Palmitoylation-dependent Estrogen Receptor α Membrane Localization: Regulation by 17β-Estradiol

Molecular Biology of the Cell - Tập 16 Số 1 - Trang 231-237 - 2005
Filippo Acconcia1, Paolo Ascenzi1,2,3, Alessio Bocedi4,3, Enzo Spisni5, Vittorio Tomasi5, A Trentalance1, Paolo Visca1,3, Maria Marino1
1Department of Biology, University “Roma Tre,” I-00146 Rome, Italy
2Interdepartmental Laboratory for Electron Microscopy, University Roma Tre, I-00146 Rome, Italy
3National Institute for Infectious Diseases Istituto di Ricovero e Cura a Carattere Scientifico Lazzaro Spallanzani, I-00149 Rome, Italy
4Department of Chemistry, Chemical Engineering, and Materials, University of L'Aquila, I-67100 L'Aquila, Italy
5Department of Experimental Biology, University of Bologna, I-40126 Bologna, Italy

Tóm tắt

A fraction of the nuclear estrogen receptor α (ERα) is localized to the plasma membrane region of 17β-estradiol (E2) target cells. We previously reported that ERα is a palmitoylated protein. To gain insight into the molecular mechanism of ERα residence at the plasma membrane, we tested both the role of palmitoylation and the impact of E2 stimulation on ERα membrane localization. The cancer cell lines expressing transfected or endogenous human ERα (HeLa and HepG2, respectively) or the ERα nonpalmitoylable Cys447Ala mutant transfected in HeLa cells were used as experimental models. We found that palmitoylation of ERα enacts ERα 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 D1 promoter activity, DNA synthesis). Moreover, E2 reduces both ERα palmitoylation and its interaction with caveolin-1, in a time- and dose-dependent manner. These data point to the physiological role of ERα palmitoylation in the receptor localization to the cell membrane and in the regulation of the E2-induced cell proliferation.

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Molecular Biology of the Cell

Tập 16 Số 1

231-237

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