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孕激素受体:亚型与抗激素作用

Progestin receptors: isoforms and antihormone action.

作者信息

Gronemeyer H, Meyer M E, Bocquel M T, Kastner P, Turcotte B, Chambon P

机构信息

Laboratoire de Génétique Moléculaire des Eucaryotes du CNRS, Institut de Chimie Biologique, Faculté de Médecine, Strasbourg, France.

出版信息

J Steroid Biochem Mol Biol. 1991;40(1-3):271-8. doi: 10.1016/0960-0760(91)90192-8.

DOI:10.1016/0960-0760(91)90192-8
PMID:1958531
Abstract

We present evidence that the two isoforms of A and B of the chicken (cPR) and human progesterone receptor (hPR) originate from two different mRNA populations. One of these encodes the isoforms A which originate by initiation of translation at an in-frame AUG found 127 (cPR) and 165 (hPR) codons downstream of the AUG which gives rise to the isoforms B. Two estrogen-inducible hPR promoters were identified which are responsible for the generation of these two classes of transcripts. Characterization of the cPR promoter suggested the possible existence of cell-type and isoform-specific auto-regulation of cPR transcription and provided evidence that estrogen-induction of cPR expression occurs at a post-transcriptional level. Finally, we demonstrate promoter-specific transcriptional activation by the hPR isoforms A and B, and we discuss the mechanism of action of the anti-progestin RU486.

摘要

我们提供的证据表明,鸡孕酮受体(cPR)和人孕酮受体(hPR)的A和B两种亚型源自两个不同的mRNA群体。其中一个群体编码A亚型,它是通过在位于产生B亚型的AUG下游127个(cPR)和165个(hPR)密码子处的框内AUG起始翻译而产生的。鉴定出了两个雌激素诱导型hPR启动子,它们负责产生这两类转录本。cPR启动子的特性表明可能存在cPR转录的细胞类型和亚型特异性自动调节,并提供了证据表明cPR表达的雌激素诱导发生在转录后水平。最后,我们证明了hPR A和B亚型的启动子特异性转录激活,并讨论了抗孕激素RU486的作用机制。

相似文献

1
Progestin receptors: isoforms and antihormone action.孕激素受体:亚型与抗激素作用
J Steroid Biochem Mol Biol. 1991;40(1-3):271-8. doi: 10.1016/0960-0760(91)90192-8.
2
Transient expression of human and chicken progesterone receptors does not support alternative translational initiation from a single mRNA as the mechanism generating two receptor isoforms.人和鸡孕酮受体的瞬时表达并不支持从单个mRNA通过替代翻译起始作为产生两种受体亚型的机制。
J Biol Chem. 1990 Jul 25;265(21):12163-7.
3
Agonistic and antagonistic activities of RU486 on the functions of the human progesterone receptor.RU486对人孕酮受体功能的激动和拮抗活性。
EMBO J. 1990 Dec;9(12):3923-32. doi: 10.1002/j.1460-2075.1990.tb07613.x.
4
Two distinct estrogen-regulated promoters generate transcripts encoding the two functionally different human progesterone receptor forms A and B.两个不同的雌激素调节启动子产生编码两种功能不同的人孕酮受体A和B形式的转录本。
EMBO J. 1990 May;9(5):1603-14. doi: 10.1002/j.1460-2075.1990.tb08280.x.
5
A single amino acid that determines the sensitivity of progesterone receptors to RU486.一个决定孕酮受体对RU486敏感性的单一氨基酸。
Science. 1992 Jan 10;255(5041):206-9. doi: 10.1126/science.1372753.
6
Mapping and characterization of the functional domains responsible for the differential activity of the A and B isoforms of the human progesterone receptor.负责人类孕酮受体A和B亚型差异活性的功能域的定位与表征
J Biol Chem. 1997 Dec 26;272(52):32889-900. doi: 10.1074/jbc.272.52.32889.
7
Control of transcription of the chicken progesterone receptor gene. In vitro and in vivo studies.鸡孕激素受体基因转录的调控。体外和体内研究。
J Biol Chem. 1991 Feb 5;266(4):2582-9.
8
An amino-terminal truncated progesterone receptor isoform, PRc, enhances progestin-induced transcriptional activity.一种氨基末端截短的孕激素受体亚型PRc可增强孕激素诱导的转录活性。
Mol Endocrinol. 1996 Nov;10(11):1379-87. doi: 10.1210/mend.10.11.8923464.
9
Characterization of multiple mRNAs originating from the chicken progesterone receptor gene. Evidence for a specific transcript encoding form A.源自鸡孕酮受体基因的多个mRNA的特性分析。编码A形式的特定转录本的证据。
J Biol Chem. 1990 Mar 5;265(7):3967-74.
10
Human progesterone receptor A form is a cell- and promoter-specific repressor of human progesterone receptor B function.人孕激素受体A亚型是一种对人孕激素受体B功能具有细胞和启动子特异性的抑制因子。
Mol Endocrinol. 1993 Oct;7(10):1244-55. doi: 10.1210/mend.7.10.8264658.

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