title: Clathrin Heavy Chain Interacts With Estrogen Receptor α and Modulates 17β-Estradiol Signaling.
abstract: 17β-estradiol (E2)-induced signaling and control of estrogen receptor (ER)α degradation both play a major role in breast cancer cell proliferation. We recently reported the involvement of lysosomal function in both E2-dependent ERα breakdown and E2-induced cell proliferation and thus hypothesized a role for endocytic proteins in ERα signaling. An small interfering RNA screen identified proteins that regulate intracellular endocytic traffic and whose silencing alters E2-induced ERα degradation. One such protein was the clathrin heavy chain (CHC), whose role in E2:ERα signaling to cell proliferation is unknown. Here, we show that CHC physically interacts with ERα in the cytoplasm of breast cancer cells and regulates E2-induced cell proliferation. Surprisingly, the CHC:ERα interaction is required to sustain E2 signaling but is dispensable for ERα degradation. Our data also demonstrate that many membrane trafficking proteins contribute to the regulation of ERα degradation, thus unraveling the contribution of endocytic proteins in E2:ERα signaling.
authors: Department of Sciences (P.T., V.P., M.M., F.A.), Section Biomedical Sciences and Technology, University Roma Tre, I-00146, Rome, Italy; and Division of Refractory Cancer Research (M.E.), National Cancer Center Research Institute, Chuo-ku, Tokyo 104-0045, Japan.
authors: Pierangela
authors: P
authors: Totta
authors: Valeria
authors: V
authors: Pesiri
authors: Masato
authors: M
authors: Enari
authors: Maria
authors: M
authors: Marino
authors: Filippo
authors: F
authors: Acconcia
mesh_terms: D049109:Cell Proliferation; D033922:Clathrin Heavy Chains / Q000378:metabolism*; D004705:Endocytosis; D004958:Estradiol / Q000502:physiology*; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D006801:Humans; D061986:MCF-7 Cells; D019308:Palmitic Acid / Q000378:metabolism; D011485:Protein Binding; D025941:Protein Interaction Mapping; D011499:Protein Processing, Post-Translational; D059748:Proteolysis; D017526:Receptor, IGF Type 1 / Q000378:metabolism; D015398:Signal Transduction
chemical_list: C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D033922:Clathrin Heavy Chains; D019308:Palmitic Acid; D004958:Estradiol; D017526:Receptor, IGF Type 1