Dynamic transcriptional events mediated by estrogen receptor alpha

Ayaz, Gamze; Yaşar, Pelin; Olgun, Çağla Ece; Karakaya, Burcu; Kars, Gizem; Razizadeh, Negin; Yavuz, Kerim; Turan, Gizem; Muyan, Mesut

doi:10.2741/4716

Cited by 11 publications

(6 citation statements)

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“…These receptors are located in the cytoplasm. Following ligand binding, they undergo conformational changes, dimerize and translocate to the nucleus, where the receptor-ligand complex binds to specific DNA sequences (called estrogen-responsive elements -EREs) and result in transcription of new proteins [21][22][23][24] .…”

Section: Treatment Of Pmopmentioning

confidence: 99%

Selective estrogen receptor modulators in post-menopausal osteoporosis

Falsetti

Palmini

Aurilia

et al. 2022

International Journal of Bone Fragility

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Osteoporosis (OP) is a chronic disease that occurs when the balance between the processes of bone formation and resorption is lost. OP is characterized by a decrease in bone quality and an increased risk of fractures. In post-menopausal women, as a result of decreased estrogen levels, there is bone loss. Hormone replacement therapy was initially used for the management of OP in post-menopausal women but was soon abandoned due to the occurrence of significant side effects. This shifted research toward the development of a class of drugs called selective estrogen receptor modulators (SERMs). These drugs always act through estrogen receptors (ERs), but as agonists or antagonists depending on the tissue under consideration. In particular, SERMs at the level of bone tissue behave as agonists of ERs but, as they do not result in the occurrence of estrogen side effects, they are widely used in the therapy of post-menopausal OP. This review provides a brief summary of the characteristics of SERMs employed in the treatment of post-menopausal OP.

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Section: Treatment Of Pmopmentioning

confidence: 99%

Selective estrogen receptor modulators in post-menopausal osteoporosis

Falsetti

Palmini

Aurilia

et al. 2022

International Journal of Bone Fragility

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“…1A). Moreover, change in the occupancy of ERα binding to its specific DNA binding element, oestrogen responsive element (ERE), was modelled using β‐oestradiol‐bound ERα as the ligand, where Y ERE is the fractional saturation of ERE, K d2 is the dissociation constant of active ERα from ERE [39], and C ERα is the concentration of ERα in the cell.

Y_{normalERE} = {()(, \frac{K_{d 2}}{Y_{normalE normalR normalα} \cdot C_{normalE normalR normalα}} + 1)}^{‐ 1}

…”

Section: Regulation Of Oestrogen Responsivenessmentioning

confidence: 99%

ERK1/2‐RSK regulation of oestrogen homeostasis

Wright

Lannigan

2022

The FEBS Journal

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The molecular mechanisms regulating oestrogen homeostasis have been primarily studied in the mammary gland, which is the focus of this review. In the non‐pregnant adult, the mammary gland undergoes repeated cycles of proliferation and apoptosis in response to the fluctuating levels of oestrogen that occur during the reproductive stage. Oestrogen actions are mediated through the steroid hormone receptors, oestrogen receptor α and β and through a G‐protein coupled receptor. In the mammary gland, ERα is of particular importance and thus will be highlighted. Mechanisms regulating oestrogen‐induced responses through ERα are necessary to maintain homeostasis given that the signalling pathways that are activated in response to ERα‐mediated transcription can also induce transformation. ERK1/2 and its downstream effector, p90 ribosomal S6 kinase (RSK), control homeostasis in the mammary gland by limiting oestrogen‐mediated ERα responsiveness. ERK1/2 drives degradation coupled ERα‐mediated transcription, whereas RSK2 acts as a negative regulator of ERK1/2 activity to limit oestrogen responsiveness. Moreover, RSK2 acts as a positive regulator of translation. Thus, RSK2 provides both positive and negative signals to maintain oestrogen responsiveness. In addition to transmitting signals through tyrosine kinase receptors, ERK1/2‐RSK engages with hedgehog signalling to maintain oestrogen levels and with the HIPPO pathway to regulate ERα‐mediated transcription. Additionally, ERK1/2‐RSK controls the progenitor populations within the mammary gland to maintain the ERα‐positive population. RSK2 is involved in increased breast cancer risk in individuals taking oral contraceptives and in parity‐induced protection against breast cancer. RSK2 and ERα may also co‐operate in diseases in tissues outside of the mammary gland.

