NF-kappaB binds to a polymorphic repressor element in the MMP-3 promoter.
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.
Department of Biochemistry and Molecular Biology, Philadelphia College of Osteopathic Medicine, 4170 City Avenue, Philadelphia, PA 19131, USA. ruthb@pcom.edu
Ruth C
RC
Borghaei
P Lyle
PL
Rawlings
Masoud
M
Javadi
Joanna
J
Woloshin
D001665:Binding Sites; D004268:DNA-Binding Proteins / Q000378:metabolism; D004794:Enzyme Repression; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D005881:Gingiva / Q000166:cytology; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D019278:Matrix Metalloproteinase 3 / Q000235:genetics*; D016328:NF-kappa B / Q000378:metabolism*; D052002:NF-kappa B p50 Subunit; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D012097:Repressor Proteins / Q000378:metabolism*; D020218:Response Elements; D014157:Transcription Factors / Q000378:metabolism
D004268:DNA-Binding Proteins; D007375:Interleukin-1; D016328:NF-kappa B; D052002:NF-kappa B p50 Subunit; D012097:Repressor Proteins; D014157:Transcription Factors; C110951:ZNF148 protein, human; D019278:Matrix Metalloproteinase 3