Regulating expression of the gene for matrix metalloproteinase-1 (collagenase): mechanisms that control enzyme activity, transcription, and mRNA stability.
Crit Rev Eukaryot Gene Expr
; 6(4): 391-411, 1996.
Article
em En
| MEDLINE
| ID: mdl-8959374
ABSTRACT
Matrix metalloproteinase-1 (MMP-1) is one of three collagenases that can degrade the interstitial collagens, types I, II, and III at neutral pH. As these collagens are the most abundant proteins in the body, collagenase plays a critical role in modeling and remodeling the extracellular matrix. Therefore, it is not surprising that MMP-1 gene expression can be regulated at multiple points. Procollagenase can be activated by mechanisms that generate an active enzyme with differing specific activities, and the active enzyme can be inhibited by complexing with either the tissue inhibitor of metalloproteinases (TIMPs) or alpha 2 macroglobulin. The activator protein-1 (AP-1) site in the collagenase promoter plays a prominent role in the transcriptional control of the collagenase gene. It is essential for basal transcription, and contributes to induction by phorbol esters, although other sites in the proximal promoter are essential. In contrast, transactivation by cytokines such as Interleukin-1 depends on sequences in more distal regions of the promoter. Posttranscriptional mechanisms also regulate gene expression, and several cytokines and growth factors increase the stability of the collagenase transcript. Finally, glucocorticoid hormones repress transcription of the collagenase gene by the interaction of glucocorticoid receptors with the AP-1 proteins, Fos and Jun. Retinoids also suppress transcription by mechanisms that involve down-regulation of fos and jun mRNA, sequestration of Fos and Jun proteins, and the formation of complexes of retinoic acid receptors (RAR/RXR heterodimers) and AP-1 proteins on the DNA. These multiple points of regulation assure precise control of collagenolytic activity in a variety of physiologic and pathologic conditions.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Regulação da Expressão Gênica
/
Colagenases
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Crit Rev Eukaryot Gene Expr
Assunto da revista:
BIOLOGIA MOLECULAR
/
BIOTECNOLOGIA
Ano de publicação:
1996
Tipo de documento:
Article
País de afiliação:
Estados Unidos