Identification of proteins within the nuclear factor-κB transcriptional complex including estrogen receptor-α

Identification of proteins within the nuclear factor-κB transcriptional complex including estrogen receptor-α
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DOI:
10.1016/j.ajog.2006.12.033
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发表时间:
2007-04-01
影响因子:
9.8
通讯作者:
Leslie, Kimberly K.
Leslie, Kimberly K.
中科院分区:
医学1区
文献类型:
--
作者:
Feldman, Irv;Feldman, Gerald M.;Leslie, Kimberly K.

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目的:这项研究的目的是确定雌激素受体(ER)和核因子-κ B之间是否存在相互作用。(NF-κ B)之间的相互作用,以评估这种ER/NF-κ B相互作用的功能后果,并鉴定可能参与NF-κ B转录复合物的其他未知调节蛋白。电迁移率凝胶位移、报告基因测定和质谱法用于鉴定与NF-κ B脱氧核糖核酸(DNA)反应元件相互作用的蛋白质。ER和NF-κ B B的p65亚基共定位于DNA上。这种相互作用抑制ER转录活性。结合到NF-κ B B/DNA复合物的蛋白质的测序确定了DNA修饰酶,支架蛋白,分子伴侣,和元素的核matrix.CONCLUSION:这些研究已经确定了雌激素受体和NF-κ B的p65亚基之间的抑制性相互作用与雌激素作用在怀孕和癌症的影响。新的辅助蛋白也已被鉴定为结合到NF-κ B DNA反应元件上的蛋白复合物。
OBJECTIVE: The objective of the study was to determine whether cross-talk occurs between estrogen receptors (ERs) and nuclear factor-kappaB (NF-kappa B), to assess the functional consequences of such an ER/NF-kappa B interaction, and to identify other unknown regulatory proteins that may participate in the NF-kappa B transcriptional complex.STUDY DESIGN: Electromobility gel shifts, reporter gene assays, and mass spectrometry were used to identify proteins interacting with the NF-kappa B deoxyribonucleic acid (DNA) response element.RESULTS: ER and the p65 subunit of NF-kappa B colocalized on DNA. This interaction was inhibitory for ER transcriptional activity. Sequencing of proteins bound to the NF-kappa B/DNA complex identified DNA-modifying enzymes, scaffolding proteins, chaperones, and elements of the nuclear matrix.CONCLUSION: These studies have identified an inhibitory interaction between estrogen receptors and the p65 subunit of NF-kappa B with implications for estrogen action in pregnancy and cancer. New accessory proteins have also been identified that bind to protein complexes on the NF-kappa B DNA response element.