JAB1 interacts with both the progesterone receptor and SRC-1

JAB1 interacts with both the progesterone receptor and SRC-1
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DOI:
10.1074/jbc.275.12.8540
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发表时间:
2000-03-24
影响因子:
4.8
通讯作者:
Loosfelt, H
Loosfelt, H
中科院分区:
生物学2区
文献类型:
--
作者:
Chauchereau, A;Georgiakaki, M;Loosfelt, H

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JAB1(Jun激活域结合蛋白-1)是AP1转录因子的共激活因子。在这里,我们通过酵母和哺乳动物的双杂交分析和下拉实验表明,JAB1还与孕激素受体(PR)和类固醇受体辅活化子1(SRC-1)相互作用,并稳定PR-SRC-1复合体。我们还发现JAB1增强了已知的与SRC-1相关的各种转录因子(核受体、激活蛋白-1和核因子KB)的活性。这在不改变PR或SRC-1浓度的情况下发生。JAB1是一个大型多蛋白复合体的亚基,被称为COP9信号体。后者存在于植物和动物细胞中,已被证明参与了多种细胞机制,包括转录调节、细胞周期控制和磷酸化级联反应。我们现在表明,它也参与了核受体及其辅助激活剂的作用机制。
JAB1 (Jun activation domain-binding protein-1) has previously been described as a coactivator of AP1 transcription factor. We show here, by yeast and mammalian two-hybrid analyses and by pull-down experiments, that JAB1 also interacts with both the progesterone receptor (PR) and the steroid receptor coactivator 1 (SRC-1) and that it stabilizes PR-SRC-1 complexes. We also show that JAB1 potentiates the activity of a variety of transcription factors known to associate with SRC-1 (nuclear receptors, activator protein-1, and nuclear factor KB). This occurs without any modification of PR or SRC-1 concentration. JAB1 is a subunit of a large multiprotein complex that has been called the COP9 signalosome. The latter is present in plant and animal cells and has been shown to be involved in a variety of cellular mechanisms including transcription regulation, cell cycle control, and phosphorylation cascades. We now show that it is also involved in the mechanisms of action of nuclear receptors and of their coactivators.