Abstract
gamma-Synuclein is a small cytoplasmic protein implicated in neurodegenerative diseases and cancer. However, the mechanism of its involvement in diseases is not clear. We studied the role of gamma-synuclein in the regulation of matrix metalloproteinases in retinoblastoma cell culture. Matrix metalloproteinases play important roles in the remodeling of extracellular matrix implicated in tumor progression and in the neurodegenerative diseases. Western blot and zymography data demonstrated a moderate elevation of matrix metalloproteinases-2 and significant upregulation of matrix metalloproteinases-9 in stable cell lines overexpressing gamma-synuclein. No effect of gamma-synuclein overexpression on matrix metalloproteinases-1 level or activity was found. Chloramphenicol-acetyltransferase assay demonstrated that overexpression of gamma-synuclein increases the efficiency of the matrix metalloproteinases-9 promoter. This increment of promoter activity may be mediated by the AP-1 binding site(s), since point mutations in one of these sites (Pr18 or Pr19) and elimination of the distal AP-1 site (Pr14) reduced the increment of promoter activity.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Chloramphenicol O-Acetyltransferase / genetics
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Chloramphenicol O-Acetyltransferase / metabolism
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Gene Expression Regulation
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Humans
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Matrix Metalloproteinase 1 / genetics
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Matrix Metalloproteinase 1 / metabolism
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Matrix Metalloproteinase 2 / genetics
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Matrix Metalloproteinase 2 / metabolism
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Matrix Metalloproteinase 9 / genetics
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Matrix Metalloproteinase 9 / metabolism*
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Mutation
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Nerve Tissue Proteins / genetics
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Nerve Tissue Proteins / metabolism*
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Promoter Regions, Genetic
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Recombinant Proteins / genetics
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Recombinant Proteins / metabolism
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Regulatory Sequences, Nucleic Acid
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Retinal Neoplasms / genetics
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Retinal Neoplasms / metabolism*
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Retinoblastoma / genetics
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Retinoblastoma / metabolism*
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Synucleins
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Tissue Inhibitor of Metalloproteinase-1 / genetics
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Tissue Inhibitor of Metalloproteinase-1 / metabolism
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Tissue Inhibitor of Metalloproteinase-2 / genetics
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Tissue Inhibitor of Metalloproteinase-2 / metabolism
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Transcription Factor AP-1 / genetics
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Transcription Factor AP-1 / metabolism
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Tumor Cells, Cultured
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gamma-Synuclein
Substances
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Nerve Tissue Proteins
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Recombinant Proteins
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Synucleins
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Tissue Inhibitor of Metalloproteinase-1
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Transcription Factor AP-1
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gamma-Synuclein
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Tissue Inhibitor of Metalloproteinase-2
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Chloramphenicol O-Acetyltransferase
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Matrix Metalloproteinase 2
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Matrix Metalloproteinase 9
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Matrix Metalloproteinase 1