• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

维甲酸X受体同型二聚体的形成导致T3反应的抑制：通过配体诱导的抑制作用实现激素间的相互作用。

Formation of retinoid X receptor homodimers leads to repression of T3 response: hormonal cross talk by ligand-induced squelching.

作者信息

Lehmann J M, Zhang X K, Graupner G, Lee M O, Hermann T, Hoffmann B, Pfahl M

机构信息

Cancer Center, La Jolla Cancer Research Foundation, California 92037.

出版信息

Mol Cell Biol. 1993 Dec;13(12):7698-707. doi: 10.1128/mcb.13.12.7698-7707.1993.

DOI:10.1128/mcb.13.12.7698-7707.1993
PMID:8246986
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC364841/
Abstract

Thyroid hormone receptors (TRs) form heterodimers with retinoid X receptors (RXRs). Heterodimerization is required for efficient TR DNA binding to most response elements and transcriptional activation by thyroid hormone. RXRs also function as auxiliary proteins for several other receptors. In addition, RXR alpha can be induced by specific ligands to form homodimers. Here we report that RXR-specific retinoids that induce RXR homodimers are effective repressors of the T3 response. We provide evidence that this repression by RXR-specific ligands occurs by sequestering of RXR from TR-RXR heterodimers into RXR homodimers. This ligand-induced squelching may represent an important mechanism by which RXR-specific retinoids and 9-cis retinoic acid mediate hormonal cross talk among a subfamily of nuclear receptors activated by structurally unrelated ligands.

摘要

甲状腺激素受体（TRs）与视黄酸X受体（RXRs）形成异源二聚体。异源二聚化是TR有效结合大多数反应元件以及甲状腺激素进行转录激活所必需的。RXRs还作为其他几种受体的辅助蛋白发挥作用。此外，RXRα可被特定配体诱导形成同源二聚体。在此我们报告，诱导RXR同源二聚体的RXR特异性类视黄醇是T3反应的有效抑制剂。我们提供的证据表明，RXR特异性配体的这种抑制作用是通过将RXR从TR-RXR异源二聚体中隔离到RXR同源二聚体中而发生的。这种配体诱导的抑制可能代表了一种重要机制，通过该机制，RXR特异性类视黄醇和9-顺式视黄酸介导了由结构不相关配体激活的核受体亚家族之间的激素相互作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/58fc/364841/79a5767d38c7/molcellb00024-0516-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/58fc/364841/a2aec4b88f99/molcellb00024-0513-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/58fc/364841/b133620139c1/molcellb00024-0514-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/58fc/364841/79a5767d38c7/molcellb00024-0516-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/58fc/364841/a2aec4b88f99/molcellb00024-0513-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/58fc/364841/b133620139c1/molcellb00024-0514-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/58fc/364841/79a5767d38c7/molcellb00024-0516-a.jpg

