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细胞周期蛋白A/细胞周期蛋白依赖性激酶2复合物对雌激素受体转录增强的调控。

Regulation of estrogen receptor transcriptional enhancement by the cyclin A/Cdk2 complex.

作者信息

Trowbridge J M, Rogatsky I, Garabedian M J

机构信息

Department of Microbiology and The Kaplan Cancer Center, New York University Medical Center, New York, NY 10016, USA.

出版信息

Proc Natl Acad Sci U S A. 1997 Sep 16;94(19):10132-7. doi: 10.1073/pnas.94.19.10132.

Abstract

We have found that ectopic expression of cyclin A increases hormone-dependent and hormone-independent transcriptional activation by the estrogen receptor in vivo in a number of cell lines, including HeLa cells, U-2 OS osteosarcoma cells and Hs 578Bst breast epithelial cells. This effect can be further enhanced in HeLa cells by the concurrent expression of the cyclin-dependent kinase activator, cyclin H, and cdk7, and abolished by expression of the cdk inhibitor, p27(KIP1), or by the expression of a dominant negative catalytically inactive cdk2 mutant. ER is phosphorylated between amino acids 82 and 121 in vitro by the cyclin A/cdk2 complex and incorporation of phosphate into ER is stimulated by ectopic expression of cyclin A in vivo. Together, these results strongly suggest a direct role for the cyclin A/cdk2 complex in phosphorylating ER and regulating its transcriptional activity.

摘要

我们发现在多种细胞系中,包括HeLa细胞、U-2 OS骨肉瘤细胞和Hs 578Bst乳腺上皮细胞,细胞周期蛋白A的异位表达在体内可增加雌激素受体依赖激素和不依赖激素的转录激活。在HeLa细胞中,通过同时表达细胞周期蛋白依赖性激酶激活剂细胞周期蛋白H和cdk7,这种效应可进一步增强;而通过表达cdk抑制剂p27(KIP1),或表达显性负性催化失活的cdk2突变体,这种效应则会被消除。在体外,细胞周期蛋白A/cdk2复合物可使雌激素受体在氨基酸82至121之间发生磷酸化,并且在体内通过细胞周期蛋白A的异位表达可刺激雌激素受体掺入磷酸。这些结果共同强烈表明细胞周期蛋白A/cdk2复合物在使雌激素受体磷酸化并调节其转录活性中起直接作用。

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