核受体、RXR 和大爆炸。
Nuclear Receptors, RXR, and the Big Bang.
机构信息
Howard Hughes Medical Institute; The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.
Howard Hughes Medical Institute; The Department of Pharmacology, University of Texas Southwestern Medical Center, 6001 Forest Park Road, Dallas, TX 75390, USA.
出版信息
Cell. 2014 Mar 27;157(1):255-66. doi: 10.1016/j.cell.2014.03.012.
Abstract
Isolation of genes encoding the receptors for steroids, retinoids, vitamin D, and thyroid hormone and their structural and functional analysis revealed an evolutionarily conserved template for nuclear hormone receptors. This discovery sparked identification of numerous genes encoding related proteins, termed orphan receptors. Characterization of these orphan receptors and, in particular, of the retinoid X receptor (RXR) positioned nuclear receptors at the epicenter of the "Big Bang" of molecular endocrinology. This Review provides a personal perspective on nuclear receptors and explores their integrated and coordinated signaling networks that are essential for multicellular life, highlighting the RXR heterodimer and its associated ligands and transcriptional mechanism.
摘要
基因编码的甾体激素、维甲酸、维生素 D 和甲状腺激素受体的分离及其结构和功能分析揭示了核激素受体的一个进化保守模板。这一发现引发了对许多编码相关蛋白的基因的鉴定，这些蛋白被称为孤儿受体。这些孤儿受体的特征，特别是视黄酸 X 受体（RXR）的特征，将核受体置于分子内分泌学“大爆炸”的中心。本综述提供了核受体的个人观点，并探讨了它们的整合和协调的信号网络，这对多细胞生命是必不可少的，强调了 RXR 异二聚体及其相关配体和转录机制。
相似文献
1
Nuclear Receptors, RXR, and the Big Bang.核受体、RXR 和大爆炸。
Cell. 2014 Mar 27;157(1):255-66. doi: 10.1016/j.cell.2014.03.012.
2
Physical and functional interactions between liver X receptor/retinoid X receptor and Sp1 modulate the transcriptional induction of the human ATP binding cassette transporter A1 gene by oxysterols and retinoids.肝脏X受体/视黄酸X受体与Sp1之间的物理和功能相互作用通过氧化甾醇和类视黄醇调节人ATP结合盒转运蛋白A1基因的转录诱导。
Biochemistry. 2007 Oct 16;46(41):11473-83. doi: 10.1021/bi700994m. Epub 2007 Sep 22.
3
Alternative retinoid X receptor (RXR) ligands.替代视黄醇 X 受体 (RXR) 配体。
Mol Cell Endocrinol. 2019 Jul 1;491:110436. doi: 10.1016/j.mce.2019.04.016. Epub 2019 Apr 23.
4
Selective allosteric ligand activation of the retinoid X receptor heterodimers of NGFI-B and Nurr1.神经生长因子诱导蛋白B（NGFI-B）和核受体相关因子1（Nurr1）的类视黄醇X受体异二聚体的选择性变构配体激活
Biochem Pharmacol. 2005 Dec 19;71(1-2):98-107. doi: 10.1016/j.bcp.2005.10.017. Epub 2005 Nov 10.
5
LXR, a nuclear receptor that defines a distinct retinoid response pathway.肝X受体（LXR）是一种核受体，它定义了一条独特的视黄酸反应途径。
Genes Dev. 1995 May 1;9(9):1033-45. doi: 10.1101/gad.9.9.1033.
6
Thyroid hormone and thyroid hormone nuclear receptors: History and present state of art.甲状腺激素和甲状腺激素核受体：历史与现状。
Endocr Regul. 2021 May 21;55(2):103-119. doi: 10.2478/enr-2021-0012.
7
8
A regulatory role for RIP140 in nuclear receptor activation.RIP140在核受体激活中的调控作用。
Mol Endocrinol. 1998 Jun;12(6):864-81. doi: 10.1210/mend.12.6.0123.
9
A novel orphan receptor specific for a subset of thyroid hormone-responsive elements and its interaction with the retinoid/thyroid hormone receptor subfamily.一种对甲状腺激素反应元件的一个子集具有特异性的新型孤儿受体及其与视黄酸/甲状腺激素受体亚家族的相互作用。
Mol Cell Biol. 1994 Oct;14(10):7025-35. doi: 10.1128/mcb.14.10.7025-7035.1994.
10
Modulation of RXR function through ligand design.通过配体设计对视黄醇X受体（RXR）功能进行调节。
Biochim Biophys Acta. 2012 Jan;1821(1):57-69. doi: 10.1016/j.bbalip.2011.04.003. Epub 2011 Apr 16.
引用本文的文献
1
Anti-DNA Damage Mechanisms and the Role of Carotenoids, Vitamin A, and Its Derivatives.抗DNA损伤机制以及类胡萝卜素、维生素A及其衍生物的作用。
Nutrients. 2025 Aug 22;17(17):2721. doi: 10.3390/nu17172721.
2
Engineering strategies of sequential drug delivery systems for combination tumor immunotherapy.用于联合肿瘤免疫治疗的序贯给药系统的工程策略。
Acta Pharm Sin B. 2025 Aug;15(8):3951-3977. doi: 10.1016/j.apsb.2025.05.039. Epub 2025 Jun 6.
3
Mechanisms and Therapeutic Advances of PXR in Metabolic Diseases and Cancer.孕烷X受体在代谢性疾病和癌症中的作用机制及治疗进展
Int J Mol Sci. 2025 Aug 20;26(16):8029. doi: 10.3390/ijms26168029.
