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TGF-beta 1 inhibition of transin/stromelysin gene expression is mediated through a Fos binding sequence
L D Kerr1, D B Miller, L M Matrisian
1Department of Cell Biology, Vanderbilt University, Nashville, Tennessee 37232.
Abstract:
Transforming growth factor beta 1 (TGF-beta 1) inhibits the growth factor and oncogene induction of transin/stromelysin, a secreted matrix-degrading metalloprotease. We demonstrate that a 10 bp element in the transin promoter is required for the TGF-beta 1 inhibitory effects and that this sequence is conserved in the promoter regions of several other TGF-beta 1-inhibited genes. The TGF-beta 1 inhibitory element (TIE) specifically binds a nuclear protein complex from TGF-beta 1-stimulated rat fibroblasts. Interestingly, this complex contained the c-fos proto-oncogene product, Fos, and induction of Fos expression was required for the inhibitory effect of TGF-beta 1 on transin gene expression. These results suggest that TGF-beta 1 inhibition of gene expression is mediated by the binding of a Fos-containing protein complex to the TIE promoter sequences.
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