critical role in the development of human cancers. Interferon regulatory factor-2 (IRF-2), an antagonistic transcriptional repressor of IRF-1, evidences oncogenic potential, but little is currently known regarding the mechanism underlying the oncogenic activities of IRF-2. In this study, we report that IRF-2 recruits RelA/p65 transcription factors into the nucleus via physical interaction. While the nuclear recruitment of RelA by IRF-2 augments TNFα-induced NF-κB dependent transcription, the N-terminal truncated mutant form of IRF-2 inhibits the nuclear localization of RelA, and thus interferes with NF-κB activation. Furthermore, the knockdown of IRF-2 by IRF-2 siRNA attenuates TNFα-induced NF-κB dependent transcription by inhibiting the nuclear localization of RelA. Thus, these results show that IRF-2 regulates NF-κB activity via the modulation of NF-κB subcellular localization.",
author = "Myounghee Chae and Kwangsoo Kim and Park, {Sun Mi} and Jang, {Ik Soon} and Taegun Seo and Kim, {Dong Min} and Kim, {Il Chul} and Lee, {Je Ho} and Junsoo Park",
year = "2008",
month = "6",
day = "6",
doi = "10.1016/j.bbrc.2008.03.136",
language = "English",
volume = "370",
pages = "519--524",
journal = "Biochemical and Biophysical Research Communications",
issn = "0006-291X",
publisher = "Academic Press Inc.",
number = "3",

}

IRF-2 regulates NF-κB activity by modulating the subcellular localization of NF-κB. / Chae, Myounghee; Kim, Kwangsoo; Park, Sun Mi; Jang, Ik Soon; Seo, Taegun; Kim, Dong Min; Kim, Il Chul; Lee, Je Ho; Park, Junsoo.

In: Biochemical and Biophysical Research Communications, Vol. 370, No. 3, 06.06.2008, p. 519-524.

Research output: Contribution to journalArticle

TY - JOUR

T1 - IRF-2 regulates NF-κB activity by modulating the subcellular localization of NF-κB

AU - Chae, Myounghee

AU - Kim, Kwangsoo

AU - Park, Sun Mi

AU - Jang, Ik Soon

AU - Seo, Taegun

AU - Kim, Dong Min

AU - Kim, Il Chul

AU - Lee, Je Ho

AU - Park, Junsoo

PY - 2008/6/6

Y1 - 2008/6/6

N2 - Nuclear Factor-kappa B (NF-κB) is a transcription factor essential to the control of cell proliferation, survival, differentiation, immune response, and inflammation. Constitutive NF-κB activation has been observed in a broad variety of solid tumors and hematological malignancies, which suggests that NF-κB signaling may perform a critical role in the development of human cancers. Interferon regulatory factor-2 (IRF-2), an antagonistic transcriptional repressor of IRF-1, evidences oncogenic potential, but little is currently known regarding the mechanism underlying the oncogenic activities of IRF-2. In this study, we report that IRF-2 recruits RelA/p65 transcription factors into the nucleus via physical interaction. While the nuclear recruitment of RelA by IRF-2 augments TNFα-induced NF-κB dependent transcription, the N-terminal truncated mutant form of IRF-2 inhibits the nuclear localization of RelA, and thus interferes with NF-κB activation. Furthermore, the knockdown of IRF-2 by IRF-2 siRNA attenuates TNFα-induced NF-κB dependent transcription by inhibiting the nuclear localization of RelA. Thus, these results show that IRF-2 regulates NF-κB activity via the modulation of NF-κB subcellular localization.

AB - Nuclear Factor-kappa B (NF-κB) is a transcription factor essential to the control of cell proliferation, survival, differentiation, immune response, and inflammation. Constitutive NF-κB activation has been observed in a broad variety of solid tumors and hematological malignancies, which suggests that NF-κB signaling may perform a critical role in the development of human cancers. Interferon regulatory factor-2 (IRF-2), an antagonistic transcriptional repressor of IRF-1, evidences oncogenic potential, but little is currently known regarding the mechanism underlying the oncogenic activities of IRF-2. In this study, we report that IRF-2 recruits RelA/p65 transcription factors into the nucleus via physical interaction. While the nuclear recruitment of RelA by IRF-2 augments TNFα-induced NF-κB dependent transcription, the N-terminal truncated mutant form of IRF-2 inhibits the nuclear localization of RelA, and thus interferes with NF-κB activation. Furthermore, the knockdown of IRF-2 by IRF-2 siRNA attenuates TNFα-induced NF-κB dependent transcription by inhibiting the nuclear localization of RelA. Thus, these results show that IRF-2 regulates NF-κB activity via the modulation of NF-κB subcellular localization.

UR - http://www.scopus.com/inward/record.url?scp=42749097884&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=42749097884&partnerID=8YFLogxK

U2 - 10.1016/j.bbrc.2008.03.136

DO - 10.1016/j.bbrc.2008.03.136

M3 - Article

C2 - 18395009

AN - SCOPUS:42749097884

VL - 370

SP - 519

EP - 524

JO - Biochemical and Biophysical Research Communications

JF - Biochemical and Biophysical Research Communications

SN - 0006-291X

IS - 3

ER -