Abstract
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.
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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Base Sequence
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism*
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Electrophoretic Mobility Shift Assay
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Enzyme Induction
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Humans
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Matrix Metalloproteinase 1 / biosynthesis
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Matrix Metalloproteinase 1 / genetics*
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Molecular Sequence Data
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Nuclear Proteins / metabolism*
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Oncogene Proteins, Fusion / genetics
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Oncogene Proteins, Fusion / metabolism*
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Promoter Regions, Genetic / genetics
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Protein Binding
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Proto-Oncogene Protein c-fli-1
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Proto-Oncogene Proteins c-jun / metabolism*
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RNA-Binding Protein EWS
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Sarcoma, Ewing / metabolism
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Trans-Activators / metabolism*
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Transcription Factors / genetics
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Transcription Factors / metabolism*
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Tumor Cells, Cultured
Substances
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DNA-Binding Proteins
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ETV1 protein, human
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EWS-FLI fusion protein
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Nuclear Proteins
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Oncogene Proteins, Fusion
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Proto-Oncogene Protein c-fli-1
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Proto-Oncogene Proteins c-jun
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RNA-Binding Protein EWS
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Trans-Activators
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Transcription Factors
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Matrix Metalloproteinase 1