The role of AP-1 in matrix metalloproteinase gene expression.
In an effort to understand the mechanism of matrix metalloproteinase (MMP) induction, lapine synoviocytes were isolated and incubated with phorbol myristate acetate (PMA) and autocrine "cell-activating factors" (CAF), agents which significantly increase MMP mRNA abundance. AP-1 complexes, formed by c-fos and c-jun which bind to 5' residues of the MMP genes, seem causally related to MMP gene expression in response to PMA. However, although AP-1 DNA binding activity is strongly induced following exposure of synoviocytes to CAF, MMP gene expression in response to CAF does not correlate well with AP-1 activity and is not inhibited by antisense DNA to fos and jun. We hypothesize that there is a CAF-response factor involved in MMP gene expression and that this factor competes with the binding of the AP-1 complex to its target response element.
Lin
C W
CW
Ferguson Laboratory for Orthopaedic Research, University of Pittsburgh School of Medicine, PA 15261.
Georgescu
H I
HI
Evans
C H
CH
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D015152:Blotting, Northern; D015153:Blotting, Western; D002478:Cells, Cultured; D004790:Enzyme Induction / Q000187:drug effects; D005347:Fibroblasts / Q000166:cytology / Q000201:enzymology; D015870:Gene Expression / Q000187:drug effects* / Q000235:genetics; D019278:Matrix Metalloproteinase 3; D008666:Metalloendopeptidases / Q000235:genetics*; D008969:Molecular Sequence Data; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits; D013583:Synovial Membrane / Q000166:cytology / Q000201:enzymology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D016376:Oligonucleotides, Antisense; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; D008666:Metalloendopeptidases; D019278:Matrix Metalloproteinase 3; D013755:Tetradecanoylphorbol Acetate