Open AccessClathrin Heavy Chain Interacts With Estrogen Receptor α and Modulates 17β-Estradiol Signaling
Author(s) -
Pierangela Totta,
Valeria Pesiri,
Masato Enari,
Maria Marino,
Filippo Acconcia
Publication year - 2015
Publication title -
molecular endocrinology
Language(s) - English
Resource type - Journals
eISSN - 1944-9917
pISSN - 0888-8809
DOI - 10.1210/me.2014-1385
Subject(s) - biology , clathrin , estrogen receptor , microbiology and biotechnology , signal transduction , estrogen , estrogen receptor beta , estrogen receptor alpha , receptor , endocytosis , endocrinology , genetics , cancer , breast cancer
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.