Source:http://linkedlifedata.com/resource/pubmed/id/16375605
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
12
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pubmed:dateCreated |
2005-12-26
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pubmed:abstractText |
Both type I interferon (IFN-alpha/beta) and type II IFN (IFN-gamma) exert many functions that are restricted to immune cells. Thus, they play critical roles in innate and adaptive immunity. IFN regulatory factor-4 (IRF-4) and IRF-8 (formerly PU.1 interaction partner [Pip] and IFN consensus sequence binding domain [ICSBP], respectively) are immune cell-specific members of the IRF family that regulate the development of myeloid, lymphoid, and dendritic cells. They form a heterodimeric complex with another immune cell-specific transcription factor PU.1-Spi-1 and regulate transcription of genes in the immune system. This review describes the role of the IRF-8-PU.1 complex in modulating IFN signaling in an immune cell-specific manner. Our studies revealed that some but not all IFN-gamma-inducible genes carry an IFN-gamma activation site (GAS) element that contains a binding site for the IRF- 8-PU.1 complex. The IRF-8-PU.1 complex can take part in GAS-mediated transcription and amplify expression of IFN-gamma-responsive genes initiated by Stat1 in macrophages. Similarly, some but not all IFN-alpha/beta-responsive genes are shown to carry an IFN-stimulated response element (ISRE) that contains an IRF-8-PU.1 binding site. The participation of IRF-8-PU.1 in ISRE-mediated transcription results in the augmentation of IFN-stimulated gene factor 3 (ISGF3)-induced transcription in macrophages. Thus, GAS and ISRE elements, classically defined as universal IFN-alpha/beta and IFN-gamma response sequences, are not the same, and some harbor an embedded motif for IRF- 8-PU.1 binding that functions only in immune cells. Accordingly, the IRF-8-PU.1complex provides secondary IFN signaling pathways unique to the immune system. Collectively, the contribution of IRF-8 and PU.1 to IFN-regulated gene expression may in part account for immune cell-specific functions of IFNs.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/DNA,
http://linkedlifedata.com/resource/pubmed/chemical/Interferon Regulatory Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Interferons,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Trans-Activators,
http://linkedlifedata.com/resource/pubmed/chemical/interferon regulatory factor-4,
http://linkedlifedata.com/resource/pubmed/chemical/interferon regulatory factor-8,
http://linkedlifedata.com/resource/pubmed/chemical/proto-oncogene protein Spi-1
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
1079-9907
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
25
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
770-9
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pubmed:meshHeading |
pubmed-meshheading:16375605-Animals,
pubmed-meshheading:16375605-Base Sequence,
pubmed-meshheading:16375605-DNA,
pubmed-meshheading:16375605-Humans,
pubmed-meshheading:16375605-Interferon Regulatory Factors,
pubmed-meshheading:16375605-Interferons,
pubmed-meshheading:16375605-Proto-Oncogene Proteins,
pubmed-meshheading:16375605-Signal Transduction,
pubmed-meshheading:16375605-Trans-Activators
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pubmed:year |
2005
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pubmed:articleTitle |
Immune cell-specific amplification of interferon signaling by the IRF-4/8-PU.1 complex.
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pubmed:affiliation |
Molecular Immunology and Inflammation Branch, National Institute of Arthritis, Muscuolskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
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pubmed:publicationType |
Journal Article,
Review
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