L-tryptophan induces expression of collagenase gene in human fibroblasts: demonstration of enhanced AP-1 binding and AP-1 binding site-driven promoter activity.

L. Li*, S. Gotta, A. Mauviel, J. Varga

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

Collagenase, a prototypic matrix metalloproteinase, plays a major role in the degradation of the extracellular matrix. The essential amino acid L-tryptophan was recently shown to stimulate the expression of collagenase gene in human dermal fibroblast cultures. In this study, we focused our attention on the mechanisms responsible for activation of collagenase transcription by L-tryptophan. Incubation of fibroblasts with L-tryptophan resulted in a dose- and time-dependent elevation of collagenase and tissue inhibitor of metalloproteinase mRNA levels. The maximum enhancement in collagenae mRNA was approximately 50-fold. This effect was not abolished by cycloheximide, suggesting independence from ongoing protein synthesis. Transient cell transfections with a promoter/reporter gene construct containing 3.8 kb of 5' flanking DNA of the human collagenase gene linked to the chloramphenicol acetyl transferase (CAT) gene or a construct containing three phorbol ester-responsive AP-1 binding sequences (12-O-tetradecanoyl-phorbol-13-acetate-responsive element) in front of the thymidine kinase promoter linked to the CAT gene indicated enhancement of promoter activity by L-tryptophan. Furthermore, electrophoretic DNA mobility shift assays demonstrated enhanced DNA-protein complex formation specific for an AP-1 binding site probe with nuclear extracts prepared from cells incubated with L-tryptophan. These results collectively suggest that activation of collagenase gene expression in dermal fibroblasts by L-tryptophan is mediated through AP-1 binding elements in the collagenase gene promoter that are sufficient for gene response.

Original languageEnglish (US)
Pages (from-to)361-368
Number of pages8
JournalCellular & molecular biology research
Volume41
Issue number5
StatePublished - 1995

ASJC Scopus subject areas

  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology

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