Literature DB >> 10215868

NFkappaB activation is required for interferon regulatory factor-1-mediated interferon beta induction.

S Kirchhoff1, D Wilhelm, P Angel, H Hauser.   

Abstract

The interferon regulatory factor 1 (IRF-1) acts as a transcriptional inducer of the interferon beta (IFN-beta) gene and interferon-stimulated genes. Here we report that IRF-1-mediated IFN-beta induction depends on NFkappaB activity. IRF-1 by itself initiates NFkappaB activation by inducing a reduction in cellular MAD3/IkappaBalpha, an inhibitor of NFkappaB. After nuclear translocation, NFkappaB synergizes with IRF-1 on the cis-elements positive regulatory domain (PRD)II and PRDI/III to induce transcription of the IFN-beta gene. In contrast with IFN-beta transcription induced by dsRNA or virus, c-Jun/ATF-2 binding to PRDIV is not involved. Recombinant MAD3/IkappaBalpha is phosphorylated in vitro by extracts from IRF-1-expressing cells. IRF-1-dependent MAD3/IkappaBalpha degradation is not detectable in cells expressing a dominant negative mutant of the protein kinase PKR, suggesting that PKR mediates MAD3/IkappaBalpha degradation.

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Year:  1999        PMID： 10215868     DOI： 10.1046/j.1432-1327.1999.00308.x

Source DB:  PubMed          Journal:  Eur J Biochem        ISSN： 0014-2956


  7 in total

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  7 in total

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