共查询到20条相似文献,搜索用时 15 毫秒
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Sugimoto H Sugimoto S Tatei K Obinata H Bakovic M Izumi T Vance DE 《The Journal of biological chemistry》2003,278(22):19716-19722
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Ets factors regulate the polycystic kidney disease-1 promoter 总被引:3,自引:0,他引:3
Puri S Rodova M Islam MR Magenheimer BS Maser RL Calvet JP 《Biochemical and biophysical research communications》2006,342(4):1005-1013
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Sampath J Sun D Kidd VJ Grenet J Gandhi A Shapiro LH Wang Q Zambetti GP Schuetz JD 《The Journal of biological chemistry》2001,276(42):39359-39367
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Czuwara-Ladykowska J Shirasaki F Jackers P Watson DK Trojanowska M 《The Journal of biological chemistry》2001,276(24):20839-20848
Fibrosis is characterized by the excessive deposition of extracellular matrix (ECM), especially collagen. Because Ets factors are implicated in physiological and pathological ECM remodeling, the aim of this study was to investigate the role of Ets factors in collagen production. We demonstrate that the expression of collagenous proteins and collagen alpha2(I) (COL1A2) mRNA was inhibited following stable transfection of Fli-1 in dermal fibroblasts. Subsequent analysis of the COL1A2 promoter identified a critical Ets binding site that mediates Fli-1 inhibition. In contrast, Ets-1 stimulates COL1A2 promoter activity. In vitro binding assays demonstrate that both Fli-1 and Ets-1 form DNA-protein complexes with sequences present in COL1A2 promoter. Furthermore, Fli-1 binding to the COL1A2 is enhanced via Sp1-dependent interaction. Studies using Fli-1 dominant interference and DNA binding mutants indicate that Fli-1 inhibition is mediated by both direct (DNA binding) and indirect (via protein-protein interaction) mechanisms and that Sp1 is an important mediator of the Fli-1 function. Furthermore, experiments using the Gal4 system in the context of different cell types as well as experiments with the COL1A2 promoter in different cell lines demonstrate that the direction and magnitude of the effect of Fli-1 is promoter- and cell context-specific. We propose that Fli-1 inhibits COL1A2 promoter activity by competition with Ets-1. In addition, we postulate that another factor (co-repressor) may be required for maximal inhibition after recruitment to the Fli-1-Sp1 complex. We conclude that the ratio of Fli-1 to Ets-1 and the presence of co-regulatory proteins ultimately control ECM production in fibroblasts. 相似文献
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