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    Heterodimer complex of RXR and NURR1 or NGFI-B
    5.
    发明授权
    Heterodimer complex of RXR and NURR1 or NGFI-B 失效
    RXR和NURR1或NGFI-B的异二聚体复合物

    公开(公告)号：US06458926B1

    公开(公告)日：2002-10-01

    申请号：US08877966

    申请日：1997-06-18

    申请人： Ronald M. Evans ,  Barry M. Forman ,  Kazuhiko Umesono

    发明人： Ronald M. Evans ,  Barry M. Forman ,  Kazuhiko Umesono

    IPC分类号： C07K14435

    CPC分类号： C07K14/70567 ,  C07K2319/00 ,  G01N33/6875 ,  G01N33/74

    摘要： Heterodimerization is a common paradigm among eucaryotic transcription factors, though it remains unclear how individual monomers contribute to the overall transcriptional activities of the complex. The 9-cis retinoic acid receptor (RXR) serves as a common heterodimerization partner for several nuclear receptors including the thyroid hormone (T3R), retinoic acid (RAR) and vitamin D receptors. A strategy has been devised to examine the transcriptional properties of each receptor individually or when tethered to a heterodimeric partner. It has been found that the intrinsic activity of RXR is masked in RXR-T3R and RXR-RAR heterodimers. In contrast, a novel RXR-Nurr1 heterodimer described herein is highly responsive to RXR ligands, suggesting that different partners exert unique allosteric control over the RXR response. These findings establish a novel 9-cis retinoic acid response pathway and resolve the paradox as to how T3R, RAR and VDR contribute to distinct physiologic pathways while sharing a common RXR subunit.

    摘要翻译： 异源二聚化是真核转录因子中的常见范例，尽管单个单体如何有助于复合物的整体转录活性仍不清楚。 9-顺式视黄酸受体（RXR）用作几种核受体（包括甲状腺激素（T3R），视黄酸（RAR）和维生素D受体）的常见异源二聚体配偶体。 已经设计出一种策略来单独检测每个受体的转录特性，或者当连接到异二聚体配偶体时。 已经发现在RXR-T3R和RXR-RAR异二聚体中RXR的固有活性被掩蔽。 相比之下，本文描述的新型RXR-Nurr1异源二聚体对RXR配体具有高度响应性，表明不同的合作伙伴对RXR应答发挥独特的变构控制。 这些研究结果建立了一种新的9-顺式视黄酸反应途径，并解决了T3R，RAR和VDR如何在共享一个共同的RXR亚基时对不同的生理途径有贡献的矛盾。

    Retinoic acid receptor composition
    7.
    发明授权
    Retinoic acid receptor composition 失效
    视黄酸受体组成

    公开(公告)号：US5274077A

    公开(公告)日：1993-12-28

    申请号：US975777

    申请日：1992-11-13

    申请人： Ronald M. Evans ,  Estelita S. Ong ,  Prudimar S. Segui ,  Catherine C. Thompson ,  Kazuhiko Umesono ,  Vincent Giguere

    发明人： Ronald M. Evans ,  Estelita S. Ong ,  Prudimar S. Segui ,  Catherine C. Thompson ,  Kazuhiko Umesono ,  Vincent Giguere

    IPC分类号： C07K14/705 ,  C12N15/12 ,  C12Q1/68 ,  C07K13/00

    CPC分类号： C07K14/70567 ,  C12Q1/6897 ,  C07K2319/61 ,  C07K2319/715 ,  C07K2319/81

    摘要： A novel retinoic acid receptor is disclosed. The novel receptor is encoded for by CDNA carried on plasmid phRAR1, which has been deposited with the American Type Culture Collection for patent purposes. Chimeric receptor proteins are also disclosed. The chimera are constructed by exchanging functional domains between the glucocorticoid, the mineralocorticoid, the estrogen-related, the thyroid and the retinoic acid receptors. In addition, a novel method for identifying functional ligands for receptor proteins is disclosed. The method, which takes advantage of the modular structure of the hormone receptors and the idea that the functional domains may be interchangeable, replaces the DNA-binding domain of a putative novel receptor with the DNA-binding domain of a known receptor such as the glucocorticoid receptor. The resulting chimeric construction, when expressed in cells, produces a hybrid receptor whose activation of a ligand--(e.g., glucocorticoid) inducible promoter is dependent on the presence of the new ligand. The novel method is illustrated in part by showing that the ligand for the new receptor protein is the retinoid, retinoic acid.

    摘要翻译： 公开了一种新型视黄酸受体。 新型受体由携带在质粒phRAR1上的CDNA编码，其已经用美国典型培养物保藏中心专利保藏。 还公开了嵌合受体蛋白。 通过在糖皮质激素，盐皮质激素，雌激素相关，甲状腺和视黄酸受体之间交换功能结构来构建嵌合体。 另外，公开了用于鉴定受体蛋白质的功能性配体的新方法。 利用激素受体的模块化结构的方法和功能域可以互换的想法将已知受体的DNA结合结构域（例如糖皮质激素）替代推定的新受体的DNA结合结构域 受体。 当在细胞中表达时，产生的嵌合构型产生杂合受体，其配体（例如，糖皮质激素）诱导型启动子的活化取决于新配体的存在。 该新方法部分地通过显示新受体蛋白质的配体是类视黄醇，视黄酸来说明。

    Response element compositions and assays employing same
    8.
    发明授权
    Response element compositions and assays employing same 失效
    响应元素组合物和采用其的测定法

