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The co-chaperone XAP2 is required for activation of hypothalamic thyrotropin-releasing hormone transcription in vivo.共伴侣蛋白XAP2是体内下丘脑促甲状腺激素释放激素转录激活所必需的。
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2
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The thyrotropin-releasing hormone gene 1998: cloning, characterization, and transcriptional regulation in the central nervous system, heart, and testis.促甲状腺激素释放激素基因1998：中枢神经系统、心脏和睾丸中的克隆、特性鉴定及转录调控
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The expression of AIP-related molecules in elucidation of cellular pathways in pituitary adenomas.阐明脑垂体腺瘤细胞通路中 AIP 相关分子的表达。
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本文引用的文献

1
Lipid-mediated siRNA delivery down-regulates exogenous gene expression in the mouse brain at picomolar levels.脂质介导的小干扰RNA递送在皮摩尔水平下调小鼠脑中的外源基因表达。
J Gene Med. 2005 Feb;7(2):198-207. doi: 10.1002/jgm.659.
2
Both thyroid hormone receptor (TR)beta 1 and TR beta 2 isoforms contribute to the regulation of hypothalamic thyrotropin-releasing hormone.甲状腺激素受体（TR）β1和TRβ2亚型均参与下丘脑促甲状腺激素释放激素的调节。
Endocrinology. 2004 May;145(5):2337-45. doi: 10.1210/en.2003-1209. Epub 2004 Jan 15.
3
Effects of hyperactive Janus kinase 2 signaling in mammary epithelial cells.乳腺上皮细胞中Janus激酶2信号过度激活的影响。
Biochem Biophys Res Commun. 2002 Aug 9;296(1):139-44. doi: 10.1016/s0006-291x(02)00847-1.
4
Feedback on hypothalamic TRH transcription is dependent on thyroid hormone receptor N terminus.下丘脑促甲状腺激素释放激素转录的反馈取决于甲状腺激素受体的N端。
Mol Endocrinol. 2002 Jul;16(7):1652-66. doi: 10.1210/mend.16.7.0868.
5
Critical role for thyroid hormone receptor beta2 in the regulation of paraventricular thyrotropin-releasing hormone neurons.甲状腺激素受体β2在室旁促甲状腺激素释放激素神经元调节中的关键作用。
J Clin Invest. 2001 Apr;107(8):1017-23. doi: 10.1172/JCI10858.
6
The hsp90 chaperone complex regulates intracellular localization of the dioxin receptor.热休克蛋白90伴侣复合体调节二噁英受体的细胞内定位。
Mol Cell Biol. 2001 Apr;21(7):2594-607. doi: 10.1128/MCB.21.7.2594-2607.2001.
7
The immunophilin-like protein XAP2 regulates ubiquitination and subcellular localization of the dioxin receptor.亲免素样蛋白XAP2调节二噁英受体的泛素化和亚细胞定位。
J Biol Chem. 2000 Dec 29;275(52):41317-24. doi: 10.1074/jbc.M007765200.
8
Characterization of the Ah receptor-associated protein, ARA9.芳烃受体相关蛋白ARA9的特性分析
J Biol Chem. 1998 Dec 11;273(50):33580-7. doi: 10.1074/jbc.273.50.33580.
9
Physiological regulation of hypothalamic TRH transcription in vivo is T3 receptor isoform specific.体内下丘脑促甲状腺激素释放激素转录的生理调节具有甲状腺激素受体亚型特异性。
FASEB J. 1998 Dec;12(15):1755-64. doi: 10.1096/fasebj.12.15.1755.
10
Hepatitis B virus X-associated protein 2 is a subunit of the unliganded aryl hydrocarbon receptor core complex and exhibits transcriptional enhancer activity.乙型肝炎病毒X相关蛋白2是未结合配体的芳烃受体核心复合物的一个亚基，并具有转录增强子活性。
Mol Cell Biol. 1998 Feb;18(2):978-88. doi: 10.1128/MCB.18.2.978.

共伴侣蛋白XAP2是体内下丘脑促甲状腺激素释放激素转录激活所必需的。

The co-chaperone XAP2 is required for activation of hypothalamic thyrotropin-releasing hormone transcription in vivo.

作者信息

Froidevaux Marie-Stéphanie Clerget, Berg Petra, Seugnet Isabelle, Decherf Stéphanie, Becker Nathalie, Sachs Laurent M, Bilesimo Patrice, Nygård Maria, Pongratz Ingemar, Demeneix Barbara A

机构信息

UMR 5166, CNRS/MNHN USM 501, 57 rue Cuvier, Bp 32, Paris Cedex 05, France.

出版信息

EMBO Rep. 2006 Oct;7(10):1035-9. doi: 10.1038/sj.embor.7400778. Epub 2006 Aug 25.

DOI:10.1038/sj.embor.7400778
PMID:16936638
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1618373/
Abstract

Transcriptional control of hypothalamic thyrotropin-releasing hormone (TRH) integrates central regulation of the hypothalamo-hypophyseal-thyroid axis and hence thyroid hormone (triiodothyronine (T(3))) homeostasis. The two beta thyroid hormone receptors, TRbeta1 and TRbeta2, contribute to T(3) feedback on TRH, with TRbeta1 having a more important role in the activation of TRH transcription. How TRbeta1 fulfils its role in activating TRH gene transcription is unknown. By using a yeast two-hybrid screening of a mouse hypothalamic complementary DNA library, we identified a novel partner for TRbeta1, hepatitis virus B X-associated protein 2 (XAP2), a protein first identified as a co-chaperone protein. TR-XAP2 interactions were TR isoform specific, being observed only with TRbeta1, and were enhanced by T(3) both in yeast and mammalian cells. Furthermore, small inhibitory RNA-mediated knockdown of XAP2 in vitro affected the stability of TRbeta1. In vivo, siXAP2 abrogated specifically TRbeta1-mediated (but not TRbeta2) activation of hypothalamic TRH transcription. This study provides the first in vivo demonstration of a regulatory, physiological role for XAP2.

摘要

下丘脑促甲状腺激素释放激素（TRH）的转录调控整合了下丘脑 - 垂体 - 甲状腺轴的中枢调节，从而维持甲状腺激素（三碘甲状腺原氨酸（T(3)））的稳态。两种β甲状腺激素受体，TRβ1和TRβ2，参与T(3)对TRH的反馈调节，其中TRβ1在激活TRH转录方面发挥更重要的作用。TRβ1如何在激活TRH基因转录中发挥作用尚不清楚。通过对小鼠下丘脑互补DNA文库进行酵母双杂交筛选，我们鉴定出TRβ1的一个新伴侣，乙型肝炎病毒X相关蛋白2（XAP2），一种最初被鉴定为共伴侣蛋白的蛋白质。TR - XAP2相互作用具有TR亚型特异性，仅在TRβ1中观察到，并且在酵母和哺乳动物细胞中均被T(3)增强。此外，体外小干扰RNA介导的XAP2敲低影响TRβ1的稳定性。在体内，siXAP2特异性消除了下丘脑TRH转录的TRβ1介导（而非TRβ2介导）的激活。本研究首次在体内证明了XAP2的调节生理作用。