The Journal of Experimental Medicine
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Published online 17 April 2000.
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© The Rockefeller University Press, 0022-1007/2000/4/1281/ $5.00
The Journal of Experimental Medicine, Volume 191, Number 8, April 17, 2000 1281-1292


Original Article

Rel Induces Interferon Regulatory Factor 4 (IRF-4) Expression in Lymphocytes: Modulation of Interferon-Regulated Gene Expression by Rel/Nuclear Factor {kappa}B



Raelene J. Grumonta and Steve Gerondakisa

a Walter and Eliza Hall Institute of Medical Research, The Royal Melbourne Hospital, Parkville, Victoria 3050, Australia
The Walter and Eliza Hall Institute of Medical Research, Post Office, The Royal Melbourne Hospital, Parkville, Victoria 3050, Australia.61-39-347-085261-39-345-2542

gerondakis{at}wehi.edu.au

In lymphocytes, the Rel transcription factor is essential in establishing a pattern of gene expression that promotes cell proliferation, survival, and differentiation. Here we show that mitogen-induced expression of interferon (IFN) regulatory factor 4 (IRF-4), a lymphoid-specific member of the IFN family of transcription factors, is Rel dependent. Consistent with IRF-4 functioning as a repressor of IFN-induced gene expression, the absence of IRF-4 expression in c-rel–/– B cells coincided with a greater sensitivity of these cells to the antiproliferative activity of IFNs. In turn, enforced expression of an IRF-4 transgene restored IFN modulated c-rel–/– B cell proliferation to that of wild-type cells. This cross-regulation between two different signaling pathways represents a novel mechanism that Rel/nuclear factor {kappa}B can repress the transcription of IFN-regulated genes in a cell type–specific manner.

Key Words: Rel/NF-{kappa}B • lymphocytes • IRF-4 • interferon • transcription


Abbreviations used in this paper: CAT, chloramphenicol acetyltransferase; GAPDH, glyceraldehyde 3-phosphate dehydrogenase; GFP, green fluorescent protein; IRF, IFN regulatory factor; ISRE, IFN stimulation response element; NF, nuclear factor; OAS, oligoadenylate synthetase; RHD, Rel homology domain; RP, radioprotective.

© 2000 The Rockefeller University Press


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