中国医学科学院学报

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中国医学科学院学报

中国医学科学院学报 ›› 2011, Vol. 33 ›› Issue (2): 156-161.doi: 10.3881/j.issn.1000-503X.2011.02.012

• 论著 • 上一篇    下一篇

胰岛素样生长因子结合蛋白3与甲状腺激素受体α1的相互作用及其对甲状腺激素应答性基因转录的调节

裘 佳,马晓骊,王 欣,陈 虹,黄秉仁   

  1. 中国医学科学院 北京协和医学院 基础医学研究所医学分子生物学国家重点实验室, 北京 100005
  • 收稿日期:2010-07-23 出版日期:2011-04-10 发布日期:2011-04-10
  • 通讯作者: 黄秉仁 电话:010-65228797,陈虹 电话:010-65296980 E-mail:huangbr@public.bta.net.cn

Insulin-like Growth Factor Binding Protein-3 Interacts with the ThyroidHormone Receptor α1 and Modulates Transcription of Thyroid Hormone Responsive Gene

 QIU   Jia, MA  Xiao-Li, WANG   Xin, CHEN   Hong, HUANG  Bing-Ren   

  1. National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, CAMS and PUMC,Beijing 100005, China
  • Received:2010-07-23 Online:2011-04-10 Published:2011-04-10
  • Contact: HUANG Bing-ren Tel:010-65228797,CHEN Hong Tel:010-65296980 E-mail:huangbr@public.bta.net.cn

摘要: 目的 探讨胰岛素样生长因子结合蛋白-3(IGFBP-3)与甲状腺激素受体α1(TRα1)之间的相互作用,及其对甲状腺激素应答性基因转录作用的调节。方法 采用谷胱甘肽-S-转移酶拉下实验、免疫共沉淀以及荧光共振能量转移实验检测IGFBP-3与TRα1之间的相互作用;激光共聚焦显微镜观察两种蛋白在细胞中的分布;采用双萤光素酶实验检测过表达IGFBP-3对甲状腺素T3激活的生长激素启动子的影响。 结果 谷胱甘肽-S-转移酶拉下实验、免疫共沉淀以及荧光共振能量转移实验结果证明IGFBP-3与TRα1在体内和体外都可以相互作用,激光共聚焦显微镜观察IGFBP-3 和 TRα1可以共定位于HEK-293细胞的细胞核。通过双萤光素酶实验检测到过表达IGFBP-3可以抑制甲状腺激素对生长激素启动子的激活作用(P<0.01)。结论 IGFBP-3通过与TRα1相互作用抑制甲状腺激素应答性基因的转录,为IGFBP-3在核内发挥胰岛素样生长因子非依赖的作用提供了新的实验依据。

关键词: 胰岛素样生长因子结合蛋白-3, 甲状腺激素受体α1, 三碘甲状腺原氨酸, 生长激素启动子

Abstract: Objective To study the interaction between insulin-like growth factor binding protein-3 (IGFBP-3) and thyroid hormone receptor α1 (TRα1) and the modulatory effect of IGFBP-3 on transcription of the thyroid hormone responsive gene. Methods The interaction between IGFBP-3 and TRα1 was detected with glutathione-S-transferase pull-down method, co-immunoprecipitation, fluorescence resonance energy transfer test. The cellular distribution of these two proteins was observed by confocal laser scanning microscopy. The effect of IGFBP-3 on the growth hormone promoter activity stimulated by triiodothyronine (T3) was determined by dual-luciferase reporter assay. Results IGFBP-3 interacted with TRα1 both in vivo and in vitro. IGFBP-3 and TRα1 were shown to co-localize in the nucleus of HEK-293 cells. The overexpressed IGFBP-3 inhibited the growth hormone promoter activity stimulated by T3 (P<0.01). Conclusions IGFBP-3 interacts with TRα1 and inhibits T3 responsive gene transcription. This finding further confirms the insulin-like growth factor-independent role of IGFBP-3 in the nucleus.

Key words: insulin-like growth factor binding protein-3, thyroid hormone receptor α1, triiodothyronine, growth hormone promoter

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