Palmitoylation-dependent estrogen receptor α membrane localization:: Regulation by 17β-estradiol
Palmitoylation-dependent estrogen receptor α membrane localization:: Regulation by 17β-estradiol
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DOI：
10.1091/mbc.e04-07-0547
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发表时间：
2005-01-01
影响因子：
3.3
通讯作者：
Marino, M
中科院分区：
文献类型：
--
作者：
Acconcia, F;Ascenzi, P;Marino, M
雌激素受体α的一部分定位于17β-雌二醇(E2)靶细胞的质膜区域。我们以前报道过ERpha是一种棕榈酰化的蛋白质。为了深入了解ERpha滞留在质膜上的分子机制，我们测试了棕榈酰化作用和E2刺激对ERpha膜定位的影响。以表达转染型或内源性人ERa(分别为HeLa和HepG2)的癌细胞系和转染人ERpha非棕榈酰化Cys447Ala突变体的HeLa细胞为实验模型。我们发现，ERα的棕榈酰化使ERα与质膜结合，与膜蛋白Caveolin-1相互作用，以及非基因组活动，包括激活信号通路和细胞增殖(即ERK和AKT激活，Cyclin D-1启动子活性，DNA合成)。此外，E2以时间和剂量依赖的方式减少ERpha棕榈酰化及其与小窝蛋白-1的相互作用。这些数据表明，ERpha棕榈酰化在受体定位到细胞膜和调控E2诱导的细胞增殖中起着生理作用。
A fraction of the nuclear estrogen receptor a (ERalpha) is localized to the plasma membrane region of 17beta-estradiol (E2) target cells. We previously reported that ERalpha is a palmitoylated protein. To gain insight into the molecular mechanism of ERalpha residence at the plasma membrane, we tested both the role of palmitoylation and the impact of E2 stimulation on ERalpha membrane localization. The cancer cell lines expressing transfected or endogenous human ERalpha (HeLa and HepG2, respectively) or the ERalpha nonpalmitoylable Cys447Ala mutant transfected in HeLa cells were used as experimental models. We found that palmitoylation of ERalpha enacts ERalpha association with the plasma membrane, interaction with the membrane protein caveolin-1, and nongenomic activities, including activation of signaling pathways and cell proliferation (i.e., ERK and AKT activation, cyclin D-1 promoter activity, DNA synthesis). Moreover, E2 reduces both ERalpha palmitoylation and its interaction with caveolin-1, in a time- and dose-dependent manner. These data point to the physiological role of ERalpha palmitoylation in the receptor localization to the cell membrane and in the regulation of the E2-induced cell proliferation.