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 knockdown-mediated 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.

• Authors: Dongsheng Xu, Florencia Meyer, Erica Ehlers, Laura Blasnitz, Luwen Zhang
• Journal: The Journal of biological chemistry (J Biol Chem) Vol. 286 Issue 20 Pg. 18261-7 (May 20 2011) ISSN: 1083-351X [Electronic] United States
• PMID: 21454650 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: © 2011 by The American Society for Biochemistry and Molecular Biology, Inc.

Chemical References

• IRF5 protein, human
• Interferon Regulatory Factors
• interferon regulatory factor-4

Topics

• B-Lymphocytes (metabolism, pathology, virology)
• Cell Line
• Cell Transformation, Neoplastic (genetics, metabolism, pathology)
• Epstein-Barr Virus Infections (genetics, metabolism, pathology)
• Herpesvirus 4, Human (genetics, metabolism)
• Humans
• Interferon Regulatory Factors (genetics, metabolism)
• Promoter Regions, Genetic (genetics)