Liganded ERα Stimulates the E3 Ubiquitin Ligase Activity of UBE3C to Facilitate Cell Proliferation
| Autor: | Yasushi Saeki, Hiroyuki Nishikawa, Fumiaki Ohtake, Keiji Takana, Maiko Okada, Wenwen Wu, Tomohiko Ohta |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
Ubiquitin-Protein Ligases
Mitosis Estrogen receptor Breast Neoplasms Spindle Apparatus Biology Endocrinology Cell Line Tumor Humans Cyclin B1 Molecular Biology Estrogen receptor beta Original Research Cell Proliferation Anaphase Cell growth Estrogen Antagonists Estrogen Receptor alpha Ubiquitination General Medicine Ubiquitin ligase Tamoxifen MCF-7 Cells biology.protein Cancer research Female Estrogen receptor alpha hormones hormone substitutes and hormone antagonists |
| Zdroj: | Molecular Endocrinology. 29:1646-1657 |
| ISSN: | 1944-9917 0888-8809 |
| Popis: | Estrogen receptor (ER)α is a well-characterized ligand-dependent transcription factor. However, the global picture of its nongenomic functions remains to be illustrated. Here, we demonstrate a novel function of ERα during mitosis that facilitates estrogen-dependent cell proliferation. An E3 ubiquitin ligase, UBE3C, was identified in an ERα complex from estrogen-treated MCF-7 breast cancer cells arrested at mitosis. UBE3C interacts with ERα during mitosis in an estrogen-dependent manner. In vitro, estrogen dramatically stimulates the E3 activity of UBE3C in the presence of ERα. This effect was inhibited by the estrogen antagonist tamoxifen. Importantly, estrogen enhances the ubiquitination of cyclin B1 (CCNB1) and destabilizes CCNB1 during mitosis in a manner dependent on endogenous UBE3C. ERα, UBE3C, and CCNB1 colocalize in prophase nuclei and at metaphase spindles before CCNB1 is degraded in anaphase. Depletion of UBE3C attenuates estrogen-dependent cell proliferation without affecting the transactivation function of ERα. Collectively, these results demonstrate a novel ligand-dependent action of ERα that stimulates the activity of an E3 ligase. The mitotic role of estrogen may contribute to its effects on proliferation in addition to its roles in target gene expression. |
| Databáze: | OpenAIRE |
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