Interferon Regulatory Factor 4 (IRF-4) targets IRF-5 to regulate Epstein-Barr virus transformation

Dongsheng Xu, Florencia Meyer, Erica Ehlers, Laura Blasnitz, Luwen Zhang

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

The cellular interferon regulatory factor-4 (IRF-4), which is a member of IRF family, is involved in the development of multiple myeloma and Epstein-Barr virus (EBV)-mediated transformation of B lymphocytes. However, the molecular mechanism of IRF-4 in cellular transformation is unknown. We have found that knockdown of IRF-4 leads to high expression of IRF-5, a pro-apoptotic member in the IRF family. Overexpression of IRF-4 represses IRF-5 expression. Reduction of IRF-4 leads to growth inhibition, and the restoration of IRF-4 by exogenous plasmids correlates with the growth recovery and reduces IRF-5 expression. In addition, IRF-4 negatively regulates IRF-5 promoter reporter activities and binds to IRF-5 promoters in vivo and in vitro. Knockdown of IRF-5 rescues IRF-4 knockdownmediated growth inhibition, and IRF-5 overexpression alone is sufficient to induce cellular growth inhibition of EBV-transformed cells. Therefore, IRF-5 is one of the targets of IRF-4, and IRF-4 regulates the growth of EBV-transformed cells partially through IRF-5. This work provides insight on how IRFs interact with one another to participate in viral pathogenesis and transformation.

Original languageEnglish (US)
Pages (from-to)18261-18267
Number of pages7
JournalJournal of Biological Chemistry
Volume286
Issue number20
DOIs
StatePublished - May 20 2011

Fingerprint

Human Herpesvirus 4
Viruses
Growth
interferon regulatory factor-4
Lymphocytes
Multiple Myeloma
Restoration
Plasmids
B-Lymphocytes
Recovery

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Interferon Regulatory Factor 4 (IRF-4) targets IRF-5 to regulate Epstein-Barr virus transformation. / Xu, Dongsheng; Meyer, Florencia; Ehlers, Erica; Blasnitz, Laura; Zhang, Luwen.

In: Journal of Biological Chemistry, Vol. 286, No. 20, 20.05.2011, p. 18261-18267.

Research output: Contribution to journalArticle

Xu, Dongsheng ; Meyer, Florencia ; Ehlers, Erica ; Blasnitz, Laura ; Zhang, Luwen. / Interferon Regulatory Factor 4 (IRF-4) targets IRF-5 to regulate Epstein-Barr virus transformation. In: Journal of Biological Chemistry. 2011 ; Vol. 286, No. 20. pp. 18261-18267.
@article{d2aa5cdbe3c94d519fa094bc524f9133,
title = "Interferon Regulatory Factor 4 (IRF-4) targets IRF-5 to regulate Epstein-Barr virus transformation",
abstract = "The cellular interferon regulatory factor-4 (IRF-4), which is a member of IRF family, is involved in the development of multiple myeloma and Epstein-Barr virus (EBV)-mediated transformation of B lymphocytes. However, the molecular mechanism of IRF-4 in cellular transformation is unknown. We have found that knockdown of IRF-4 leads to high expression of IRF-5, a pro-apoptotic member in the IRF family. Overexpression of IRF-4 represses IRF-5 expression. Reduction of IRF-4 leads to growth inhibition, and the restoration of IRF-4 by exogenous plasmids correlates with the growth recovery and reduces IRF-5 expression. In addition, IRF-4 negatively regulates IRF-5 promoter reporter activities and binds to IRF-5 promoters in vivo and in vitro. Knockdown of IRF-5 rescues IRF-4 knockdownmediated growth inhibition, and IRF-5 overexpression alone is sufficient to induce cellular growth inhibition of EBV-transformed cells. Therefore, IRF-5 is one of the targets of IRF-4, and IRF-4 regulates the growth of EBV-transformed cells partially through IRF-5. This work provides insight on how IRFs interact with one another to participate in viral pathogenesis and transformation.",
author = "Dongsheng Xu and Florencia Meyer and Erica Ehlers and Laura Blasnitz and Luwen Zhang",
year = "2011",
month = "5",
day = "20",
doi = "10.1074/jbc.M110.210542",
language = "English (US)",
volume = "286",
pages = "18261--18267",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "20",

}

TY - JOUR

T1 - Interferon Regulatory Factor 4 (IRF-4) targets IRF-5 to regulate Epstein-Barr virus transformation

AU - Xu, Dongsheng

AU - Meyer, Florencia

AU - Ehlers, Erica

AU - Blasnitz, Laura

AU - Zhang, Luwen

PY - 2011/5/20

Y1 - 2011/5/20

N2 - The cellular interferon regulatory factor-4 (IRF-4), which is a member of IRF family, is involved in the development of multiple myeloma and Epstein-Barr virus (EBV)-mediated transformation of B lymphocytes. However, the molecular mechanism of IRF-4 in cellular transformation is unknown. We have found that knockdown of IRF-4 leads to high expression of IRF-5, a pro-apoptotic member in the IRF family. Overexpression of IRF-4 represses IRF-5 expression. Reduction of IRF-4 leads to growth inhibition, and the restoration of IRF-4 by exogenous plasmids correlates with the growth recovery and reduces IRF-5 expression. In addition, IRF-4 negatively regulates IRF-5 promoter reporter activities and binds to IRF-5 promoters in vivo and in vitro. Knockdown of IRF-5 rescues IRF-4 knockdownmediated growth inhibition, and IRF-5 overexpression alone is sufficient to induce cellular growth inhibition of EBV-transformed cells. Therefore, IRF-5 is one of the targets of IRF-4, and IRF-4 regulates the growth of EBV-transformed cells partially through IRF-5. This work provides insight on how IRFs interact with one another to participate in viral pathogenesis and transformation.

AB - The cellular interferon regulatory factor-4 (IRF-4), which is a member of IRF family, is involved in the development of multiple myeloma and Epstein-Barr virus (EBV)-mediated transformation of B lymphocytes. However, the molecular mechanism of IRF-4 in cellular transformation is unknown. We have found that knockdown of IRF-4 leads to high expression of IRF-5, a pro-apoptotic member in the IRF family. Overexpression of IRF-4 represses IRF-5 expression. Reduction of IRF-4 leads to growth inhibition, and the restoration of IRF-4 by exogenous plasmids correlates with the growth recovery and reduces IRF-5 expression. In addition, IRF-4 negatively regulates IRF-5 promoter reporter activities and binds to IRF-5 promoters in vivo and in vitro. Knockdown of IRF-5 rescues IRF-4 knockdownmediated growth inhibition, and IRF-5 overexpression alone is sufficient to induce cellular growth inhibition of EBV-transformed cells. Therefore, IRF-5 is one of the targets of IRF-4, and IRF-4 regulates the growth of EBV-transformed cells partially through IRF-5. This work provides insight on how IRFs interact with one another to participate in viral pathogenesis and transformation.

UR - http://www.scopus.com/inward/record.url?scp=79955969946&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79955969946&partnerID=8YFLogxK

U2 - 10.1074/jbc.M110.210542

DO - 10.1074/jbc.M110.210542

M3 - Article

C2 - 21454650

AN - SCOPUS:79955969946

VL - 286

SP - 18261

EP - 18267

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 20

ER -