The emerging roles of E3 ubiquitin ligases in ovarian cancer chemoresistance

Meng, Yan; Qiu, Lei; Zhang, Su; Han, Junhong

doi:10.20517/cdr.2020.115

Cited by 8 publications

(11 citation statements)

References 150 publications

(185 reference statements)

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“…These include the Nedd4 family, which are characterised by the presence of tryptophan-tryptophan (WW) motifs, the HERC (HECT and RCC1-like domain) family, which contain one or more regulators of chromosome condensation 1 (RCC1)-like domains (RLDs), and the SI (ngle)-HECT/"other" HECT E3s lacking either WW or RLDs domains but contain various other domains. These subfamilies have been extensively reviewed [58]. HECT domain E3s play several roles.…”

Section: Hect E3 Ligasesmentioning

confidence: 99%

“…Aberrations of ubiquitin signalling are often associated with pathogenesis of several diseases and genetic disorders [58,[70][71][72][73]. Errors in ubiquitin signalling processes result in defective autophagy and mitophagy, DNA repair mechanisms, NF-kB signalling, etc.…”

Section: Role Of E3 Ligases In Diseasementioning

confidence: 99%

“…Ubiquitin E3 ligases, most notably RING finger and RING finger-related E3s are fundamental to the specificity of the ubiquitin proteasome system. Many RING finger E3s are implicated in either the suppression or the progression of cancer and cancer chemoresistance [58,75,77,78]. Due to limited space only some key E3-linked diseases have been explained below.…”

Section: Role Of E3 Ligases In Diseasementioning

confidence: 99%

“…Multiple studies have implicated several E3 ubiquitin ligases in ovarian cancer chemoresistance which hamper improvement of ovarian cancer patient outcome through degradation of various chemoresistance-related substrates in ovarian cancer. Among several studies, [107] demonstrated that NEDD4-2 protein (an E3 ligase that regulates endocytosis and lysosomal degradation of ENaC and other channels) expression is reduced in invasive ovarian epithelial cancer tissues compared with non-cancer ovarian tissue suggesting an important role of NEDD4-2 in the regulation of chemoresistant ovarian cancer [58]. Indeed Nedd4-1 and Nedd4-2 E3 ligases have been demonstrated to mediate numerous pathophysiological Ligase processes [108].…”

Section: Role Of E3 Ligases In Diseasementioning

confidence: 99%

“…Being enzymes and mostly natural tumour suppressors, many E3 ligases function within these criteria and are therefore attractive targets for therapeutic intervention of cancers. Several studies have explored and validated the therapeutic potential of E3 ligases [58,71,72]. In this section, the rationale for selected E3 ligases with pharmacological potential have been reviewed.…”

Section: Potential Therapeutic Benefits Of E3 Ligasesmentioning

confidence: 99%

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Functional Significance of the E3 Ubiquitin Ligases in Disease and Therapeutics

Dongdem¹,

Opare-Asamoah²

2022

Hydrolases

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E3 ubiquitin ligases of which there are >600 putative in humans, constitute a family of highly heterogeneous proteins and protein complexes that are the ultimate enzymes responsible for the recruitment of an ubiquitin loaded E2 ubiquitin-conjugating enzyme, recognise the appropriate protein substrate and directly or indirectly transfer the ubiquitin load onto the substrate. The aftermath of an E3 ligase activity is usually the formation of an isopeptide bond between the free carboxylate group of ubiquitin’s C-terminal Gly76 and an ε-amino group of the substrate’s Lys, even though non-canonical ubiquitylation on non-amine groups of target proteins have been observed. E3 ligases are grouped into four distinct families: HECT, RING-finger/U-box, RBR and PHD-finger. E3 ubiquitin ligases play critical roles in subcellular signalling cascades in eukaryotes. Dysfunctional E3 ubiquitin ligases therefore tend to inflict dramatic effects on human health and may result in the development of various diseases including Parkinson’s, Amyotrophic Lateral Sclerosis, Alzheimer’s, cancer, etc. Being regulators of numerous cellular processes, some E3 ubiquitin ligases have become potential targets for therapy. This chapter will present a comprehensive review of up-to-date findings in E3 ligases, their role in the pathology of disease and therapeutic potential for future drug development.