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“…17β-Estradiol (E2), the most potent estrogen hormone in the circulation, is involved in a wide variety of vital physiological functions ranging from the development and maintenance of reproductive organs to the regulation of cardiovascular, musculoskeletal, immune, and central nervous system homeostasis [1][2][3] . Effects of E2 on cells are primarily mediated by estrogen receptors (ER) α and β, which are the products of distinct genes and act as transcription factors [1][2][3] . Upon binding to E2, the activated ER modulates the expression of E2 target genes, whose protein products are involved in the regulation of cellular proliferation, differentiation, and death [1][2][3] .…”

Section: Introductionmentioning

confidence: 99%

“…Effects of E2 on cells are primarily mediated by estrogen receptors (ER) α and β, which are the products of distinct genes and act as transcription factors [1][2][3] . Upon binding to E2, the activated ER modulates the expression of E2 target genes, whose protein products are involved in the regulation of cellular proliferation, differentiation, and death [1][2][3] . Despite the contribution of both inherited and environmental factors, perturbations in E2 signaling are considered to be the major factor for the initiation and development of estrogen-target tissue malignancies, including breast cancer [1][2][3] .…”

Section: Introductionmentioning

confidence: 99%

“…Upon binding to E2, the activated ER modulates the expression of E2 target genes, whose protein products are involved in the regulation of cellular proliferation, differentiation, and death [1][2][3] . Despite the contribution of both inherited and environmental factors, perturbations in E2 signaling are considered to be the major factor for the initiation and development of estrogen-target tissue malignancies, including breast cancer [1][2][3] . Due to the central role of the E2-ERα signaling in the physiology and pathophysiology of estrogen target tissues, identifying estrogen-responsive genes and functional characterization of their protein products involved in the manifestation of cellular phenotype could provide new prognostic tools and/or therapeutic targets.…”

Section: Introductionmentioning

confidence: 99%

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Dynamic proximity interaction profiling suggests that YPEL2 is involved in cellular stress surveillance

Turan,

Olgun,

Ayten

et al. 2023

Preprint

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YPEL2 is a member of the evolutionarily conserved YPEL family involved in cellular proliferation, mobility, differentiation as well as senescence and death. However, the mechanism by which YPEL2, or YPEL proteins, mediates its effects is yet unknown. Proteins perform their functions in a network of proteins whose identities, amounts, and compositions change spatiotemporally in a lineage-specific manner in response to internal and external stimuli. We here explored interaction partners of YPEL2 by using dynamic TurboID-coupled mass spectrometry analyses to infer a function for the protein. Our results using inducible transgene expressions in COS7 cells indicate that proximity interaction partners of YPEL2 are largely involved in RNA and mRNA metabolic processes, ribonucleoprotein complex biogenesis, regulation of gene silencing by miRNA, and cellular responses to stress. We showed that YPEL2 interacts with RNA binding protein ELAVL1 and selective autophagy receptor SQSTM1. We also found that YPEL2 participates in events associated with the formation/disassembly of stress granules in response to sodium arsenite an oxidative stress inducer. Establishing a point of departure in the delineation of structural/functional features of YPEL2, our results suggest that YPEL2 may be involved in stress surveillance mechanisms.

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Dynamic transcriptional events mediated by estrogen receptor alpha

Cited by 11 publications

References 0 publications

Selective estrogen receptor modulators in post-menopausal osteoporosis

Selective estrogen receptor modulators in post-menopausal osteoporosis

ERK1/2‐RSK regulation of oestrogen homeostasis

Dynamic proximity interaction profiling suggests that YPEL2 is involved in cellular stress surveillance

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