Liver enriched transcription factor
    2.
    发明授权
    Liver enriched transcription factor 失效
    肝脏丰富的转录因子

    公开(公告)号:US5849485A

    公开(公告)日:1998-12-15

    申请号:US661330

    申请日:1996-06-14

    摘要: HNF-4 (hepatocyte nuclear factor 4) is a protein enriched in liver extracts that binds to sites required for the transcription of the transthyretin (TTR) and apolipoprotein CIII (apoCIII) genes (Costa et al., 1989; Costa et al., 1990; Leff et al., 1989). We have purified HNF-4 protein (54 kD) and isolated a cDNA clone encoding the protein. HNF-4 is a member of the steroid hormone receptor superfamily with an unusual amino acid in the conserved "knuckle" of the first zinc finger (DGCKG). This and the fact that HNF-4 does not bind significantly to estrogen, thyroid hormone or glucocorticoid response elements indicate that HNF-4 may represent a new subfamily. HNF-4 binds to its recognition site as a dimer and activates transcription in a sequence-specific fashion in nonhepatic (HeLa) cells. HNF-4 mRNA is present in kidney and intestine as well as liver but is absent in other tissues. DNA binding data suggest that HNF-4 could be identical to liver factor A1 (LF-A1), a factor previously shown to regulate the transcription of the .alpha.-1 antitrypsin, apolipoprotein A1 and pyruvate kinase genes.

    摘要翻译: HNF-4(肝细胞核因子4)是富含肝脏提取物的蛋白质,其结合转甲状腺素蛋白(TTR)和载脂蛋白CIII(apoCIII)基因转录所需的位点(Costa et al。,1989; Costa et al。 1990; Leff等人,1989)。 我们纯化HNF-4蛋白(54 kD),分离出一个编码蛋白质的cDNA克隆。 HNF-4是类固醇激素受体超家族的成员,其在第一锌指(DGCKG)的保守“指关节”中具有不寻常的氨基酸。 这和HNF-4与雌激素,甲状腺激素或糖皮质激素反应元件不显着结合的事实表明,HNF-4可能代表一个新的亚家族。 HNF-4作为二聚体结合其识别位点,并以非特异性(HeLa)细胞中的序列特异性方式激活转录。 HNF-4 mRNA存在于肾和肠以及肝脏中,但在其他组织中不存在。 DNA结合数据表明HNF-4可以与肝脏因子A1(LF-A1)相同,这是以前显示的调节α-1抗胰蛋白酶,载脂蛋白A1和丙酮酸激酶基因转录的因子。

    Liver enriched transcription factor
    3.
    发明授权
    Liver enriched transcription factor 失效
    肝脏丰富的转录因子

    公开(公告)号:US07368293B2

    公开(公告)日:2008-05-06

    申请号:US10215597

    申请日:2002-08-09

    IPC分类号: C01N33/00 C01N33/566

    CPC分类号: C07K14/4702 A61K38/00

    摘要: HNF-4 (hepatocyte nuclear factor 4) is a protein enriched in liver extracts that binds to sites required for the transcription of the transthyretin (TTR) and apolipoprotein CIII (apoCIII) genes (Costa et al., 1989; Costa et al., 1990; Leff et al., 1989). We have purified HNF-4 protein (54 kD) and isolated a cDNA clone encoding the protein. HNF-4 is a member of the steroid hormone receptor superfamily with an unusual amino acid in the conserved “knuckle” of the first zinc finger (DGCKG). This and the fact that HNF-4 does not bind significantly to estrogen, thyroid hormone or glucocorticoid response elements indicate that HNF-4 may represent a new subfamily. HNF-4 binds to its recognition site as a dimer and activates transcription in a sequence-specific fashion in nonhepatic (HeLa) cells. HNF-4 mRNA is present in kidney and intestine as well as liver but is absent in other tissues. DNA binding data suggest that HNF-4 could be identical to liver factor A1 (LF-A1), a factor previously shown to regulate the transcription of the α-1 antitrypsin, apolipoprotein A1 and pyruvate kinase genes.