4
Retinoid X receptor γ interacts with peroxisome proliferator-activated receptor-γ to promote browning during adipose tissue differentiation.维甲酸X受体γ与过氧化物酶体增殖物激活受体γ相互作用，在脂肪组织分化过程中促进褐色化。
Adipocyte. 2025 Dec;14(1):2548780. doi: 10.1080/21623945.2025.2548780. Epub 2025 Aug 25.
5
Isoform differences drive functional diversity of NHR-49.亚型差异驱动NHR-49的功能多样性。
MicroPubl Biol. 2025 Aug 1;2025. doi: 10.17912/micropub.biology.001655. eCollection 2025.
6
Fragment-based discovery of dual ligand pharmacophores for lipid-sensing transcription factors for designed polypharmacology.基于片段的脂质感应转录因子双配体药效团发现用于设计多药理学
RSC Med Chem. 2025 Jul 23. doi: 10.1039/d5md00531k.
7
FXR crosstalk with other nuclear receptors.法尼酯X受体（FXR）与其他核受体的相互作用。
J Physiol Biochem. 2025 Aug 12. doi: 10.1007/s13105-025-01118-2.
8
Cluefish: mining the dark matter of transcriptional data series with over-representation analysis enhanced by aggregated biological prior knowledge.线索鱼：利用聚合生物学先验知识增强的过度表达分析挖掘转录数据系列的暗物质。
NAR Genom Bioinform. 2025 Jul 30;7(3):lqaf103. doi: 10.1093/nargab/lqaf103. eCollection 2025 Sep.
9
Vitamin A5: Evidence, Definitions, Gaps, and Future Directions.维生素A5：证据、定义、差距及未来方向。
Nutrients. 2025 Jul 14;17(14):2317. doi: 10.3390/nu17142317.
10
RXR modulates hepatic stellate cell activation and liver fibrosis by targeting CaMKK-AMPK axis.视黄酸X受体（RXR）通过靶向钙调蛋白激酶激酶（CaMKK）-腺苷酸活化蛋白激酶（AMPK）轴来调节肝星状细胞活化和肝纤维化。
Acta Pharm Sin B. 2025 Jul;15(7):3611-3631. doi: 10.1016/j.apsb.2025.05.023. Epub 2025 May 26.
本文引用的文献
1
Structure of the retinoid X receptor α-liver X receptor β (RXRα-LXRβ) heterodimer on DNA.视黄醇 X 受体 α-肝 X 受体 β（RXRα-LXRβ）异二聚体在 DNA 上的结构。
Nat Struct Mol Biol. 2014 Mar;21(3):277-81. doi: 10.1038/nsmb.2778. Epub 2014 Feb 23.
2
PPAR-α as a key nutritional and environmental sensor for metabolic adaptation.过氧化物酶体增殖物激活受体-α作为代谢适应的关键营养和环境传感器。
Adv Nutr. 2013 Jul 1;4(4):439-52. doi: 10.3945/an.113.003798.
3
Hormone-regulated transcriptomes: lessons learned from estrogen signaling pathways in breast cancer cells.激素调控的转录组学：从乳腺癌细胞中的雌激素信号通路中得到的启示。
Mol Cell Endocrinol. 2014 Jan 25;382(1):652-664. doi: 10.1016/j.mce.2013.06.021. Epub 2013 Jun 28.
4
Rev-Erbs repress macrophage gene expression by inhibiting enhancer-directed transcription.REV-ERBs 通过抑制增强子指导的转录来抑制巨噬细胞基因表达。
Nature. 2013 Jun 27;498(7455):511-5. doi: 10.1038/nature12209. Epub 2013 Jun 2.
5
Nuclear receptor/microRNA circuitry links muscle fiber type to energy metabolism.核受体/微小 RNA 回路将肌纤维类型与能量代谢联系起来。
J Clin Invest. 2013 Jun;123(6):2564-75. doi: 10.1172/JCI67652. Epub 2013 May 8.
6
A vitamin D receptor/SMAD genomic circuit gates hepatic fibrotic response.维生素 D 受体/SMAD 基因组回路调控肝纤维化反应。
Cell. 2013 Apr 25;153(3):601-13. doi: 10.1016/j.cell.2013.03.028.
7
Pleiotropic roles of bile acids in metabolism.胆汁酸在代谢中的多效性作用。
Cell Metab. 2013 May 7;17(5):657-69. doi: 10.1016/j.cmet.2013.03.013. Epub 2013 Apr 18.
8
Complex genomic interactions in the dynamic regulation of transcription by the glucocorticoid receptor.糖皮质激素受体转录动态调控中的复杂基因组相互作用。
Mol Cell Endocrinol. 2013 Nov 5;380(1-2):16-24. doi: 10.1016/j.mce.2013.03.002. Epub 2013 Mar 14.
9
The long-range interaction landscape of gene promoters.基因启动子的远程相互作用景观。
Nature. 2012 Sep 6;489(7414):109-13. doi: 10.1038/nature11279.
10
Minireview: nuclear receptor and coregulator proteomics--2012 and beyond.综述：核受体与共调节因子蛋白质组学——2012年及以后
Mol Endocrinol. 2012 Oct;26(10):1646-50. doi: 10.1210/me.2012-1114. Epub 2012 Jun 28.
Zotero 插件