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Curr Drug Targets. 2019;20(6):690-704. doi: 10.2174/1389450119666181015114041.

Estrogen Receptor Alpha and its Ubiquitination in Breast Cancer Cells.

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Instituto de Investigaciones Biomedicas. Universidad Nacional Autonoma de Mexico. Mexico City, 04510, Mexico.
Instituto de Fisiologia Celular. Universidad Nacional Autonoma de Mexico. Mexico City, 04510, Mexico.


More than 70% of all breast cancer cases are estrogen receptor alpha-positive (ERα). ERα is a member of the nuclear receptor family, and its activity is implicated in the gene transcription linked to the proliferation of breast cancer cells, as well as in extranuclear signaling pathways related to the development of resistance to endocrine therapy. Protein-protein interactions and posttranslational modifications of ERα underlie critical mechanisms that modulate its activity. In this review, the relationship between ERα and ubiquitin protein (Ub), was investigated in the context of breast cancer cells. Interestingly, Ub can bind covalently or non-covalently to ERα resulting in either a proteolytic or non-proteolytic fate for this receptor. Thereby, Ub-dependent molecular pathways that modulate ERα signaling may play a central role in breast cancer progression, and consequently, present critical targets for treatment of this disease.


Estrogen receptor alpha; breast cancer; endocrine therapy; monoubiquitination; non-covalent ubiquitin binding; polyubiquitination.

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