    摘要翻译: HNF-4(肝细胞核因子4)是富含肝脏提取物的蛋白质,其结合转甲状腺素蛋白(TTR)和载脂蛋白CIII(apoCIII)基因转录所需的位点(Costa et al。,1989; Costa et al。 1990; Leff等人,1989)。 我们纯化HNF-4蛋白(54 kD),分离出一个编码蛋白质的cDNA克隆。 HNF-4是类固醇激素受体超家族的成员,其在第一锌指(DGCKG)的保守“指关节”中具有不寻常的氨基酸。 这和HNF-4与雌激素,甲状腺激素或糖皮质激素反应元件不显着结合的事实表明,HNF-4可能代表一个新的亚家族。 HNF-4作为二聚体结合其识别位点,并以非特异性(HeLa)细胞中的序列特异性方式激活转录。 HNF-4 mRNA存在于肾和肠以及肝脏中,但在其他组织中不存在。 DNA结合数据表明HNF-4可以与肝脏因子A1(LF-A1)相同,这是以前显示的调节α-1抗胰蛋白酶,载脂蛋白A1和丙酮酸激酶基因转录的因子。

    Liver enriched transcription factor
    4.
    发明授权
    Liver enriched transcription factor 失效
    肝脏丰富的转录因子

    公开(公告)号:US5604115A

    公开(公告)日:1997-02-18

    申请号:US078222

    申请日:1993-10-28

    摘要: HNF-4 (hepatocyte nuclear factor 4) is a protein enriched in liver extracts that binds to sites required for the transcription of the transthyretin (TTR) and apolipoprotein CIII (apoCIII) genes (Costa et al., 1989; Costa et al., 1990; Leff et al., 1989). We have purified HNF-4 protein (54 kD) and isolated a cDNA clone encoding the protein. HNF-4 is a member of the steroid hormone receptor superfamily with an unusual amino acid in the conserved "knuckle" of the first zinc finger (DGCKG). This and the fact that HNF-4 does not bind significantly to estrogen, thyroid hormone or glucocorticoid response elements indicate that HNF-4 may represent a new subfamily. HNF-4 binds to its recognition site as a dimer and activates transcription in a sequence-specific fashion in nonhepatic (HeLa) cells. HNF-4 mRNA is present in kidney and intestine as well as liver but is absent in other tissues. DNA binding data suggest that HNF-4 could be identical to liver factor A1 (LF-A1), a factor previously shown to regulate the transcription of the .alpha.-1 antitrypsin, apolipoprotein A1 and pyruvate kinase genes.

    摘要翻译: PCT No.PCT / US91 / 09733 Sec。 371日期:1993年10月28日 102(e)日期1993年10月28日PCT 1991年12月23日PCT公布。 第WO92 / 11365号PCT公告 日期1992年9月7日HNF-4(肝细胞核因子4)是富含肝提取物的蛋白质,其结合转甲状腺素蛋白(TTR)和载脂蛋白CIII(apoCIII)基因转录所需的位点(Costa et al。,1989; Costa et al。,1990; Leff et al。,1989)。 我们纯化HNF-4蛋白(54 kD),分离出一个编码蛋白质的cDNA克隆。 HNF-4是类固醇激素受体超家族的成员,其在第一锌指(DGCKG)的保守“指关节”中具有不寻常的氨基酸。 这和HNF-4与雌激素,甲状腺激素或糖皮质激素反应元件不显着结合的事实表明,HNF-4可能代表一个新的亚家族。 HNF-4作为二聚体结合其识别位点,并以非特异性(HeLa)细胞的序列特异性方式激活转录。 HNF-4 mRNA存在于肾和肠以及肝脏中,但在其他组织中不存在。 DNA结合数据表明HNF-4可以与肝脏因子A1(LF-A1)相同,这是以前显示的调节α-1抗胰蛋白酶,载脂蛋白A1和丙酮酸激酶基因转录的因子。

