Estrogen Receptor Alpha Splice Variants, Post-Translational Modifications, and Their Physiological Functions
Abstract
:1. Estrogen Receptor Alpha (ERα)
2. Complex Organization of ERα 5′-UTR
3. ERα Isoform Variation and Functions
3.1. Differential Splicing
3.1.1. ERα46
3.1.2. ERα36
3.1.3. ERαV/ERαΔ3-6
3.1.4. ERα-LBD
3.1.5. N-Terminally Truncated ERα Products (NTERPs)/Truncated Estrogen Receptor Products (TERPs)
3.1.6. ERαΔ3, ERαΔ4, ERαΔ3/4
3.1.7. ERα-Neo KO Mouse
3.2. Post-Translational Modifications
3.2.1. S118 Phosphorylation
Site in Human ERα | Site in Mouse ERα | Modification | Physiological Functions | References |
---|---|---|---|---|
S118 | S122 | Phosphorylation | Dimerization of ERα/transcriptional regulation | [59,60] |
Sexually dimorphic effects on fat accumulation; amino acid substitution to non-phosphorylatable form leads to more fat accumulation in female mice and lower fat mass in male mice | [65,66] | |||
S212 | S216 | Phosphorylation | Transcriptional regulation via ERE | [67] |
Amino acid substitution to non-phosphorylatable form increases inflammatory signatures and impairs motor coordination | [68] | |||
R260 | R264 | Methylation | ERα cytoplasmic distribution | [69] |
Amino acid substitution to non-methylatable form impairs membrane-initiated actions of E2 in the endothelial cells | [70] | |||
C447 | C451 | Palmitoylation | ERα plasma membrane localization | [71,72] |
Amino acid substitution to non-palmitoylable form leads to female mouse infertility and impairs the homeostatic regulation of trabecular bone in the axial skeleton | [73,74,75] | |||
Y537 | Y541 | Phosphorylation | E2-ERα binding/interaction with kinases | [76,77] |
Amino acid substitution to non-phosphorylatable form leads to female mouse infertility | [78] |
3.2.2. S212 Phosphorylation
3.2.3. R260 Methylation
3.2.4. C447 Palmitoylation
3.2.5. Y537 Phosphorylation
3.3. New Unidentified Variant
4. Perspectives
Author Contributions
Funding
Institutional Review Board Statement
Data Availability Statement
Conflicts of Interest
References
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Isoform | MW (kDa) | Species | Tissues Detected | Physiological Functions/Properties | References |
---|---|---|---|---|---|
ERα46 | 46 | Human | ovary, liver, skeletal muscle, lung, kidney, adrenal gland |
| [9,10,11,12] |
Mouse | heart, uterus, testis |
| [13] | ||
Rat | pituitary |
| [12] | ||
ERα36 | 36 | Human | breast cancer endometrial cells, mammary gland, uterus |
| [14,15] |
| [16] | ||||
| [17] | ||||
| [13,18] | ||||
Mouse | kidney, ovary, oocytes |
| [13] | ||
ERαV/ΔE3-6 | 37 | Human | brain, MCF-7 cells |
| [19,20] |
ERα-LBD | 37.3 | Human | breast cancer |
| [21] |
NTERPs | 37.3 | Mouse | pituitary, brain, ovary, testis, kidney |
| [22] |
TERPs | 20–24 | Rat | pituitary |
| [22,23,24,25,26] |
| [24] | ||||
ERαΔE3/ΔE4/ΔE3/4 | 61.8/53/45 | Rat | pituitary |
| [27,28,29,30] |
ERαΔE4 | 52 | Human | MCF-7 cells, pituitary, ovarian carcinoma |
| [31,32,33] |
52 | Mouse | N-38 immortalized hypothalamic neurons |
| [30,34,35] | |
ERα66* | 67–70 | Mouse | pituitary, brain, ovary, testis, liver |
| [36] |
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Saito, K.; Cui, H. Estrogen Receptor Alpha Splice Variants, Post-Translational Modifications, and Their Physiological Functions. Cells 2023, 12, 895. https://doi.org/10.3390/cells12060895
Saito K, Cui H. Estrogen Receptor Alpha Splice Variants, Post-Translational Modifications, and Their Physiological Functions. Cells. 2023; 12(6):895. https://doi.org/10.3390/cells12060895
Chicago/Turabian StyleSaito, Kenji, and Huxing Cui. 2023. "Estrogen Receptor Alpha Splice Variants, Post-Translational Modifications, and Their Physiological Functions" Cells 12, no. 6: 895. https://doi.org/10.3390/cells12060895