Estrogen receptor α L429 and A430 regulate 17β-estradiol-induced cell proliferation via CREB1.

Cellular Signalling
Valeria PesiriFilippo Acconcia

Abstract

17β-Estradiol (E2)-dependent cell proliferation requires both estrogen receptor α (ERα)-based integrated control of gene transcription and kinase pathways activation. Such coordination of intracellular E2:ERα-dependent signaling mechanisms is finely tuned by receptor association with specific partner proteins. Recently, we identified the leucine (L) 429 and alanine (A) 430 within the ERα ligand binding domain as important residues for receptor non-covalent interaction to ubiquitinated species [i.e., ERα ubiquitin-binding surface (ERα UBS)] and for E2-induced ERα activation. To date, if these two ERα amino acids are involved in the control of E2-dependent pathways required for cell proliferation is unknown. Here, by using stably expressing ERα mutated in L429 and A430 (i.e., L429A,A430G-LAAG) cell lines, we show that L429 and A430 are critical for E2-induced cell proliferation, PI3K/AKT pathway activation, and ERα-mediated transcriptional changes. Moreover, we demonstrate that these two receptor structural determinants direct the E2-induced PI3K/AKT/CREB1 pathway activation and CREB1-mediated transcriptional activity that in turn control the hormone-induced cell proliferation. As a whole, our data demonstrate for the first time ...Continue Reading

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Citations

May 18, 2016·The International Journal of Biochemistry & Cell Biology·Karsen SetoSubhajit Dasgupta
Dec 9, 2017·Journal of Cellular Physiology·Marco FiocchettiMaria Marino
May 20, 2016·IUBMB Life·Valeria PesiriFilippo Acconcia
Sep 17, 2020·International Journal of Molecular Sciences·Marco Segatto, Valentina Pallottini
Aug 29, 2021·Proceedings of the National Academy of Sciences of the United States of America·Vera A van der WeijdenSusanne E Ulbrich

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