    Liver enriched transcription factor
    5.
    发明授权
    Liver enriched transcription factor 失效
    肝脏丰富的转录因子

    公开(公告)号:US06500672B1

    公开(公告)日:2002-12-31

    申请号:US09447034

    申请日:1999-11-22

    IPC分类号: C01N3300

    摘要: HNF-4 (hepatocyte nuclear factor 4) is a protein enriched in liver extracts that binds to sites required for the transcription of the transthyretin (TTR) and apolipoprotein CIII (apoCIII) genes (Costa et al., 1989; Costa et al., 1990; Leff et al., 1989). We have purified HNF-4 protein (54 kD) and isolated a cDNA clone encoding the protein. HNF-4 is a member of the steroid hormone receptor superfamily with an unusual amino acid in the conserved “knuckle” of the first zinc finger (DGCKG). This and the fact that HNF-4 does not bind significantly to estrogen, thyroid hormone or glucocorticoid response elements indicate that HNF-4 may represent a new subfamily. HNF-4 binds to its recognition site as a dimer and activates transcription in a sequence-specific fashion in nonhepatic (HeLa) cells. HNF-4 mRNA is present in kidney and intestine as well as liver but is absent in other tissues. DNA binding data suggest that HNF-4 could be identical to liver factor A1 (LF-A1), a factor previously shown to regulate the transcription of the &agr;-1 antitrypsin, apolipoprotein A1 and pyruvate kinase genes.

    摘要翻译: HNF-4(肝细胞核因子4)是富含肝脏提取物的蛋白质,其结合转甲状腺素蛋白(TTR)和载脂蛋白CIII(apoCIII)基因转录所需的位点(Costa et al。,1989; Costa et al。 1990; Leff等人,1989)。 我们纯化HNF-4蛋白(54 kD),分离出一个编码蛋白质的cDNA克隆。 HNF-4是类固醇激素受体超家族的成员,在第一锌指(DGCKG)的保守“指关节”中具有不寻常的氨基酸。 这和HNF-4与雌激素,甲状腺激素或糖皮质激素反应元件不显着结合的事实表明,HNF-4可能代表一个新的亚家族。 HNF-4作为二聚体结合其识别位点,并以非特异性(HeLa)细胞中的序列特异性方式激活转录。 HNF-4 mRNA存在于肾和肠以及肝脏中,但在其他组织中不存在。 DNA结合数据表明HNF-4可以与肝脏因子A1(LF-A1)相同,这是以前显示的调节α-1抗胰蛋白酶,载脂蛋白A1和丙酮酸激酶基因转录的因子。

    Purified Stat proteins and methods of purifying thereof
    6.
    发明授权
    Purified Stat proteins and methods of purifying thereof 失效
    纯化的Stat蛋白及其纯化方法

    公开(公告)号:US07417120B2

    公开(公告)日:2008-08-26

    申请号:US11335005

    申请日:2006-01-19

    IPC分类号: C07K1/00

    摘要: The present invention describes methods of producing milligram quantities of three forms of purified Stat1 protein from recombinant DNA constructs. In addition, the Stat proteins may be isolated in their phosphorylated or nonphosphorylated forms (Tyr 701). The proteins can be produced in baculovirus infected insect cells, or E. coli. A compact domain in the amino terminus of Stat1α was isolated and found to enhance DNA binding due to its ability to interact with a neighboring Stat protein. A relatively protease-resistant recombinant truncated form of the Stat protein was isolated in 40-50 mg quantities. Purification of the Stat proteins were performed after modifying specific cysteine residues of the Stat proteins to prevent aggregation. Activated EGF-receptor partially purified from membranes by immunoprecipitation was shown to be capable of in vitro catalysis of the phosphorylation of the tyrosine residue of Stat1 known to be phosphorylated in vivo. Techniques are enclosed to separate the phosphorylated from the nonphosphorylated Stat proteins. The techniques disclosed are general for Stat proteins and may be used to isolate large quantities of purified Stat 2, 3, 4, 5A, 5B and 6. Methods for using purified Stat proteins, truncated Stat proteins, or Stat N-terminal fragments for drug discovery are also disclosed.

