Transcriptional control of matrix metalloproteinases and the tissue inhibitors of matrix metalloproteinases.
Matrix metalloproteinases (MMPs) are enzymes with important roles in a variety of normal physiological processes; these same enzymes are also operative in a range of pathologies. The proteins known as the tissue inhibitors of matrix metalloproteinases (TIMPs) act to limit the enzymatic function of the MMPs. MMPs and TIMPs can be divided into two groups with respect to gene expression: the majority exhibit inducible expression and a small number are produced constitutively or are expressed at very low levels and are not inducible. Among the agents that induce MMP and TIMP production are the inflammatory cytokines TNF alpha and IL1 beta. A marked cell type specificity is a hallmark of both MMP and TIMP gene expression (i.e., a limited number of cell types can be induced to make these proteins). An analysis of the control elements in the promoter regions of these proteins reveals a correlation between the presence of both AP-1 and Ets binding sites and inducible expression. The chromosomal locations of most of the MMPs and TIMPs have been verified; these data will provide the basis for investigations into possible correlations between mutations in these genes and disease states.
Borden
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Institute of Biochemistry and Cell Biology, Syntex Discovery Research, Palo Alto, CA 94304, USA.
Heller
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D000818:Animals; D001665:Binding Sites; D002874:Chromosome Mapping; D017364:Collagenases / Q000378:metabolism; D005786:Gene Expression Regulation; D015971:Gene Expression Regulation, Enzymologic; D006023:Glycoproteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D011480:Protease Inhibitors / Q000378:metabolism; D019714:Tissue Inhibitor of Metalloproteinases; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic
D006023:Glycoproteins; D011480:Protease Inhibitors; D019714:Tissue Inhibitor of Metalloproteinases; D014157:Transcription Factors; D017364:Collagenases; D008666:Metalloendopeptidases