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. 2008 Jan;45(1):137-43.
doi: 10.1016/j.molimm.2007.04.031. Epub 2007 Jun 18.

Fra-1 and Stat3 synergistically regulate activation of human MMP-9 gene

Yuhua Song  1 , Lu Qian, Santai Song, Liyong Chen, Yan Zhang, Guogang Yuan, Hao Zhang, Qing Xia, Meiru Hu, Ming Yu, Ming Shi, Zefei Jiang, Ning Guo
Affiliations

Fra-1 and Stat3 synergistically regulate activation of human MMP-9 gene

Yuhua Song et al. Mol Immunol. 2008 Jan.

Abstract

Fra-1 is overexpressed in a variety of human tumors. Whether MMP-9 expression is regulated by Fra-1 has been contradictory. To clarify the capability of Fra-1 in activating transcription of MMP-9 gene, we analyzed the transcriptional activity of the MMP-9 promoter through the measure of luciferase activities in the MCF-7 cells transiently transfected with Fra-1. The positive regulation of Fra-1 on MMP-9 promoter was not detectable. By the analysis of MMP-9 promoter, a potential Stat3 binding site, just juxtaposed AP-1 consensus sequence, was noticed. The reporter assay showed that MMP-9 promoter was activated remarkably by cotransfection with Fra-1 and Stat3C. DNA affinity precipitation assay confirmed the binding of Stat3 and Fra-1 to the elements of MMP-9 promoter and also revealed c-Jun recruited to Stat3-Fra-1 complex. By immunoprecipitation assay, the Stat3/Fra-1, Stat3/c-Jun and Fra-1/c-Jun complexes were identified in vivo. Our study demonstrated that the activation of MMP-9 promoter is dependent upon interactions of Fra-1/c-Jun with Stat3. A juxtaposed Stat3/AP-1 element plays a crucial role in the manner of enhancersome in the activation of MMP-9 gene. The functional cooperation of the Stat3 and AP-1 transcription factors is required for the transcription of MMP-9 gene.

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