    摘要翻译: 本发明描述了从重组DNA构建体产生毫克量的三种形式的纯化的Stat1蛋白的方法。 此外,Stat蛋白可以以其磷酸化或非磷酸化形式(Tyr 701)分离。 蛋白质可以在杆状病毒感染的昆虫细胞或大肠杆菌中产生。 分离Stat1alpha氨基末端的紧密结构域,由于其与邻近Stat蛋白质相互作用的能力,发现DNA结合增强。 以40-50mg的量分离相对蛋白酶的重组截短形式的Stat蛋白。 Stat蛋白的纯化在Stat蛋白的特异性半胱氨酸残基修饰后进行,以防止聚集。 通过免疫沉淀从膜部分纯化的活化的EGF受体显示能够体外催化已知在体内被磷酸化的Stat1的酪氨酸残基的磷酸化。 封闭技术以将磷酸化的非磷酸化Stat蛋白分离。 所公开的技术对于Stat蛋白是普遍的,并且可以用于分离大量纯化的Stat2,3,4,5A,5B和6.使用纯化的Stat蛋白,截短的Stat蛋白或Stat N末端片段进行药物的方法 发现也被披露。

    Nucleic acids encoding receptor recognition factors, and methods of use thereof
    7.
    发明授权
    Nucleic acids encoding receptor recognition factors, and methods of use thereof 失效
    编码受体识别因子的核酸及其使用方法

    公开(公告)号:US07339039B2

    公开(公告)日:2008-03-04

    申请号:US09876773

    申请日:2001-06-07

    IPC分类号: C07H21/04 C12P21/06 C07K14/00

    摘要: Receptor recognition factors exist that recognizes the specific cell receptor to which a specific ligand has been bound, and that may thereby signal and/or initiate the binding of the transcription factor to the DNA site. The receptor recognition factor is in one instance, a part of a transcription factor, and also may interact with other transcription factors to cause them to activate and travel to the nucleus for DNA binding. The receptor recognition factor appears to be second-messenger-independent in its activity, as overt perturbations in second messenger concentrations are of no effect. The concept of the invention is illustrated by the results of studies conducted With interferon (IFN)-stimulated gene transcription, and particularly, the activation caused by both IFNα and IFNγ. Specific DNA and amino acid sequences for various human and murine receptor recognition factors are provided, as are polypeptide fragments of two of the ISGF-3 genes, and antibodies have also been prepared and tested. The polypeptides confirm direct involvement of tyrosine kinase in intracellular message transmission. Numerous diagnostic and therapeutic materials and utilities are also disclosed.

    摘要翻译: 存在识别特异性配体已被结合的特异性细胞受体的受体识别因子,从而可以将转录因子与DNA位点的结合信号和/或启动。 受体识别因子在一个例子中是转录因子的一部分,并且还可以与其他转录因子相互作用,以使其激活并前往细胞核进行DNA结合。 受体识别因子似乎在其活动中是与第二信使无关的,因为第二信使浓度的明显的扰动是无效的。 通过用干扰素(IFN)刺激的基因转录,特别是由IFNα和IFNγ引起的活化的研究结果说明了本发明的概念。 提供了各种人和鼠受体识别因子的特异性DNA和氨基酸序列,两种ISGF-3基因的多肽片段也已经被制备和测试。 这些多肽证实了酪氨酸激酶在细胞内消息传播中的直接参与。 还公开了许多诊断和治疗材料和效用。

    Nucleic acids encoding receptor recognition factor stat 3 and methods of
use thereof
    9.
    发明授权
    Nucleic acids encoding receptor recognition factor stat 3 and methods of use thereof 失效
    编码受体识别因子stat 3的核酸及其使用方法

