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Molecular and Cellular Biology, June 2002, p. 3942-3957, Vol. 22, No. 11
0270-7306/02/$04.00+0     DOI: 10.1128/MCB.22.11.3942-3957.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

A Novel Interferon Regulatory Factor (IRF), IRF-10, Has a Unique Role in Immune Defense and Is Induced by the v-Rel Oncoprotein

Jirí Nehyba,1 Radmila Hrdlicková,1 Joan Burnside,2 and Henry R. Bose, Jr.1*

Section of Molecular Genetics and Microbiology and Institute for Cellular and Molecular Biology, University of Texas at Austin, Austin, Texas 78712-1095,1 Delaware Biotechnology Institute, Newark, Delaware 197112

Received 23 October 2001/ Returned for modification 11 December 2001/ Accepted 19 February 2002

The cloning and functional characterization of a novel interferon regulatory factor (IRF), IRF-10, are described. IRF-10 is most closely related to IRF-4 but differs in both its constitutive and inducible expression. The expression of IRF-10 is inducible by interferons (IFNs) and by concanavalin A. In contrast to that of other IRFs, the inducible expression of IRF-10 is characterized by delayed kinetics and requires protein synthesis, suggesting a unique role in the later stages of an antiviral defense. Accordingly, IRF-10 is involved in the upregulation of two primary IFN-{gamma} target genes (major histocompatibility complex [MHC] class I and guanylate-binding protein) and interferes with the induction of the type I IFN target gene for 2',5'-oligo(A) synthetase. IRF-10 binds the interferon-stimulated response element site of the MHC class I promoter. In contrast to that of IRF-1, which has some of the same functional characteristics, the expression of IRF-10 is not cytotoxic for fibroblasts or B cells. The expression of IRF-10 is induced by the oncogene v-rel, the proto-oncogene c-rel, and IRF-4 in a tissue-specific manner. Moreover, v-Rel and IRF-4 synergistically cooperate in the induction of IRF-10 in fibroblasts. The level of IRF-10 induction in lymphoid cell lines by Rel proteins correlates with Rel transformation potential. These results suggest that IRF-10 plays a role in the late stages of an immune defense by regulating the expression some of the IFN-{gamma} target genes in the absence of a cytotoxic effect. Furthermore, IRF-10 expression is regulated, at least in part, by members of the Rel/NF-{kappa}B and IRF families.

* Corresponding author. Mailing address: Section of Molecular Genetics and Microbiology, The University of Texas at Austin, Austin, TX 78712-1095. Phone: (512) 471-5525. Fax: (512) 471-2130. E-mail: bose{at}mail.utexas.edu.

Molecular and Cellular Biology, June 2002, p. 3942-3957, Vol. 22, No. 11
0022-538X/02/$04.00+0     DOI: 10.1128/MCB.22.11.3942-3957.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

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