Source:http://linkedlifedata.com/resource/pubmed/id/11342629
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
10
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pubmed:dateCreated |
2001-5-8
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pubmed:abstractText |
Optimal humoral responses depend on the activation of Ag-specific B cells, followed by their progression toward a fully differentiated phenotype. Acquisition of stage-appropriate patterns of gene expression is crucial to this differentiation program. However, the molecular mechanisms used by B cells to modulate gene expression as they complete their maturation program are poorly understood. IFN-regulatory factor 4 (IRF-4) plays a critical role in mature B cell function. Using the transcriptional regulation of the human B cell activation marker CD23 as a model system, we have previously demonstrated that IRF-4 is induced in response to B cell-activating stimuli and that it acts as a transactivator of CD23 gene expression. We have furthermore found that IRF-4 function can be blocked by B cell lymphomas 6 (BCL-6) protein, a Krüppel-type zinc finger repressor normally expressed in germinal center B cells. However, CD23 expression is known to be down-regulated in plasma cells despite high level expression of IRF-4 and the lack of BCL-6, suggesting that in plasma cells the IRF-4-mediated induction of CD23 is prevented by its interaction with a distinct repressor. In this set of studies, we demonstrate that IRF-4 interacts with B lymphocyte-induced maturation protein/positive regulatory domain I-binding factor 1 (Blimp1/PRD1-BF1), a Krüppel-type zinc finger protein whose expression correlates with terminal B cell differentiation. Functional studies indicate that Blimp1, like BCL-6, can block IRF-4-transactivating ability. These findings thus support a model whereby IRF-4 function is modulated in a stage-specific manner by its interaction with developmentally restricted sets of Krüppel-type zinc finger proteins.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
AIM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Interferon Regulatory Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Interferon-gamma,
http://linkedlifedata.com/resource/pubmed/chemical/PRDM1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, IgE,
http://linkedlifedata.com/resource/pubmed/chemical/Repressor Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Trans-Activators,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/interferon regulatory factor-4
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pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
0022-1767
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
166
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
6104-11
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:11342629-Binding Sites,
pubmed-meshheading:11342629-Cell Differentiation,
pubmed-meshheading:11342629-Cell Line,
pubmed-meshheading:11342629-DNA-Binding Proteins,
pubmed-meshheading:11342629-Humans,
pubmed-meshheading:11342629-Interferon Regulatory Factors,
pubmed-meshheading:11342629-Interferon-gamma,
pubmed-meshheading:11342629-Promoter Regions, Genetic,
pubmed-meshheading:11342629-Receptors, IgE,
pubmed-meshheading:11342629-Repressor Proteins,
pubmed-meshheading:11342629-Trans-Activators,
pubmed-meshheading:11342629-Transcription Factors,
pubmed-meshheading:11342629-Transfection,
pubmed-meshheading:11342629-Tumor Cells, Cultured,
pubmed-meshheading:11342629-U937 Cells,
pubmed-meshheading:11342629-Zinc Fingers
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pubmed:year |
2001
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pubmed:articleTitle |
Stage-specific modulation of IFN-regulatory factor 4 function by Krüppel-type zinc finger proteins.
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pubmed:affiliation |
Department of Medicine, Columbia University, New York, NY 10032, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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