    公开(公告)号：US06492137B1

    公开(公告)日：2002-12-10

    申请号：US07672530

    申请日：1991-03-19

    申请人： Henry M. Sucov ,  Ronald M. Evans ,  Kazuhiko Umesono

    发明人： Henry M. Sucov ,  Ronald M. Evans ,  Kazuhiko Umesono

    IPC分类号： C12P2102

    CPC分类号： C07K14/70567 ,  C07K14/721 ,  C12N15/85 ,  C12N2800/108 ,  C12N2830/002 ,  C12N2830/008 ,  C12N2830/30 ,  C12N2830/38 ,  C12N2830/60 ,  C12N2830/85 ,  C12Q1/6897 ,  G01N33/5008 ,  G01N33/502 ,  G01N33/5023 ,  G01N33/5041 ,  G01N33/743

    摘要： DNA segments have been discovered, and characterized by sequence, which are response elements operative to confer responsiveness to ligands for several members of the steroid/thyroid superfamily of receptors, for the transcriptional activation and/or repression of promoters in cells. By using transcriptional control regions comprising response elements of the present invention in combination with a functional promoter, it is now possible to provide recombinant DNA vectors containing a gene, the transcription (and, thereby, also expression) of which is under the control of a promoter, the transcriptional activity of which is responsive to ligands for members of the steroid/thyroid superfamily of receptors.

    摘要翻译： 已经发现了DNA区段，其特征在于序列，其是作用于赋予类固醇/甲状腺超家族受体的若干成员对配体的反应性的响应元件，用于细胞中启动子的转录激活和/或抑制。 通过使用包含本发明的响应元件与功能启动子组合的转录控制区，现在可以提供含有基因的重组DNA载体，其转录（并且由此也由其表达）处于一个 启动子，其转录活性对受体的类固醇/甲状腺超家族成员的配体有反应。

    Hormone response element compositions and assay
    9.
    发明授权
    Hormone response element compositions and assay 失效
    激素反应元件组成和测定

    公开(公告)号：US5597693A

    公开(公告)日：1997-01-28

    申请号：US494618

    申请日：1990-03-16

    申请人： Ronald M. Evans ,  Kazuhiko Umesono

    发明人： Ronald M. Evans ,  Kazuhiko Umesono

    IPC分类号： C07K7/06 ,  C07K14/00 ,  C07K14/435 ,  C07K14/705 ,  C07K14/72 ,  C12N15/09 ,  C12P21/02 ,  C12Q1/68 ,  C12R1/91

    CPC分类号： C12Q1/6897 ,  C07K14/721

    摘要： The present invention discloses steroid/thyroid hormone receptor DNA binding domain compositions that determine target gene specificity. The invention further discloses methods converting the target gene specificity of one receptor into the target gene specificity of another. Still further the invention discloses novel assays for identifying ligands for orphan hormone receptors. These assays are especially useful since they avoid the necessity of constructing chimeric genes and proteins in order to search for ligands that can activate a putative receptor.

    摘要翻译： 本发明公开了确定靶基因特异性的类固醇/甲状腺激素受体DNA结合结构域组合物。 本发明还公开了将一种受体的靶基因特异性转化为另一种受体的靶基因特异性的方法。 本发明进一步公开了用于鉴定孤儿激素受体配体的新型测定法。 这些测定是特别有用的，因为它们避免了构建嵌合基因和蛋白质的需要，以便搜索可以激活推定受体的配体。

    Response element compositions and assays employing same
    10.
    发明授权
    Response element compositions and assays employing same 失效
    响应元素组合物和采用其的测定法

    公开(公告)号：US07189510B2

    公开(公告)日：2007-03-13

    申请号：US10302557

    申请日：2002-11-22

    申请人： Henry M. Sucov ,  Ronald M. Evans ,  Kazuhiko Umesono

    发明人： Henry M. Sucov ,  Ronald M. Evans ,  Kazuhiko Umesono

    IPC分类号： C12Q1/68

    CPC分类号： C07K14/70567 ,  C07K14/721 ,  C12N15/85 ,  C12N2800/108 ,  C12N2830/002 ,  C12N2830/008 ,  C12N2830/30 ,  C12N2830/38 ,  C12N2830/60 ,  C12N2830/85 ,  C12Q1/6897 ,  G01N33/5008 ,  G01N33/502 ,  G01N33/5023 ,  G01N33/5041 ,  G01N33/743

    摘要： DNA segments have been discovered, and characterized by sequence, which are response elements operative to confer responsiveness to ligands for several members of the steroid/thyroid superfamily of receptors, for the transcriptional activation and/or repression of promoters in cells. By using transcriptional control regions comprising response elements of the present invention in combination with a functional promoter, it is now possible to provide recombinant DNA vectors containing a gene, the transcription (and, thereby, also expression) of which is under the control of a promoter, the transcriptional activity of which is responsive to ligands for members of the steroid/thyroid superfamily of receptors.

    摘要翻译： 已经发现了DNA区段，其特征在于序列，其是作用于赋予类固醇/甲状腺超家族受体的若干成员对配体的反应性的响应元件，用于细胞中启动子的转录激活和/或抑制。 通过使用包含本发明的响应元件与功能启动子组合的转录控制区，现在可以提供含有基因的重组DNA载体，其转录（并且由此也由其表达）处于一个 启动子，其转录活性对受体的类固醇/甲状腺超家族成员的配体有反应。