    公开(公告)号:US6030808A

    公开(公告)日:2000-02-29

    申请号:US956869

    申请日:1997-10-23

    摘要: Receptor recognition factors exist that recognizes the specific cell receptor to which a specific ligand has been bound, and that may thereby signal and/or initiate the binding of the transcription factor to the DNA site. The receptor recognition factor is in one instance, a part of a transcription factor, and also may interact with other transcription factors to cause them to activate and travel to the nucleus for DNA binding. The receptor recognition factor appears to be second-messenger-independent in its activity, as overt perturbations in second messenger concentrations are of no effect. The concept of the invention is illustrated by the results of studies conducted with interferon (IFN)-stimulated gene transcription, and particularly, the activation caused by both IFN.alpha. and IFN-.gamma.. Specific DNA and amino acid sequences for various human and murine receptor recognition factors are provided, as are polypeptide fragments of two of the ISGF-3 genes, and antibodies have also been prepared and tested. The polypeptides confirm direct involvement of tyrosine kinase in intracellular message transmission. Numerous diagnostic and therapeutic materials and utilities are also disclosed.

    摘要翻译: 存在识别特异性配体已被结合的特异性细胞受体的受体识别因子,从而可以将转录因子与DNA位点的结合信号和/或启动。 受体识别因子在一个例子中是转录因子的一部分,并且还可以与其他转录因子相互作用,以使其激活并前往细胞核进行DNA结合。 受体识别因子似乎在其活动中是与第二信使无关的,因为第二信使浓度的明显的扰动是无效的。 通过用干扰素(IFN)刺激的基因转录进行的研究结果,特别是由IFNα和IFN-γ引起的活化来说明本发明的概念。 提供了各种人和鼠受体识别因子的特异性DNA和氨基酸序列,两种ISGF-3基因的多肽片段也已经被制备和测试。 这些多肽证实了酪氨酸激酶在细胞内消息传播中的直接参与。 还公开了许多诊断和治疗材料和效用。

    Methods of testing drugs or agents that modulate the activity of receptor recognition factors
    10.
    发明授权
    Methods of testing drugs or agents that modulate the activity of receptor recognition factors 失效
    测试调节受体识别因子活性的药物或药剂的方法

    公开(公告)号:US06605442B1

    公开(公告)日:2003-08-12

    申请号:US08212185

    申请日:1994-03-11

    IPC分类号: G01N3353

    摘要: Receptor recognition factors exist that recognizes the specific cell receptor to which a specific ligand has been bound, and that may thereby signal and/or initiate the binding of the transcription factor to the DNA site. The receptor recognition factor is in one instance, a part of a transcription factor, and also may interact with other transcription factors to cause them to activate and travel to the nucleus for DNA binding. The receptor recognition factor appears to be second-messenger-independent in its activity, as overt perturbations in second messenger concentrations are of no effect. The concept of the invention is illustrated by the results of studies conducted with interferon (IFN)-stimulated gene transcription, and particularly, the activation caused by both IFN&agr; and IFN&ggr;. Specific DNA and amino acid sequences for various human and murine receptor recognition factors are provided, as are polypeptide fragments of two of the ISGF-3 genes, and antibodies have also been prepared and tested. The polypeptides confirm direct involvement of tyrosine kinase in intracellular message transmission. Numerous diagnostic and therapeutic materials and utilities are also disclosed.

    摘要翻译: 存在识别特异性配体已被结合的特异性细胞受体的受体识别因子,从而可以将转录因子与DNA位点的结合信号和/或启动。 受体识别因子在一个例子中是转录因子的一部分,并且还可以与其他转录因子相互作用,以使其激活并前往细胞核进行DNA结合。 受体识别因子似乎在其活动中是与第二信使无关的,因为第二信使浓度的明显的扰动是无效的。 通过用干扰素(IFN)刺激的基因转录进行的研究结果,特别是由IFNα和IFNγ引起的活化来说明本发明的概念。 提供了各种人和鼠受体识别因子的特异性DNA和氨基酸序列,两种ISGF-3基因的多肽片段也已经被制备和测试。 这些多肽证实了酪氨酸激酶在细胞内消息传播中的直接参与。 还公开了许多诊断和治疗材料和效用。