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Smooth muscle-specific genes are differentially sensitive to inhibition by Elk-1 总被引:6,自引:0,他引:6
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Understanding the mechanism of smooth muscle cell (SMC) differentiation will provide the foundation for elucidating SMC-related diseases, such as atherosclerosis, restenosis, and asthma. In the current study, overexpression of Elk-1 in SMCs down-regulated expression of several endogenous smooth muscle-restricted proteins, including telokin, SM22α, and smooth muscle α-actin. In contrast, down-regulation of endogenous Elk-1 in smooth muscle cells increased the expression of only telokin and SM22α, suggesting that smooth muscle-specific promoters are differentially sensitive to the inhibitory effects of Elk-1. Consistent with this, overexpression of the DNA binding domain of Elk-1, which acts as a dominant-negative protein by displacing endogenous Elk-1, enhanced the expression of telokin and SM22α without affecting expression of smooth muscle α-actin. Elk-1 suppressed the activity of smooth muscle-restricted promoters, including the telokin promoter that does not contain a consensus Elk-1 binding site, through its ability to block myocardin-induced activation of the promoters. Gel mobility shift and chromatin immunoprecipitation assays revealed that Elk-1 binds to a nonconsensus binding site in the telokin promoter and Elk-1 binding is dependent on serum response factor (SRF) binding to a nearby CArG box. Although overexpression of the SRF-binding B-box domain of Elk-1 is sufficient to repress the myocardin activation of the telokin promoter, this repression is not as complete as that seen with an Elk-1 fragment that includes the DNA binding domain. In addition, reporter gene assays demonstrate that an intact Elk-1 binding site in the telokin promoter is required for Elk-1 to maximally inhibit promoter activity. Together, these data suggest that the differential sensitivity of smooth muscle-specific genes to inhibition by Elk-1 may play a role in the complex changes in smooth muscle-specific protein expression that are observed under pathological conditions. 相似文献
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Regulation of smooth muscle-specific gene expression by homeodomain proteins, Hoxa10 and Hoxb8 总被引:2,自引:0,他引:2
El-Mounayri O Triplett JW Yates CW Herring BP 《The Journal of biological chemistry》2005,280(27):25854-25863
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Physiological control of smooth muscle-specific gene expression through regulated nuclear translocation of serum response factor 总被引:10,自引:0,他引:10
Camoretti-Mercado B Liu HW Halayko AJ Forsythe SM Kyle JW Li B Fu Y McConville J Kogut P Vieira JE Patel NM Hershenson MB Fuchs E Sinha S Miano JM Parmacek MS Burkhardt JK Solway J 《The Journal of biological chemistry》2000,275(39):30387-30393
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