Upregulation of the matrix metalloproteinase‐1 gene by the Ewing's sarcoma associated EWS‐ER81 and EWS‐Fli‐1 oncoproteins, c‐Jun and p300

[摘要]

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.

[学科分类] 生物化学/生物物理

[关键词] c-Jun;Ewing's sarcoma;Matrix metalloproteinase-1;p300;Transcription;CTD;C-terminal domain;EWS;Ewing's sarcoma;GST;glutathione S-transferase;MMP;matrix metalloproteinase;NTD;N-terminal domain