Upregulation of the matrix metalloproteinase-1 gene by the Ewing's sarcoma associated EWS-ER81 and EWS-Fli-1 oncoproteins, c-Jun and p300.
The mechanisms of action of Ewing's sarcoma (EWS) associated EWS-ETS oncoproteins have largely remained unresolved. Here, we analyzed how two EWS-ETS proteins, EWS-ER81 and EWS-Fli-1, in vitro activate the matrix metalloproteinase (MMP)-1 promoter that is upregulated in a subset of EWSs. EWS-ER81 and EWS-Fli-1 interact with and thereby activate the ... MMP-1 promoter, which is potentiated by the cofactor p300 and the proto-oncoprotein c-Jun. Further, EWS-ER81 binds to c-Jun in vitro and in vivo. The interaction between c-Jun, p300 and EWS-ER81 or EWS-Fli-1 may also be relevant to the regulation of other yet-to-be-identified genes that are responsible for EWS formation.
Mesh Terms:
Base Sequence, DNA-Binding Proteins, Electrophoretic Mobility Shift Assay, Enzyme Induction, Humans, Matrix Metalloproteinase 1, Molecular Sequence Data, Nuclear Proteins, Oncogene Proteins, Fusion, Promoter Regions, Genetic, Protein Binding, Proto-Oncogene Protein c-fli-1, Proto-Oncogene Proteins c-jun, RNA-Binding Protein EWS, Sarcoma, Ewing, Trans-Activators, Transcription Factors, Tumor Cells, Cultured
Base Sequence, DNA-Binding Proteins, Electrophoretic Mobility Shift Assay, Enzyme Induction, Humans, Matrix Metalloproteinase 1, Molecular Sequence Data, Nuclear Proteins, Oncogene Proteins, Fusion, Promoter Regions, Genetic, Protein Binding, Proto-Oncogene Protein c-fli-1, Proto-Oncogene Proteins c-jun, RNA-Binding Protein EWS, Sarcoma, Ewing, Trans-Activators, Transcription Factors, Tumor Cells, Cultured
FEBS Lett.
Date: Oct. 09, 2003
PubMed ID: 14550555
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