TRIF [TIR (Toll/interleukin-1 receptor) domain-containing adaptor protein inducing interferon β; also known as TICAM-1 (TIR-containing adaptor molecule-1)] is a key adaptor for TLR3 (Toll-like receptor 3)- and TLR4-mediated signalling. We have performed a detailed annotation of the human TRIF gene and fine analysis of the basal and inducible promoter elements lying 5´ to the site of initiation of transcription. Human TRIF maps to chromosome 19p13.3 and is flanked upstream by TIP47, which encodes the mannose 6-phosphate receptor binding protein, and downstream by a gene encoding FEM1a, a human homologue of the Caenorhabditis elegans Feminisation-1 gene. Using promoter–reporter deletion constructs, we identified a distal region with the ability to negatively regulate basal transcription and a proximal region containing an Sp1 (stimulating protein 1) site that confers approx. 75% of basal transcriptional activity. TRIF expression can be induced by multiple stimuli, such as the ligands for TLR2, TLR3 and TLR4, and by the pro-inflammatory cytokines tumour necrosis factor α and interleukin-1α. All of these stimuli act via an NF-κB (nuclear factor-κB) motif at position −127. In spite of the presence of a STAT1 (signal transduction and activators of transcription 1) motif at position −330, the addition of type I or type II interferon had no effect on TRIF activity. The human TRIF gene would therefore appear to be regulated primarily by NF-κB.
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Research Article|
May 15 2004
Transcriptional regulation of the human TRIF (TIR domain-containing adaptor protein inducing interferon beta) gene
Matthew P. HARDY;
Matthew P. HARDY
1
Department of Biochemistry and Biotechnology Institute, Trinity College, University of Dublin, College Green, Dublin 2, Ireland
1To whom correspondence should be addressed (e-mail hardym@tcd.ie).
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Anne F. McGETTRICK;
Anne F. McGETTRICK
Department of Biochemistry and Biotechnology Institute, Trinity College, University of Dublin, College Green, Dublin 2, Ireland
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Luke A. J. O'NEILL
Luke A. J. O'NEILL
Department of Biochemistry and Biotechnology Institute, Trinity College, University of Dublin, College Green, Dublin 2, Ireland
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Publisher: Portland Press Ltd
Received:
January 06 2004
Revision Received:
February 06 2004
Accepted:
February 09 2004
Accepted Manuscript online:
February 12 2004
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London ©2004
2004
Biochem J (2004) 380 (1): 83–93.
Article history
Received:
January 06 2004
Revision Received:
February 06 2004
Accepted:
February 09 2004
Accepted Manuscript online:
February 12 2004
Citation
Matthew P. HARDY, Anne F. McGETTRICK, Luke A. J. O'NEILL; Transcriptional regulation of the human TRIF (TIR domain-containing adaptor protein inducing interferon beta) gene. Biochem J 15 May 2004; 380 (1): 83–93. doi: https://doi.org/10.1042/bj20040030
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