MOAP-1, UBR5 and cisplatin resistance in ovarian cancer

Eblen, Scott T.; Bradley, Amber

doi:10.21037/tcr.2017.02.01

Cited by 6 publications

(4 citation statements)

References 21 publications

(39 reference statements)

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“…The PI3K/Akt signaling pathway is associated with cell survival and proliferation in various types of cancer ( 14 , 30 ), indicating that the role of UBR5 in gastric cancer proliferation may be mediated via the PI3K/Akt signaling pathway. In addition, UBR5, acting as an ubiquitin ligase, can directly degrade modulator of apoptosis protein 1 (MOAP-1) by ubiquitylation, thereby inhibiting MOAP-1 stability, and MOAP-1 exerts an effect by enhancing the expression of the proapoptotic protein-Bax ( 9 , 19 ). Therefore, whether inhibition of UBR5 can decrease gastric cancer cell proliferation via MOAP-1 requires further investigation.…”

Section: Discussionmentioning

confidence: 99%

UBR5 oncogene as an indicator of poor prognosis in gastric cancer

et al. 2020

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The human ubiquitin protein ligase E3 component N-recognin 5 (UBR5) gene, which is localized to chromosome 8q22, encodes an ~10 kb mRNA and a >300 kDa protein, which can be detected in a number of cell types. UBR5 is implicated in several types of cancer, including ovarian cancer, gallbladder cancer and lymphoma; however, its role in gastric cancer is not completely understood. In the present study, the expression levels of UBR5 in human gastric cancer tissues and cell lines were examined via immunohistochemistry, reverse transcription-quantitative PCR analysis and western blotting. Furthermore, the association between UBR5 expression and clinicopathological characteristics, as well as the prognosis of patients with gastric cancer, were examined. In addition, the role of UBR5 in gastric cancer cell proliferation, invasion and migration was investigated by conducting MTS, Transwell and wound healing assays, respectively. The results indicated that the mRNA and protein expression levels of UBR5 were significantly increased in gastric cancer tissues compared with para-carcinoma tissues. High UBR5 expression levels were significantly associated with larger tumor size, advanced TNM stage and lymph node metastasis. In addition, high UBR5 expression indicated a poor prognosis in patients with gastric cancer. Furthermore, in vitro experiments demonstrated that UBR5 knockdown was associated with reduced HGC-27 gastric cancer cell proliferation, invasion and migration compared with the small interfering RNA control group. Therefore, the results indicated that UBR5 may serve a key role in gastric cancer, indicating that UBR5 may also serve as an important prognostic biomarker.

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Section: Discussionmentioning

confidence: 99%

UBR5 oncogene as an indicator of poor prognosis in gastric cancer

et al. 2020

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“…UBR5 is reported to enhance cell survival and cisplatin resistance by regulation of expression of the pro-survival protein myeloid cell leukaemia sequence 1 (Mcl-1) and is an undesirable prognostic factor for patients with serous epithelial ovarian cancer [112]. UBR5 influences ovarian cancer cell cisplatin resistance by mediating MOAP-1 ubiquitylation and degradation through cooperation with Dyrk2 kinase [113].…”

Section: Role Of E3 Ligases In Diseasementioning

confidence: 99%

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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“…They further showed that UBR5 might have modulated ovarian cancer cell survival through regulating expression of the prosurvival protein myeloid cell leukemia sequence 1 (Mcl-1) [ 55 ] . As a novel ubiquitin ligase for the proapoptotic protein modulator of apoptosis protein 1 (MOAP-1, also known as MAP-1), UBR5 influences ovarian cancer cell cisplatin resistance by mediating MOAP-1 ubiquitination and degradation through cooperation with Dyrk2 kinase [ 56 , 57 ] . UBR5 upregulation in recurrent and platinum-resistant ovarian cancers indicates that targeting UBR5 may be an effective strategy for chemoresistant ovarian cancer treatment [ 57 ] .…”

Section: E3 Ubiquitin Ligases In Ovarian Cancer Chemoresistancementioning

confidence: 99%

The emerging roles of E3 ubiquitin ligases in ovarian cancer chemoresistance

Meng¹,

Qiu²,

Zhang³

et al. 2021

CDR

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Epithelial cancer of the ovary exhibits the highest mortality rate of all gynecological malignancies in women today, since the disease is often diagnosed in advanced stages. While the treatment of cancer with specific chemical agents or drugs is the favored treatment regimen, chemotherapy resistance greatly impedes successful ovarian cancer chemotherapy. Thus, chemoresistance becomes one of the most critical clinical issues confronted when treating patients with ovarian cancer. Convincing evidence hints that dysregulation of E3 ubiquitin ligases is a key factor in the development and maintenance of ovarian cancer chemoresistance. This review outlines recent advancement in our understanding of the emerging roles of E3 ubiquitin ligases in ovarian cancer chemoresistance. We also highlight currently available inhibitors targeting E3 ligase activities and discuss their potential for clinical applications in treating chemoresistant ovarian cancer patients.

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MOAP-1, UBR5 and cisplatin resistance in ovarian cancer

Cited by 6 publications

References 21 publications

UBR5 oncogene as an indicator of poor prognosis in gastric cancer

UBR5 oncogene as an indicator of poor prognosis in gastric cancer

Functional Significance of the E3 Ubiquitin Ligases in Disease and Therapeutics

The emerging roles of E3 ubiquitin ligases in ovarian cancer chemoresistance

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