Polyubiquitination inhibition of estrogen receptor alpha and its implications in breast cancer

World Journal of Clinical Oncology
Angeles C Tecalco-Cruz, Josué O Ramírez-Jarquín

Abstract

Estrogen receptor alpha (ERα) is detected in more than 70% of the cases of breast cancer. Nuclear activity of ERα, a transcriptional regulator, is linked to the development of mammary tumors, whereas the extranuclear activity of ERα is related to endocrine therapy resistance. ERα polyubiquitination is induced by the estradiol hormone, and also by selective estrogen receptor degraders, resulting in ERα degradation via the ubiquitin proteasome system. Moreover, polyubiquitination is related to the ERα transcription cycle, and some E3-ubiquitin ligases also function as coactivators for ERα. Several studies have demonstrated that ERα polyubiquitination is inhibited by multiple mechanisms that include posttranslational modifications, interactions with coregulators, and formation of specific protein complexes with ERα. These events are responsible for an increase in ERα protein levels and deregulation of its signaling in breast cancers. Thus, ERα polyubiquitination inhibition may be a key factor in the progression of breast cancer and resistance to endocrine therapy.

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Citations

Oct 17, 2018·Current Drug Targets·Angeles C Tecalco-CruzEduardo Cruz-Ramos
Jul 9, 2020·Frontiers in Pharmacology·Jing-Wen BaiGuo-Jun Zhang
Sep 17, 2020·Cells·Sarah A JeffreysTherese M Becker
Aug 31, 2021·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Sadia AfrinMostafa A Borahay

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Methods Mentioned

BETA
ubiquitination
biopsy
acetylation
transgenic

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