Source:http://linkedlifedata.com/resource/pubmed/id/10973979
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
47
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pubmed:dateCreated |
2001-1-8
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pubmed:abstractText |
Expression of cytokine genes in T cells is thought to result from a complex network of antigen- and mitogen-activated transcriptional regulators. CP2, a factor homologous to Drosophila Elf-1 and previously found to be a critical regulator of several viral and cellular genes in response to developmental signals, is rapidly activated in T helper (Th) cells in response to mitogenic stimulation. Here we show that overexpression of CP2 enhances interleukin (IL)-4 promoter-driven chloramphenicol acetyltransferase expression, while repressing IL-2 promoter activity, in transiently transfected Jurkat cells. A CP2-protected element, partially overlapping the nuclear factor of activated T cell-binding P2 sequence, was required for IL-4 promoter activation in CP2-overexpressing Jurkat cells. This CP2-response element is the site of a cooperative interaction between CP2 and an inducible heteromeric co-factor(s). Mutation of conserved nucleotide contacts within the CP2-response element prevented CP2 binding and significantly reduced constitutive and induced IL-4 promoter activity. Expression of a CP2 mutant lacking the Elf-1-homology region of the DNA-binding domain inhibited IL-4 promoter activity in a dominant negative fashion in transiently transfected Jurkat cells. Moreover, overexpressed CP2 markedly enhanced, while its dominant negative mutant consistently suppressed, expression of the endogenous IL-4 gene in the murine Th2 cell line D10. Taken together, these findings point to CP2 as a critical IL-4 transactivator in Th cells.
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pubmed:grant | |
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/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-2,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-4,
http://linkedlifedata.com/resource/pubmed/chemical/RNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors
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pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
0021-9258
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
24
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pubmed:volume |
275
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
36605-11
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:10973979-Base Sequence,
pubmed-meshheading:10973979-Consensus Sequence,
pubmed-meshheading:10973979-DNA,
pubmed-meshheading:10973979-DNA-Binding Proteins,
pubmed-meshheading:10973979-Gene Expression Regulation,
pubmed-meshheading:10973979-Humans,
pubmed-meshheading:10973979-Interleukin-2,
pubmed-meshheading:10973979-Interleukin-4,
pubmed-meshheading:10973979-Molecular Sequence Data,
pubmed-meshheading:10973979-Promoter Regions, Genetic,
pubmed-meshheading:10973979-RNA-Binding Proteins,
pubmed-meshheading:10973979-T-Lymphocytes,
pubmed-meshheading:10973979-Transcription Factors
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pubmed:year |
2000
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pubmed:articleTitle |
Identification and characterization of a critical CP2-binding element in the human interleukin-4 promoter.
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pubmed:affiliation |
Department of Medicine, The Johns Hopkins School of Medicine, Baltimore, Maryland 21224, USA. casolaro@mail.jhmi.edu
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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