Identification of the interleukin-6 oncostatin M response element in the rat tissue inhibitor of metalloproteinases-1 (TIMP-1) promoter

被引:105
作者
Bugno, M
Graeve, L
Gatsios, P
Koj, A
Heinrich, PC
Travis, J
Kordula, T
机构
[1] UNIV GEORGIA,DEPT BIOCHEM & MOLEC BIOL,ATHENS,GA 30602
[2] JAGIELLONIAN UNIV,INST MOLEC BIOL,KRAKOW,POLAND
[3] RHEIN WESTFAL TH AACHEN,INST BIOCHEM,W-5100 AACHEN,GERMANY
关键词
D O I
10.1093/nar/23.24.5041
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The rat tissue inhibitor of metalloproteinases 1 (TIMP-1) gene is expressed in rat hepatocytes, and this expression is up-regulated by interleukin 6 (IL-6), We report here the cloning of the 5' flanking region of the rat TIMP-1 gene and identification of an IL-6/oncostatin M (OSM) response element at -64 to -36 which functions in hepatic cells, Within this element we have identified two functional binding sites for transcription factors AP-1 (activatory protein-1) and STAT (signal transducer and activator of transcription), IL-6/OSM stimulation induces binding of a protein, identified as STAT3, to the IL-6/OSM response element, while binding of the AP-1 protein was constitutive, Binding sites for both AP-1 and STAT3 are necessary for full responsiveness of the TIMP-1 promoter to IL-6/OSM, as shown by deletion and mutation analysis, Furthermore, the entire IL-6/OSM response element conferred responsiveness onto a heterologous promoter, whereas this has not been observed when AP-1 and STAT elements were separately tested.
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页码:5041 / 5047
页数:7
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