Original Article

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

Correspondence to: Steve Gerondakis, The Walter and Eliza Hall Institute of Medical Research, Post Office, The Royal Melbourne Hospital, Parkville, Victoria 3050, Australia. Tel:61-39-345-2542 Fax:61-39-347-0852 E-mail: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 B can repress the transcription of IFN-regulated genes in a cell type–specific manner.

Key Words: Rel/NF-B, lymphocytes, IRF-4, interferon, transcription

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