Nuclear factor‐κB (NF‐κB) represses expression of matrix metalloproteinase‐3 (MMP‐3) by binding to a polymorphic site in the promoter

NF‐κB p50 and p65 were previously shown to bind to a polymorphic (5T/6T) site in the MMP‐3 promoter, along with zinc‐binding protein‐89 (ZBP‐89). This binding site was identified as a repressor element in normal fibroblasts, and recombinant p50 was shown to bind preferentially to the 6T site. This was consistent with other work suggesting that the 6T site is a more effective repressor element. Here we show that in COS‐1 cells the 5T promoter is expressed at a higher basal level than the 6T, as expected. However, the deletion mutant, which was twice as active as the 5T wild‐type in normal fibroblasts, is significantly less active in COS cells. Over‐expressed ZBP‐89 activates the MMP‐3 promoter slightly, but NF‐κB represses both promoters, even in the presence of over‐expressed ZBP‐89. These results show that NF‐κB is a repressor of MMP‐3 expression, and suggest that the role of this polymorphic binding site may be variable, depending on the relative concentrations and activities of the transcription factors that interact with it. This work is supported by grant R15DE16277 from the NIDCR to R.C. Borghaei.