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

Tecalco-Cruz, Ángeles C.; Ramírez-Jarquín, Josué O.

doi:10.5306/wjco.v9.i4.60

Cited by 15 publications

(13 citation statements)

References 112 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Since ER alpha signaling is recognized as the driver pathway in the majority of breast cancer patients, the understanding of dysregulation of ER alpha signaling is of utmost importance. Recent studies have shown that several kinds of posttranslational modifications involved in ER alpha stability could contribute to amplified ER alpha signaling and tamoxifen resistance 14,15 . Several E3 ligases are shown to promote ER alpha signaling through stabilizing ER alpha protein, such as RNF31, SHAPRIN, and RNF8 7,16,17 .…”

Section: Introductionmentioning

confidence: 99%

Regulation of estrogen signaling and breast cancer proliferation by an ubiquitin ligase TRIM56

Xue

Zhang

et al. 2019

Oncogenesis

View full text Add to dashboard Cite

Breast cancer ranks no. 1 in women cancer worldwide, while 60–70% are estrogen receptor alpha positive. The estrogen selective modulators, such as tamoxifen, become the effective drugs for controlling ER alpha breast cancer progression. However, tamoxifen resistance will develop during long-time treatment and cancer progression. Thus, further understanding of ER alpha signaling becomes necessary for the improvement of breast cancer therapy. Here, we identify TRIM56 as a novel regulatory factor in ER alpha signaling. TRIM56 expression is positively correlated with ER alpha and PR in breast cancer samples and is related to poor prognosis in endocrine therapy patients. TRIM56 depletion significantly decreases ER alpha signaling activity and ER-alpha-positive breast cancer proliferation in vitro and in vivo. TRIM56 associates with AF1 domain of ER alpha via its WD40 domain in the cytoplasm. TRIM56 prolongs ER alpha protein stability, possibly through targeting ER alpha K63-linked ubiquitination. In conclusion, our study reveals an interesting posttranslational mechanism between TRIM56 and ER alpha in breast cancer progression. Targeting TRIM56 could be a promising approach for ER-alpha-positive breast cancer.

show abstract

Section: Introductionmentioning

confidence: 99%

Regulation of estrogen signaling and breast cancer proliferation by an ubiquitin ligase TRIM56

Xue

Zhang

et al. 2019

Oncogenesis

View full text Add to dashboard Cite

show abstract

“…Whilst ER is produced through transcription and protein synthesis, changes to ER degradation kinetics is the major factor determining ER levels. In BCa, there is an imbalance between the rate of transcription, synthesis and degradation of the ER leading to increased ER stability and thus activity [45]. The half-life of the ER differs significantly depending on estrogen exposure.…”

Section: Estrogen Receptor Turnovermentioning

confidence: 99%

“…Monoubiquitylation increases the stability and transcriptional activity of the receptor, whilst further addition of ubiquitin, polyubiquitylation, targets the protein for degradation by the UPS [53]. Some proteins have an inhibitory effect on ubiquitylation which leads to increased stability of the ER associated with ET resistance, broadly classified as coactivators, E3 ligases, kinases and scaffold proteins [45].…”

Section: Ubiquitylationmentioning

confidence: 99%

See 1 more Smart Citation

Endocrine Resistance in Breast Cancer: The Role of Estrogen Receptor Stability

Jeffreys

Powter

Balakrishnar

et al. 2020

Cells

View full text Add to dashboard Cite

Therapy of hormone receptor positive breast cancer (BCa) generally targets estrogen receptor (ER) function and signaling by reducing estrogen production or by blocking its interaction with the ER. Despite good long-term responses, resistance to treatment remains a significant issue, with approximately 40% of BCa patients developing resistance to ET. Mutations in the gene encoding ERα, ESR1, have been identified in BCa patients and are implicated as drivers of resistance and disease recurrence. Understanding the molecular consequences of these mutations on ER protein levels and its activity, which is tightly regulated, is vital. ER activity is in part controlled via its short protein half-life and therefore changes to its stability, either through mutations or alterations in pathways involved in protein stability, may play a role in therapy resistance. Understanding these connections and how ESR1 alterations could affect protein stability may identify novel biomarkers of resistance. This review explores the current reported data regarding posttranslational modifications (PTMs) of the ER and the potential impact of known resistance associated ESR1 mutations on ER regulation by affecting these PTMs in the context of ET resistance.

show abstract

“…Molecular aspects of ERα-mediated transcriptions include allosteric mechanisms related to the intracellular traffics of the receptor and cofactor recruitments [8,9,[45][46][47][48][49][50][51]. These events analyzed in details in Sections 5-7 are briefly described here under to stress their importance to satisfy homeostasis or evolution.…”

Section: Factors Implicated In the Irreversible Character Of Erα-medimentioning

confidence: 99%

Pathological Maintenance and Evolution of Breast Cancer: The Convergence of Irreversible Biological Actions of ER Alpha

Leclercq

2020

Endocrines

View full text Add to dashboard Cite

Estrogen receptor alpha (ERα) is a modulator of breast cancer maintenance and evolution. Hence, analysis of underlying mechanisms by which ERα operates is of importance for the improvement of the hormonal therapy of the disease. This review focuses on the irreversible character of the mechanism of action of ERα, which also concerns other members of the steroid hormones receptors family. ERα moves in permanence between targets localized especially at the chromatin level to accomplish gene transcriptions imposed by the estrogenic ligands and specific antagonists. Receptor association as at the plasma membrane, where it interacts with other recruitment sites, extends its regulatory potency to growth factors and related peptides through activation of signal transductions pathways. If the latter procedure is suitable for the transcriptions in which the receptor operates as a coregulator of another transcription factor, it is of marginal influence with regard to the direct estrogenic regulation procedure, especially in the context of the present review. Irreversibility of the successive steps of the underlying transcription cycle guarantees maintenance of homeostasis and evolution according to vital necessities. To justify this statement, reported data are essentially described in a holistic view rather than in the context of exhaustive analysis of a molecular event contributing to a specific function as well as in a complementary perspective to elaborate new therapeutic approaches with antagonistic potencies against those tumors promoting ERα properties.

show abstract

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

Cited by 15 publications

References 112 publications

Regulation of estrogen signaling and breast cancer proliferation by an ubiquitin ligase TRIM56

Regulation of estrogen signaling and breast cancer proliferation by an ubiquitin ligase TRIM56

Endocrine Resistance in Breast Cancer: The Role of Estrogen Receptor Stability

Pathological Maintenance and Evolution of Breast Cancer: The Convergence of Irreversible Biological Actions of ER Alpha

Contact Info

Product

Resources

About