相似文献

1
Formation of retinoid X receptor homodimers leads to repression of T3 response: hormonal cross talk by ligand-induced squelching.维甲酸X受体同型二聚体的形成导致T3反应的抑制：通过配体诱导的抑制作用实现激素间的相互作用。
Mol Cell Biol. 1993 Dec;13(12):7698-707. doi: 10.1128/mcb.13.12.7698-7707.1993.
2
The ligand-binding domains of the thyroid hormone/retinoid receptor gene subfamily function in vivo to mediate heterodimerization, gene silencing, and transactivation.甲状腺激素/视黄酸受体基因亚家族的配体结合结构域在体内发挥作用，介导异源二聚化、基因沉默和反式激活。
Mol Cell Biol. 1995 Mar;15(3):1817-25. doi: 10.1128/MCB.15.3.1817.
3
Modulation of thyroid hormone action by mutant thyroid hormone receptors, c-erbA alpha 2 and peroxisome proliferator-activated receptor: evidence for different mechanisms of inhibition.突变型甲状腺激素受体、c-erbAα2和过氧化物酶体增殖物激活受体对甲状腺激素作用的调节：抑制机制不同的证据
Mol Cell Endocrinol. 1995 Jan;107(1):55-66. doi: 10.1016/0303-7207(94)03422-p.
4
Interaction of human beta 1 thyroid hormone receptor and its mutants with DNA and retinoid X receptor beta. T3 response element-dependent dominant negative potency.人β1甲状腺激素受体及其突变体与DNA和视黄酸X受体β的相互作用。T3反应元件依赖性显性负性效力。
J Clin Invest. 1993 Oct;92(4):1986-93. doi: 10.1172/JCI116793.
5
A shift in the ligand responsiveness of thyroid hormone receptor alpha induced by heterodimerization with retinoid X receptor alpha.甲状腺激素受体α与视黄酸X受体α异源二聚化诱导的配体反应性转变。
Mol Cell Biol. 1996 Jan;16(1):219-27. doi: 10.1128/MCB.16.1.219.
6
Homodimer and heterodimer DNA binding and transcriptional responsiveness to triiodothyronine (T3) and 9-cis-retinoic acid are determined by the number and order of high affinity half-sites in a T3 response element.同二聚体和异二聚体与DNA的结合以及对三碘甲状腺原氨酸（T3）和9-顺式视黄酸的转录反应性，由T3反应元件中高亲和力半位点的数量和顺序决定。
J Biol Chem. 1994 Mar 25;269(12):8863-71.
7
Novel roles of retinoid X receptor (RXR) and RXR ligand in dynamically modulating the activity of the thyroid hormone receptor/RXR heterodimer.维甲酸X受体（RXR）和RXR配体在动态调节甲状腺激素受体/RXR异二聚体活性中的新作用。
J Biol Chem. 2004 Feb 27;279(9):7427-37. doi: 10.1074/jbc.M311596200. Epub 2003 Dec 10.
8
Heterodimeric receptor complexes determine 3,5,3'-triiodothyronine and retinoid signaling specificities.异二聚体受体复合物决定了3,5,3'-三碘甲状腺原氨酸和类视黄醇信号特异性。
Mol Endocrinol. 1992 Jul;6(7):1153-62. doi: 10.1210/mend.6.7.1324421.
9
Similar ligand-induced conformational changes of thyroid hormone receptors regulate homo- and heterodimeric functions.甲状腺激素受体类似的配体诱导构象变化调节同源和异源二聚体功能。
J Biol Chem. 1995 Feb 17;270(7):3107-14. doi: 10.1074/jbc.270.7.3107.
10
A permissive retinoid X receptor/thyroid hormone receptor heterodimer allows stimulation of prolactin gene transcription by thyroid hormone and 9-cis-retinoic acid.一种允许性的视黄酸X受体/甲状腺激素受体异二聚体可使甲状腺激素和9-顺式视黄酸刺激催乳素基因转录。
Mol Cell Biol. 2004 Jan;24(2):502-13. doi: 10.1128/MCB.24.2.502-513.2004.

引用本文的文献

1
Sex alters thyroid hormone's effect on protein O-GlcNAcylation in the aged mouse heart.性别改变甲状腺激素对老年小鼠心脏中蛋白质O-连接N-乙酰葡糖胺化的影响。
BMC Mol Cell Biol. 2025 Jun 10;26(1):19. doi: 10.1186/s12860-025-00543-x.
2
An Isochroman Analog of CD3254 and Allyl-, Isochroman-Analogs of NEt-TMN Prove to Be More Potent Retinoid-X-Receptor (RXR) Selective Agonists Than Bexarotene.一种异喹啉类似物 CD3254 和 NEt-TMN 的烯丙基异喹啉类似物被证明比贝沙罗汀更能有效作为维甲酸 X 受体（RXR）的选择性激动剂。
Int J Mol Sci. 2022 Dec 19;23(24):16213. doi: 10.3390/ijms232416213.
3
Modeling, Synthesis, and Biological Evaluation of Potential Retinoid-X-Receptor (RXR) Selective Agonists: Analogs of 4-[1-(3,5,5,8,8-Pentamethyl-5,6,7,8-tetrahyro-2-naphthyl)ethynyl]benzoic Acid (Bexarotene) and 6-(Ethyl(4-isobutoxy-3-isopropylphenyl)amino)nicotinic Acid (NEt-4IB).

