title: Suppression of matrix metalloproteinase-9 expression in undifferentiated, non-apoptotic keratinocytes is abrogated by the cleavage of poly(ADP-ribose) polymerase-1.
abstract: Matrix metalloproteinase (MMP)-9, an enzyme that degrades the extracellular matrix, has been implicated as a key enzyme in the process of tissue remodeling. This study demonstrates the regulation of MMP-9 transcription through a gene regulatory element in its promoter (the KRE-M9 element). The KRE-M9-binding protein was purified and identified as poly(ADP-ribose) polymerase-1 (PARP-1), which inhibits the transcription of MMP-9 similar to involucrin. This regulation occurs in non-apoptotic keratinocytes using the distinctive culture conditions of high and low Ca(2+) levels. PARP cleavage, which occurs during apoptosis, results in de-repression of MMP-9 promoter activity. These data clarify a new role of PARP-1 and suggest a physiologically relevant connection between caspase activation and MMP-9 expression.
authors.affiliation: Department of Dermatology, National Defense Medical College, Tokorozawa, Saitama, Japan. kobat@ndmc.ac.jp
authors.forename: Takashi
authors.initials: T
authors.lastname: Kobayashi
mesh_terms: D017209:Apoptosis; D001483:Base Sequence; D002118:Calcium; D053148:Caspase 3 / Q000378:metabolism; D002454:Cell Differentiation; D015536:Down-Regulation; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000201:enzymology*; D020780:Matrix Metalloproteinase 9 / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011499:Protein Processing, Post-Translational; D059748:Proteolysis
chemical_list: D011065:Poly(ADP-ribose) Polymerases; D053148:Caspase 3; D020780:Matrix Metalloproteinase 9; D002118:Calcium