|
rdf:type |
|
|
lifeskim:mentions |
|
|
pubmed:issue |
20
|
|
pubmed:dateCreated |
2003-5-12
|
|
pubmed:abstractText |
Following induction and activation of the early growth response (Egr)-1 transcription factor in human chondrocytes, interleukin-1beta (IL-1beta) suppresses the expression of the type II collagen gene (COL2A1), associated with induction of Egr-1 binding activity in nuclear extracts. The COL2A1 proximal promoter contains overlapping binding sites for Egr-1 and Sp1 family members at -119/-112 bp and -81/-74 bp. Mutations that block binding of Sp1 and Sp3 to either site markedly reduce constitutive expression of the core promoter. IL-1beta-induced Egr-1 binds strongly to the -119/-112 bp site, and mutations that block Egr-1 binding prevent inhibition by IL-1beta. Cotransfection with pCMV-Egr1 potentiates the inhibition of COL2A1 promoter activity by IL-1beta, whereas overexpression of dominant-negative Egr-1 mutant, Wilm's tumor-1 (WT1)/Egr1, Sp1, or Sp3 reverses the inhibition by IL-1beta. Cotransfection of pGL2-COL2/Gal4, in which we substituted the critical residue for Egr-1 binding with a Gal4 binding domain and a pCMV-Gal4-Egr1 chimera permits an inhibitory response to IL-1beta that is reversed by overexpression of Gal4-CBP. Our results indicate that IL-1beta-induced activation of Egr-1 binding is required for inhibition of COL2A1 proximal promoter activity and suggest that Egr-1 acts as a repressor of a constitutively expressed collagen gene by preventing interactions between Sp1 and the general transcriptional machinery.
|
|
pubmed:grant |
|
|
pubmed:language |
eng
|
|
pubmed:journal |
|
|
pubmed:citationSubset |
IM
|
|
pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/COL2A1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Collagen,
http://linkedlifedata.com/resource/pubmed/chemical/Collagen Type II,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/EGR1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Early Growth Response Protein 1,
http://linkedlifedata.com/resource/pubmed/chemical/Egr1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Immediate-Early Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-1,
http://linkedlifedata.com/resource/pubmed/chemical/Luciferases,
http://linkedlifedata.com/resource/pubmed/chemical/RNA,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Fusion Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Sp1 Transcription Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors
|
|
pubmed:status |
MEDLINE
|
|
pubmed:month |
May
|
|
pubmed:issn |
0021-9258
|
|
pubmed:author |
|
|
pubmed:issnType |
Print
|
|
pubmed:day |
16
|
|
pubmed:volume |
278
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
|
pubmed:pagination |
17688-700
|
|
pubmed:dateRevised |
2008-11-21
|
|
pubmed:meshHeading |
pubmed-meshheading:12637574-Amino Acid Motifs,
pubmed-meshheading:12637574-Binding Sites,
pubmed-meshheading:12637574-Blotting, Western,
pubmed-meshheading:12637574-Cell Line,
pubmed-meshheading:12637574-Cell Nucleus,
pubmed-meshheading:12637574-Chondrocytes,
pubmed-meshheading:12637574-Collagen,
pubmed-meshheading:12637574-Collagen Type II,
pubmed-meshheading:12637574-DNA-Binding Proteins,
pubmed-meshheading:12637574-Early Growth Response Protein 1,
pubmed-meshheading:12637574-Humans,
pubmed-meshheading:12637574-Immediate-Early Proteins,
pubmed-meshheading:12637574-Interleukin-1,
pubmed-meshheading:12637574-Luciferases,
pubmed-meshheading:12637574-Models, Genetic,
pubmed-meshheading:12637574-Mutagenesis, Site-Directed,
pubmed-meshheading:12637574-Mutation,
pubmed-meshheading:12637574-Plasmids,
pubmed-meshheading:12637574-Promoter Regions, Genetic,
pubmed-meshheading:12637574-Protein Binding,
pubmed-meshheading:12637574-Protein Structure, Tertiary,
pubmed-meshheading:12637574-RNA,
pubmed-meshheading:12637574-RNA, Messenger,
pubmed-meshheading:12637574-Recombinant Fusion Proteins,
pubmed-meshheading:12637574-Sp1 Transcription Factor,
pubmed-meshheading:12637574-Time Factors,
pubmed-meshheading:12637574-Transcription, Genetic,
pubmed-meshheading:12637574-Transcription Factors,
pubmed-meshheading:12637574-Transcriptional Activation,
pubmed-meshheading:12637574-Transfection
|
|
pubmed:year |
2003
|
|
pubmed:articleTitle |
Egr-1 mediates transcriptional repression of COL2A1 promoter activity by interleukin-1beta.
|
|
pubmed:affiliation |
Rheumatology Division, Beth Israel Deaconess Medical Center and New England Baptist Bone & Joint Institute, Harvard Institutes of Medicine, Boston, Massachusetts 02115, USA.
|
|
pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
|