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Section: Hect E3 Ligasesmentioning

confidence: 99%

Section: Role Of E3 Ligases In Diseasementioning

confidence: 99%

Section: Role Of E3 Ligases In Diseasementioning

confidence: 99%

Section: Role Of E3 Ligases In Diseasementioning

confidence: 99%

Section: Potential Therapeutic Benefits Of E3 Ligasesmentioning

confidence: 99%

See 3 more Smart Citations

Functional Significance of the E3 Ubiquitin Ligases in Disease and Therapeutics

Dongdem¹,

Opare-Asamoah²

2022

Hydrolases

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Targeting CRL4 suppresses chemoresistant ovarian cancer growth by inducing mitophagy

Meng

Qiu

Zeng

et al. 2022

Sig Transduct Target Ther

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Chemoresistance has long been the bottleneck of ovarian cancer (OC) prognosis. It has been shown that mitochondria play a crucial role in cell response to chemotherapy and that dysregulated mitochondrial dynamics is intricately linked with diseases like OC, but the underlying mechanisms remain equivocal. Here, we demonstrate a new mechanism where CRL4CUL4A/DDB1 manipulates OC cell chemoresistance by regulating mitochondrial dynamics and mitophagy. CRL4CUL4A/DDB1 depletion enhanced mitochondrial fission by upregulating AMPKαThr172 and MFFSer172/Ser146 phosphorylation, which in turn recruited DRP1 to mitochondria. CRL4CUL4A/DDB1 loss stimulated mitophagy through the Parkin-PINK1 pathway to degrade the dysfunctional and fragmented mitochondria. Importantly, CRL4CUL4A/DDB1 loss inhibited OC cell proliferation, whereas inhibiting autophagy partially reversed this disruption. Our findings provide novel insight into the multifaceted function of the CRL4 E3 ubiquitin ligase complex in regulating mitochondrial fission, mitophagy, and OC chemoresistance. Disruption of CRL4CUL4A/DDB1 and mitophagy may be a promising therapeutic strategy to overcome chemoresistance in OC.

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A novel machine learning model based on ubiquitin-related gene pairs and clinical features to predict prognosis and treatment effect in colon adenocarcinoma

et al. 2023

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Background Ubiquitin and ubiquitin-like (UB/UBL) conjugations are essential post-translational modifications that contribute to cancer onset and advancement. In colon adenocarcinoma (COAD), nonetheless, the biological role, as well as the clinical value of ubiquitin-related genes (URGs), is unclear. The current study sought to design and verify a ubiquitin-related gene pairs (URGPs)-related prognostic signature for predicting COAD prognoses. Methods Using univariate, least absolute shrinkage and selection operator (LASSO), and multivariate Cox regression, URGP's predictive signature was discovered. Signatures differentiated high-risk and low-risk patients. ROC and Kaplan–Meier assessed URGPs' signature. Gene set enrichment analysis (GSEA) examined biological nomogram enrichment. Chemotherapy and tumor immune microenvironment were also studied. Results The predictive signature used six URGPs. High-risk patients had a worse prognosis than low-risk patients, according to Kaplan–Meier. After adjusting for other clinical characteristics, the URGPs signature could reliably predict COAD patients. In the low-risk group, we found higher amounts of invading CD4 memory-activated T cells, follicular helper T cells, macrophages, and resting dendritic cells. Moreover, low-risk group had higher immune checkpoint-related gene expression and chemosensitivity. Conclusion Our research developed a nomogram and a URGPs prognostic signature to predict COAD prognosis, which may aid in patient risk stratification and offer an effective evaluation method of individualized treatment in clinical settings.

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The emerging roles of E3 ubiquitin ligases in ovarian cancer chemoresistance

Cited by 8 publications

References 150 publications

Functional Significance of the E3 Ubiquitin Ligases in Disease and Therapeutics

Functional Significance of the E3 Ubiquitin Ligases in Disease and Therapeutics

Targeting CRL4 suppresses chemoresistant ovarian cancer growth by inducing mitophagy

A novel machine learning model based on ubiquitin-related gene pairs and clinical features to predict prognosis and treatment effect in colon adenocarcinoma

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