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CN1671843B - 参与转录调控的因子 - Google Patents

参与转录调控的因子 Download PDF

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CN1671843B
CN1671843B CN038178338A CN03817833A CN1671843B CN 1671843 B CN1671843 B CN 1671843B CN 038178338 A CN038178338 A CN 038178338A CN 03817833 A CN03817833 A CN 03817833A CN 1671843 B CN1671843 B CN 1671843B
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dna
peptide
transcription
sequence
sequence shown
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CN1671843A (zh
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水谷修纪
山田孝之
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Sony Corp
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
    • C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
    • C07K14/4701—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals not used
    • C07K14/4702—Regulators; Modulating activity
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
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    • C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
    • C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
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    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity

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Abstract

HDART结合于HDAC(组蛋白脱乙酰基酶)并起到阻遏物的作用。同样，HDART直接结合于起核内受体共活化物作用的Skip，以抑制核内受体的转录。并且，HDART能结合于作为核内受体的转录共阻遏物之一的HDAC，由此强烈的抑制通过HDAC的组蛋白脱乙酰作用的转录。另一方面，获得了一种HDART的显性阴性肽，并证实该肽活化转录，与全长HDART蛋白作用相反。特别是，该肽在活化视黄酸受体转录的活性方面优于全反式视黄酸(ATRA)。

Description

参与转录调控的因子
技术领域
本发明涉及转录调控因子等等，更具体地，涉及能控制核激素受体引起的转录的因子或肽。
背景技术
激素，脂溶性维生素等在生物的稳定维持、能量代谢、分化、生长等方面起着重要的作用。这些激素的受体等是存在于核内的转录调控因子，并且与染色质DNA的特定位点结合从而控制基因的转录反应。在大多数情况下，当配体如激素等不与受体结合时，转录的发生将会受到抑制。一旦配体(如激素)与受体结合，转录将通过染色质结构的改变而活化。据报道，从核内受体到转录装置(transcriptor)的路程中，许多称作共活化物(co-activator)和共阻遏物(co-repressor)的因子形成复合体。配体未结合型受体与包含组蛋白脱乙酰基酶的共阻遏物结合，从而抑制基因表达。另一方面，当受体结构经过与配体的结合而发生变化时，共阻遏物复合体被释放，包含组蛋白乙酰基转移酶的共活化物复合体被募集(recruited)。比如Skip共活化物(即Ski相互作用蛋白，也称作N-CoA62)，它直接结合于某些类型的核内受体(比如维生素3受体，视黄酸受体，雌激素受体以及糖皮质激素受体)以增强由这些核内受体引起的基因表达(Baudino，T.A.，Kraichely，D.M.，Jefcoat，S.C.，Jr.，winchester，S.K.，Partridge，N.C.，and MacDonald，P.N.(1998)J.Biol Chem 273(26)，16434-41，MacDonaldo，P.N.，Baudio，T.A.，Tokumaru，H.，Dowd，D.R.，and Zhang，C.(2001)Streoids 66(3-5)，171-6)。发明内容

Claims (10)

1.编码能活化转录的肽的DNA，包括(A)编码由序列2的第1-179位所示氨基酸序列组成的肽的DNA，或(B)由序列1的第1-537位碱基所示碱基序列组成的DNA。
2.转录活化肽，由权利要求1的DNA编码。
3.载体，插入了权利要求1的DNA。
4.宿主细胞，具有权利要求1的DNA或权利要求3的载体。
5.抗体，能结合权利要求2的肽。
6.基板，固定了以下(A)至(B)之一：
(A)权利要求2的转录活化肽；
(B)权利要求5的抗体。
7.具有SEQ IDNO：2所示氨基酸序列的蛋白质或由序列1编码的蛋白质在制备抑制转录的药物中的用途。
8.肽在制备活化转录的药物中的用途，所述肽由序列2的第1-179位所示氨基酸序列组成或由序列1的第1-537位所示碱基序列编码。
9.权利要求7或8的用途，其中所述转录是由核激素受体引起的。
10.DNA在制备治疗由核受体转录的增加/降低导致的疾病的药物中的用途，其中所述DNA是编码转录抑制因子的DNA，包括：
(A)编码具有序列2所示氨基酸序列的蛋白的DNA，或
(B)由序列1所示碱基序列组成的DNA。
CN038178338A 2002-07-25 2003-07-25 参与转录调控的因子 Expired - Fee Related CN1671843B (zh)

