Estrogen Receptor Alpha Splice Variants, Post-Translational Modifications, and Their Physiological Functions

Kenji Saito; Huxing Cui

doi:10.3390/cells12060895

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Estrogen Receptor Alpha Splice Variants, Post-Translational Modifications, and Their Physiological Functions

Journal article

Open access

Peer reviewed

Estrogen Receptor Alpha Splice Variants, Post-Translational Modifications, and Their Physiological Functions

Kenji Saito and Huxing Cui

Cells (Basel, Switzerland), Vol.12(6), 895

03/14/2023

DOI: 10.3390/cells12060895

PMCID: PMC10047206

PMID: 36980236

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Abstract

The importance of estrogenic signaling for a broad spectrum of biological processes, including reproduction, cancer development, energy metabolism, memory and learning, and so on, has been well documented. Among reported estrogen receptors, estrogen receptor alpha (ERα) has been known to be a major mediator of cellular estrogenic signaling. Accumulating evidence has shown that the regulations of ERα gene transcription, splicing, and expression across the tissues are highly complex. The ERα promoter region is composed of multiple leader exons and 5'-untranslated region (5'-UTR) exons. Differential splicing results in multiple ERα proteins with different molecular weights and functional domains. Furthermore, various post-translational modifications (PTMs) further impact ERα cellular localization, ligand affinity, and therefore functionality. These splicing isoforms and PTMs are differentially expressed in a tissue-specific manner, mediate certain aspects of ERα signaling, and may work even antagonistically against the full-length ERα. The fundamental understanding of the ERα splicing isoforms in normal physiology is limited and association studies of the splicing isoforms and the PTMs are scarce. This review aims to summarize the functional diversity of these ERα variants and the PTMs in normal physiological processes, particularly as studied in transgenic mouse models.

Alternative Splicing - genetics

Animals

Estrogen Receptor alpha - genetics

Estrogen Receptor alpha - metabolism

Exons

Mice

Protein Isoforms - genetics

Protein Isoforms - metabolism

Protein Processing, Post-Translational

Details

Title: Subtitle: Estrogen Receptor Alpha Splice Variants, Post-Translational Modifications, and Their Physiological Functions
Creators: Kenji Saito - University of Iowa
Huxing Cui - University of Iowa
Resource Type: Journal article
Publication Details: Cells (Basel, Switzerland), Vol.12(6), 895
DOI: 10.3390/cells12060895
PMID: 36980236
PMCID: PMC10047206
NLM abbreviation: Cells
ISSN: 2073-4409
eISSN: 2073-4409
Grant note: HL084207 / NIH HHS HL127673 / NIH HHS
Language: English
Date published: 03/14/2023
Academic Unit: Iowa Neuroscience Institute; Fraternal Order of Eagles Diabetes Research Center; Neuroscience and Pharmacology
Record Identifier: 9984381133002771

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