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    • 4. 发明授权
    • Methods and compositions for the detection and isolation of ligands
    • 用于检测和分离配体的方法和组合物
    • US08236937B2
    • 2012-08-07
    • US12158383
    • 2006-12-22
    • Henry M. KrauseJens Tiefenbach
    • Henry M. KrauseJens Tiefenbach
    • A01K67/027
    • A61K49/0008C07K2319/43C07K2319/715C07K2319/80C12Q1/6897G01N2500/02
    • A method for the detection and isolation of ligands, preferably nuclear receptor ligands, bound to their cognate receptors in live animals, is described. A novel composition comprising 1) a chimeric transcription factor containing a DNA-binding domain, preferably from a non-vertebrate transcription factor, fused to the ligand-binding domain (LBD) of a nuclear receptor, 2) a reporter system, driven by a promoter that contains binding sites for the chosen DNA-binding domain, 3) multiple affinity tags fused to the LBD fusion proteins to facilitate efficient purification, along with specifically associated molecules and 4) sequences required for simultaneous genomic integration of all three components above are described. To make use of the system, expression of the chimeric LBD protein is broadly induced.
    • 描述了用于检测和分离与活体动物中的其同源受体结合的配体,优选核受体配体的方法。 一种新型组合物,其包含1)嵌合转录因子,其含有与核受体的配体结合结构域(LBD)融合的DNA结合结构域,优选来自非脊椎动物转录因子,2)报告系统,由 描述了包含所选DNA结合结构域的结合位点的启动子,3)与LBD融合蛋白融合以促进有效纯化的多个亲和标签以及特异性相关分子以及4)上述所有三种组分的同时基因组整合所需的序列 。 为了利用该系统,广泛诱导了嵌合LBD蛋白的表达。
    • 6. 发明申请
    • Horming response element binding transregulators
    • Horming响应元件结合式跨越器
    • US20070192880A1
    • 2007-08-16
    • US10574322
    • 2004-10-04
    • Mesut MuyanJing Huang
    • Mesut MuyanJing Huang
    • A01K67/027A61K48/00C07H21/04C12P21/06C07K14/82
    • C12N15/62C07K14/4702C07K2319/715C12N2799/022C12N2830/008
    • Disclosed are compositions and methods for ERE-binding tansregulators that specifically and potently regulate ERE-containing genes. To accomplish this, we took advantage of the modular nature of ER and initially designed a monomeric ERE binding module by co-joining two DNA binding domains with the hinge domain. Integradon of strong activation or repressor domains from other transcription factors into this module generated constitutively active ERE-binding activators (EBAs) and ERE-binding repressors (EBRs) respectively. These novel transregulators are the basis for the targeted regulation of ERE containing genes, the identification of estrogen reponsive gene networks, and the development of alternative/complementary therapeutic approaches for estrogen target tissue cancers.
    • 公开了特异性和有效调节含ERE的基因的ERE结合的调节物的组合物和方法。 为了实现这一点,我们利用了ER的模块化特性,并最初通过将两个DNA结合结构域与铰链域共同连接来设计单体ERE结合模块。 来自其他转录因子的强激活或抑制子结构域的整合体分别产生组成型活性ERE结合激活因子​​(EBAs)和ERE结合阻遏物(EBRs)。 这些新型跨越调控因子是靶向调控含ERE基因,雌激素反应基因网络的鉴定以及雌激素靶组织癌的替代/补充治疗方法的发展的基础。
    • 10. 发明授权
    • Heterodimeric nuclear receptors proteins, genes encoding same, and usage thereof
    • 异二聚体核受体蛋白,编码相同的基因及其用途
    • US06635429B1
    • 2003-10-21
    • US08216592
    • 1994-03-23
    • Mark LeidPhilippe KastnerPierre Chambon
    • Mark LeidPhilippe KastnerPierre Chambon
    • G01N3353
    • C07K14/70567C07K2319/715C07K2319/80
    • The present invention is based in part on the novel observation that two different types of nuclear receptors, retinoic acid receptors (RAR) and thyroid receptors (TR) dimerize with a RX receptor (RXR) to form a heterodimer which is capable of binding to retinoic acid response elements (RARE) or thyroid receptor response elements (TRE) at physiological conditions. In addition, the present invention discloses that RXR homodimers are capable of binding to RARE's. Based on this observation, the present invention provides novel dimeric proteins, methods of identifying agents capable of binding the dimers of the present invention, methods of identifying DNA sequences capable of being bound by the dimers and methods to identify RA metabolic enzymes and proteins which are required for the activation function of nuclear receptors.
    • 本发明部分基于两种不同类型的核受体,视黄酸受体(RAR)和甲状腺受体(TR)与RX受体(RXR)二聚化以形成能够结合视黄酸的异源二聚体的新观察 酸反应元素(RARE)或甲状腺受体反应元件(TRE)。 另外,本发明公开了RXR同型二聚体能够与RARE结合。 基于该观察,本发明提供了新颖的二聚蛋白,鉴定能够结合本发明的二聚体的试剂的方法,鉴定能够被二聚体结合的DNA序列的方法以及鉴定RA代谢酶和蛋白质的方法 核受体激活功能所需。