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JP2002217233 2002-07-25
JP217233/2002 2002-07-25
PCT/JP2003/009443 WO2004031388A1 (ja) 2002-07-25 2003-07-25 転写調節に関与する因子

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EP (1) EP1541685B1 (zh)
JP (1) JP4508872B2 (zh)
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JP4265402B2 (ja) * 2001-09-25 2009-05-20 ソニー株式会社 ｐ３００ヒストンアセチル化酵素インヒビターを含む転写阻害用組成物及び該ｐ３００ヒストンアセチル化酵素インヒビターを阻害し得る阻害物質のスクリーニング方法
US7154002B1 (en) 2002-10-08 2006-12-26 Takeda San Diego, Inc. Histone deacetylase inhibitors
US7169801B2 (en) 2003-03-17 2007-01-30 Takeda San Diego, Inc. Histone deacetylase inhibitors
WO2006066133A2 (en) 2004-12-16 2006-06-22 Takeda San Diego, Inc. Histone deacetylase inhibitors
US7642253B2 (en) 2005-05-11 2010-01-05 Takeda San Diego, Inc. Histone deacetylase inhibitors
WO2007011626A2 (en) 2005-07-14 2007-01-25 Takeda San Diego, Inc. Histone deacetylase inhibitors

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WO2001007471A2 (en) * 1999-07-21 2001-02-01 Incyte Genomics, Inc. Cell cycle and proliferation proteins
CN1309135A (zh) * 2000-02-17 2001-08-22 上海市肿瘤研究所 具有抑制癌细胞生长功能的新的人蛋白及其编码序列
WO2001064834A2 (en) * 2000-02-28 2001-09-07 Hyseq, Inc. Novel nucleic acids and polypeptides

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US6593456B1 (en) * 1996-11-06 2003-07-15 The Regents Of The University Of California Tumor necrosis factor receptor releasing enzyme
CA2383592A1 (en) * 1999-03-31 2000-10-05 Curagen Corporation 2384891 acids including open reading frames encoding polypeptides; orfx
US20050048623A1 (en) * 1999-07-21 2005-03-03 Incyte Corporation Cell cycle and proliferation proteins
CN1160370C (zh) * 2000-02-17 2004-08-04 上海市肿瘤研究所 新的人细胞周期控制相关蛋白及其编码序列
JP4265402B2 (ja) * 2001-09-25 2009-05-20 ソニー株式会社 ｐ３００ヒストンアセチル化酵素インヒビターを含む転写阻害用組成物及び該ｐ３００ヒストンアセチル化酵素インヒビターを阻害し得る阻害物質のスクリーニング方法

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2001007471A2 (en) * 1999-07-21 2001-02-01 Incyte Genomics, Inc. Cell cycle and proliferation proteins
CN1309135A (zh) * 2000-02-17 2001-08-22 上海市肿瘤研究所 具有抑制癌细胞生长功能的新的人蛋白及其编码序列
WO2001064834A2 (en) * 2000-02-28 2001-09-07 Hyseq, Inc. Novel nucleic acids and polypeptides

Non-Patent Citations (4)

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NAKATSUY..XAB2 a novel tetratricopeptide repeat protein involved intranscription-coupled DNA repair and transcription.THE JOURNAL OF BIOLOGICAL CHEMISTRY275 45.2000
陈坚.组蛋白乙酰化/脱乙酰化与细胞周期的关系.国外医学遗传学分册23 5.2000,23(5),233-236.
陈坚.组蛋白乙酰化/脱乙酰化与细胞周期的关系.国外医学遗传学分册23 5.2000,23(5),233-236. *

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EP1541685B1 (en) 2011-10-26
WO2004031388A1 (ja) 2004-04-15
AU2003252693A1 (en) 2004-04-23
CN1671843A (zh) 2005-09-21
US20120088301A1 (en) 2012-04-12
JP4508872B2 (ja) 2010-07-21
JPWO2004031388A1 (ja) 2006-02-02
EP1541685A1 (en) 2005-06-15
KR101083852B1 (ko) 2011-11-15
KR20050034720A (ko) 2005-04-14
EP1541685A4 (en) 2006-05-24
US8889408B2 (en) 2014-11-18
US20080145928A1 (en) 2008-06-19

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