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.
Fuchs
Bruno
B
Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN 55905, USA.
Inwards
Carrie Y
CY
Janknecht
Ralf
R
D001483:Base Sequence; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D024202:Electrophoretic Mobility Shift Assay; D004790:Enzyme Induction; D006801:Humans; D020781:Matrix Metalloproteinase 1 / Q000096:biosynthesis / Q000235:genetics*; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000378:metabolism*; D015514:Oncogene Proteins, Fusion / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D051789:Proto-Oncogene Protein c-fli-1; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism*; D034802:RNA-Binding Protein EWS; D012512:Sarcoma, Ewing / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; C095239:ETV1 protein, human; C106031:EWS-FLI fusion protein; D009687:Nuclear Proteins; D015514:Oncogene Proteins, Fusion; D051789:Proto-Oncogene Protein c-fli-1; D016755:Proto-Oncogene Proteins c-jun; D034802:RNA-Binding Protein EWS; D015534:Trans-Activators; D014157:Transcription Factors; D020781:Matrix Metalloproteinase 1