NF-κB binds to a polymorphic repressor element in the MMP-3 promoter

被引:62
作者
Borghaei, RC [1 ]
Rawlings, PL [1 ]
Javadi, M [1 ]
Woloshin, J [1 ]
机构
[1] Philadephia Coll Osteopath Med, Dept Biochem & Mol Biol, Philadelphia, PA 19131 USA
关键词
stromelysin-1; ZBP-89; gene expression regulation; NF-kappa B;
D O I
10.1016/j.bbrc.2004.02.030
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
A 5T/6T polymorphic site in the matrix metalloproteinase-3 (MMP-3) promoter has been identified as a repressor element involved in inhibiting induction of MMP-3 transcription by interleukin 1; and the 6T allele has been associated with decreased expression of MMP-3 as compared to the 5T allele. Zinc-binding protein-89 (ZBP-89) was cloned from a yeast one-hybrid assay via its ability to interact with this site, but when the protein was over-expressed, it resulted in activation of the MMP-3 promoter rather than repression. Here we show that in nuclear extracts isolated from human gingival fibroblasts stimulated with IL-1, this site is bound by p50 and p65 components of NF-kappaB in addition to ZBP-89, and that recombinant p50 binds preferentially to the 6T binding site. These results are consistent with a role for NF-kappaB in limiting the cytokine induced expression of MMP-3. (C) 2004 Elsevier Inc. All rights reserved.
引用
收藏
页码:182 / 188
页数:7
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