NF-kB 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-kB 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-kB in limiting the cytokine induced expression of MMP-3.
Biochemical and biophysical research communications
Borghaei, Ruth C.; Rawlings Jr., P. L.; Javadi, Masoud; and Woloshin, J., "NF-kB binds to a polymorphic repressor element in the MMP-3 promoter" (2004). PCOM Scholarly Papers. 1222.