本文引用的文献

1
V-erbA requires auxiliary proteins for dominant negative activity.V-erbA发挥显性负性活性需要辅助蛋白。
Oncogene. 1993 Jan;8(1):55-65.
2
Effects of vitamin A and its analogs (retinoids) on normal and neoplastic cells.维生素A及其类似物（类视黄醇）对正常细胞和肿瘤细胞的作用。
Biochim Biophys Acta. 1980 Mar 12;605(1):33-91. doi: 10.1016/0304-419x(80)90021-9.
3
Cardiac alpha- and beta-myosin heavy chain genes are organized in tandem.心脏α和β肌球蛋白重链基因串联排列。
潜在维甲酸 X 受体（RXR）选择性激动剂的建模、合成与生物评价：4-[1-(3,5,5,8,8-五甲基-5,6,7,8-四氢-2-萘基)乙炔基]苯甲酸（贝沙罗汀）和 6-(乙基(4-异丁氧基-3-异丙基苯基)氨基)烟酸（NEt-4IB）类似物
Int J Mol Sci. 2021 Nov 16;22(22):12371. doi: 10.3390/ijms222212371.
4
ACAA2 is a ligand-dependent coactivator for thyroid hormone receptor β1.ACAA2 是甲状腺激素受体 β1 的配体依赖性共激活因子。
Biochem Biophys Res Commun. 2021 Oct 22;576:15-21. doi: 10.1016/j.bbrc.2021.08.073. Epub 2021 Aug 28.
5
Beyond the heterodimer model for mineralocorticoid and glucocorticoid receptor interactions in nuclei and at DNA.超越核内及 DNA 上的盐皮质激素和糖皮质激素受体相互作用的异二聚体模型。
PLoS One. 2020 Jan 10;15(1):e0227520. doi: 10.1371/journal.pone.0227520. eCollection 2020.
6
A novel gene expression analytics-based approach to structure aided design of rexinoids for development as next-generation cancer therapeutics.一种基于新型基因表达分析的方法，用于结构辅助设计类视黄醇X受体激动剂，以开发成为下一代癌症治疗药物。
Steroids. 2018 Jul;135:36-49. doi: 10.1016/j.steroids.2018.04.009. Epub 2018 Apr 26.
7
Analysis of differential secondary effects of novel rexinoids: select rexinoid X receptor ligands demonstrate differentiated side effect profiles.新型视黄醇 X 受体配体的差异次要作用分析：选择视黄醇 X 受体配体表现出不同的副作用特征。
Pharmacol Res Perspect. 2015 Mar;3(2):e00122. doi: 10.1002/prp2.122. Epub 2015 Mar 16.
8
RXR agonist modulates TR: corepressor dissociation upon 9-cis retinoic acid treatment.视黄酸X受体激动剂在9-顺式视黄酸处理后调节甲状腺激素受体：共抑制因子解离。
Mol Endocrinol. 2015 Feb;29(2):258-73. doi: 10.1210/me.2014-1251. Epub 2014 Dec 26.
9
Modeling, synthesis, and biological evaluation of potential retinoid X receptor (RXR) selective agonists: novel analogues of 4-[1-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)ethynyl]benzoic acid (bexarotene) and (E)-3-(3-(1,2,3,4-tetrahydro-1,1,4,4,6-pentamethylnaphthalen-7-yl)-4-hydroxyphenyl)acrylic acid (CD3254).潜在视黄醇 X 受体（RXR）选择性激动剂的建模、合成和生物学评价：4-[1-(3,5,5,8,8-五甲基-5,6,7,8-四氢-2-萘基)乙炔基]苯甲酸（贝沙罗汀）和(E)-3-(3-(1,2,3,4-四氢-1,1,4,4,6-五甲基萘-7-基)-4-羟基苯基)丙烯酸（CD3254）的新型类似物。
J Med Chem. 2013 Nov 14;56(21):8432-54. doi: 10.1021/jm4008517. Epub 2013 Nov 1.
10
The trifunctional protein mediates thyroid hormone receptor-dependent stimulation of mitochondria metabolism.三功能蛋白介导甲状腺激素受体依赖性的线粒体代谢刺激作用。
Mol Endocrinol. 2012 Jul;26(7):1117-28. doi: 10.1210/me.2011-1348. Epub 2012 May 8.
Proc Natl Acad Sci U S A. 1984 May;81(9):2626-30. doi: 10.1073/pnas.81.9.2626.
4
Vitamin A and retinoids: from nutrition to pharmacotherapy in dermatology and oncology.维生素A与类视黄醇：从营养学应用到皮肤病学与肿瘤学的药物治疗
Lancet. 1983 Apr 16;1(8329):860-3. doi: 10.1016/s0140-6736(83)91394-6.
5
A novel thyroid hormone receptor encoded by a cDNA clone from a human testis library.一种由来自人睾丸文库的cDNA克隆编码的新型甲状腺激素受体。
Science. 1987 Nov 6;238(4828):788-91. doi: 10.1126/science.3672126.
6
Retinoids as preventive and therapeutic anticancer agents (Part I).维甲酸作为预防和治疗癌症的药物（第一部分）。
Cancer Treat Rep. 1987 Apr;71(4):391-405.
7
Prevention of skin cancer in xeroderma pigmentosum with the use of oral isotretinoin.口服异维甲酸预防着色性干皮病中的皮肤癌。
N Engl J Med. 1988 Jun 23;318(25):1633-7. doi: 10.1056/NEJM198806233182501.
8
Use of all-trans retinoic acid in the treatment of acute promyelocytic leukemia.全反式维甲酸在急性早幼粒细胞白血病治疗中的应用。
Blood. 1988 Aug;72(2):567-72.
9
Gene regulation by steroid hormones.类固醇激素对基因的调控。
Cell. 1989 Feb 10;56(3):335-44. doi: 10.1016/0092-8674(89)90237-7.
10
A domain containing leucine-zipper-like motifs mediate novel in vivo interactions between the thyroid hormone and retinoic acid receptors.一个包含亮氨酸拉链样基序的结构域介导甲状腺激素受体与视黄酸受体之间新的体内相互作用。
Mol Endocrinol. 1989 Oct;3(10):1610-26. doi: 10.1210/mend-3-10-1610.