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Genes Cells. 1996 Nov;1(11):995-1005.

Regulation of IFN-alpha/beta genes: evidence for a dual function of the transcription factor complex ISGF3 in the production and action of IFN-alpha/beta.

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1
Department of Immunology, Faculty of Medicine, University of Tokyo, Hongo, Japan.

Abstract

BACKGROUND:

Efficient production of interferons (IFNs) in virally infected cells is an essential aspect of the host defence. The transcription factor complex ISGF3 (IFN-stimulated gene factor 3) was originally identified as a critical mediator of the IFN signal; it is formed upon IFN receptor (IFNR) stimulation and binds to ISREs (IFN-stimulated response elements) to activate IFN-inducible genes. It has recently been shown that the DNA binding component of ISGF3, p48 (ISGF3gamma) also binds to virus-inducible elements in the IFN-alpha/beta genes, suggesting a potential new role of p48 in IFN production.

RESULTS:

Primary cells from mice with a targeted disruption of the p48 gene show severe defects in virus-induced IFN-alpha/beta gene expression. A similar defect was also observed in cells lacking type I IFNR or Stat1, further demonstrating the role of IFN signalling in the induction of these IFN genes. ISGF3 in fact binds to the virus-inducible elements within the IFN-alpha/beta promoters. We also provide evidence showing that these elements are additionally controlled by an unidentified factor(s) which presumably triggers the primary phase of IFN gene induction.

CONCLUSIONS:

Our results demonstrate that the IFN signal transducing complex ISGF3 plays a crucial role in IFN production and suggest that ISGF3 may participate directly in the activation of IFN-alpha/beta promoters. This dual function of ISGF3 may insure the efficient operation of this cytokine system in the host defence.

PMID:
9077462
[Indexed for MEDLINE]
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