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超活性雌激素受体。基因表达的强效激活剂。

Superactive estrogen receptors. Potent activators of gene expression.

作者信息

Elliston J F, Tsai S Y, O'Malley B W, Tsai M J

机构信息

Department of Cell Biology, Baylor College of Medicine, Houston, Texas 77030.

出版信息

J Biol Chem. 1990 Jul 15;265(20):11517-21.

PMID:2164005
Abstract

We have constructed novel chimeric receptors consisting of the activation region of the herpes simplex virus transcription factor VP16 inserted into the amino-terminal region of the human estrogen receptor containing or lacking the hormone-binding region. By gene transfer into mammalian cells, these chimeric receptors behave in a hormone-dependent or hormone-independent manner, respectively, and are more efficient activators of gene expression than wild-type estrogen receptor. These studies indicate that a potent activation region from a viral transcription factor can be placed under hormonal control when introduced into a steroid receptor molecule and can enhance the receptor's potency (approximately 10-fold) in activating specific gene expression. It is likely that such chimeric molecules could be designed to increase selected target gene responses to any intracellular receptor in the course of cellular transfection, transformation, or transgenic animal experiments.

摘要

我们构建了新型嵌合受体,其由插入到人雌激素受体氨基末端区域(含或不含激素结合区域)的单纯疱疹病毒转录因子VP16的激活区域组成。通过基因转移到哺乳动物细胞中,这些嵌合受体分别以激素依赖性或激素非依赖性方式发挥作用,并且比野生型雌激素受体更有效地激活基因表达。这些研究表明,当将病毒转录因子的有效激活区域引入类固醇受体分子时,可以将其置于激素控制之下,并可增强受体激活特定基因表达的能力(约10倍)。很可能可以设计这样的嵌合分子,以在细胞转染、转化或转基因动物实验过程中增加选定靶基因对任何细胞内受体的反应。

相似文献

1
Superactive estrogen receptors. Potent activators of gene expression.超活性雌激素受体。基因表达的强效激活剂。
J Biol Chem. 1990 Jul 15;265(20):11517-21.
2
High efficiency transient expression of eukaryotic genes: use of an HSV-1 immediate early promoter (ICP4).真核基因的高效瞬时表达:使用单纯疱疹病毒1型立即早期启动子(ICP4)。
Biotechniques. 1990 Aug;9(2):168-73.
3
Characterization of a temperature-sensitive mutation in the hormone binding domain of the human estrogen receptor. Studies in cell extracts and intact cells and their implications for hormone-dependent transcriptional activation.
J Biol Chem. 1992 May 15;267(14):9868-73.
4
The RR1 gene of herpes simplex virus type 1 is uniquely trans activated by ICP0 during infection.单纯疱疹病毒1型的RR1基因在感染期间由ICP0独特地反式激活。
J Virol. 1993 Oct;67(10):6125-35. doi: 10.1128/JVI.67.10.6125-6135.1993.
5
The human estrogen receptor has two independent nonacidic transcriptional activation functions.人类雌激素受体具有两种独立的非酸性转录激活功能。
Cell. 1989 Nov 3;59(3):477-87. doi: 10.1016/0092-8674(89)90031-7.
6
Different regions of the estrogen receptor are required for synergistic action with the glucocorticoid and progesterone receptors.雌激素受体的不同区域对于与糖皮质激素受体和孕激素受体的协同作用是必需的。
Mol Cell Biol. 1989 Dec;9(12):5324-30. doi: 10.1128/mcb.9.12.5324-5330.1989.
7
Enhanced infectivity of herpes simplex virus type 1 viral DNA in a cell line expressing the trans-inducing factor Vmw65.在表达反式诱导因子Vmw65的细胞系中,单纯疱疹病毒1型病毒DNA的感染性增强。
J Virol. 1990 Mar;64(3):984-91. doi: 10.1128/JVI.64.3.984-991.1990.
8
Characterization of a potent varicella-zoster virus-encoded trans-repressor.一种强效水痘带状疱疹病毒编码的反式阻遏物的特性分析
J Virol. 1991 Oct;65(10):5289-96. doi: 10.1128/JVI.65.10.5289-5296.1991.
9
Sequence, function, and regulation of the Vmw65 gene of herpes simplex virus type 2.单纯疱疹病毒2型Vmw65基因的序列、功能及调控
J Virol. 1991 Dec;65(12):6705-13. doi: 10.1128/JVI.65.12.6705-6713.1991.
10
Activity of the simian virus 40 early promoter-enhancer in herpes simplex virus type 1 vectors is dependent on its position, the infected cell type, and the presence of Vmw175.猿猴病毒40早期启动子-增强子在1型单纯疱疹病毒载体中的活性取决于其位置、感染的细胞类型以及Vmw175的存在。
J Virol. 1991 Dec;65(12):6900-12. doi: 10.1128/JVI.65.12.6900-6912.1991.

引用本文的文献

1
Influence of the v-Myb transactivation domain on the oncoprotein's transformation specificity.v-Myb反式激活结构域对癌蛋白转化特异性的影响。
EMBO J. 1993 Apr;12(4):1333-41. doi: 10.1002/j.1460-2075.1993.tb05778.x.
2
Estradiol-inducible squelching and cell growth arrest by a chimeric VP16-estrogen receptor expressed in Saccharomyces cerevisiae: suppression by an allele of PDR1.在酿酒酵母中表达的嵌合VP16-雌激素受体介导的雌二醇诱导的抑制作用和细胞生长停滞:PDR1等位基因的抑制作用
Mol Cell Biol. 1993 Jan;13(1):462-72. doi: 10.1128/mcb.13.1.462-472.1993.
3
Antiestrogen can establish nonproductive receptor complexes and alter chromatin structure at target enhancers.
抗雌激素可形成无活性的受体复合物,并改变靶增强子处的染色质结构。
Proc Natl Acad Sci U S A. 1991 Apr 15;88(8):3125-9. doi: 10.1073/pnas.88.8.3125.
4
In situ distinction between steroid receptor binding and transactivation at a target gene.靶基因处类固醇受体结合与反式激活的原位区分
Mol Cell Biol. 1991 Sep;11(9):4350-5. doi: 10.1128/mcb.11.9.4350-4355.1991.
5
Identification of a negative regulatory function for steroid receptors.类固醇受体负调控功能的鉴定。
Proc Natl Acad Sci U S A. 1992 Nov 15;89(22):10563-7. doi: 10.1073/pnas.89.22.10563.
6
Examination of the DNA-binding ability of estrogen receptor in whole cells: implications for hormone-independent transactivation and the actions of antiestrogens.全细胞中雌激素受体DNA结合能力的检测:对激素非依赖性反式激活及抗雌激素作用的意义
Mol Cell Biol. 1992 Oct;12(10):4531-8. doi: 10.1128/mcb.12.10.4531-4538.1992.