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Identification of two factors required for transcription of the ovalbumin gene. 总被引:29,自引:10,他引:19
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I Sagami S Y Tsai H Wang M J Tsai B W O''''Malley 《Molecular and cellular biology》1986,6(12):4259-4267
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Protein-protein interactions facilitate DNA binding by the glucocorticoid receptor DNA-binding domain 总被引:10,自引:0,他引:10
K Dahlman-Wright H Siltala-Roos J Carlstedt-Duke J A Gustafsson 《The Journal of biological chemistry》1990,265(23):14030-14035
We have studied the interaction of the DNA-binding domain of the glucocorticoid receptor with a glucocorticoid response element from the tyrosine aminotransferase gene. This response element consists of two binding sites (half-sites) for the glucocorticoid receptor DNA-binding domain. The sequences of these two half-sites are not identical, and we have previously shown that binding occurs preferentially to one of the half-sites (Tsai, S.-Y., Carlstedt-Duke, J., Weigel, N. L., Dahlman, K., Gustafsson, J.-A., Tsai, M.-J., and O'Malley, B. W. (1988) Cell 55, 361-369). We show here that binding to the low affinity half-site is dependent on previous occupancy of the high affinity half-site. This facilitated binding is dependent on the distance between the two half-sites and their relative orientation but is not dependent on the integrity of the DNA backbone. This is consistent with a model where DNA binding is not only dependent on interactions between the protein and its DNA target sequence but is also influenced by interactions between the protein molecules bound. 相似文献
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T J Berrodin M S Marks K Ozato E Linney M A Lazar 《Molecular endocrinology (Baltimore, Md.)》1992,6(9):1468-1478
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O'Malley BW 《Molecular endocrinology (Baltimore, Md.)》2005,19(6):1402-1411
The O'Malley laboratory first showed that estrogen and progesterone act in the nucleus to stimulate synthesis of specific mRNAs (ovalbumin and avidin), coding for their respective inducible proteins. The overall molecular pathway of steroid-receptor-DNA-mRNA-protein-function was then established and provided a coherent foundation for future studies of the impact of estrogen and progesterone receptors on endocrine tissue development, adult function, and in pathologies such as cancer. The lab group went on to: biochemically demonstrate ligand-induced conformational activation of progesterone and estrogen receptors, discover the concept of ligand-independent activation of steroid receptors, discover key steroid receptor coactivator intermediary coactivators for receptor function, and define the role of coactivators/corepressors in selective receptor modulator drug action and in cell homeostasis. This body of work advanced our molecular understanding of the critical role of steroid hormones in normal and abnormal physiology and also generated a base of scientific knowledge that served to further modern hormonal therapy and disease management. 相似文献
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