Ubiquitin ligase RNF5 serves an important role in the development of human glioma

Gao, Yong; Xuan, Chengmin; Jin, Man-Wen; An, Q.; Zhuo, Baobiao; Chen, Xincheng; Wang, Lei; Wang, Yuan; Sun, Qingzeng; Shi, Yingchun

doi:10.3892/ol.2019.10801

Cited by 12 publications

(9 citation statements)

References 34 publications

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“…The degradation of intracellular proteins is mainly accomplished by the ubiquitin-proteasome system, and the ubiquitin-proteasome have strong selectivity for protein degradation [ 23 ]. Studies have shown that the ubiquitination pathway is closely related to the occurrence and development of tumors [ 1 , 2 , 8 , 9 , 19 ]. Here we identified six differentially expressed URGs that were related to survival in glioma patients.…”

Section: Discussionmentioning

confidence: 99%

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Identification of ubiquitination-related genes in human glioma as indicators of patient prognosis

et al. 2021

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Ubiquitination is a dynamic and reversible process of a specific modification of target proteins catalyzed by a series of ubiquitination enzymes. Because of the extensive range of substrates, ubiquitination plays a crucial role in the localization, metabolism, regulation, and degradation of proteins. Although the treatment of glioma has been improved, the survival rate of patients is still not satisfactory. Therefore, we explore the role of ubiquitin proteasome in glioma. Survival-related ubiquitination related genes (URGs) were obtained through analysis of the Genotype-Tissue Expression (GTEx) and the Cancer Genome Atlas (TCGA). Cox analysis was performed to construct risk model. The accuracy of risk model is verified by survival, Receiver operating characteristic (ROC) and Cox analysis. We obtained 36 differentially expressed URGs and found that 25 URGs were related to patient prognosis. We used the 25 URGs to construct a model containing 8 URGs to predict glioma patient risk by Cox analysis. ROC showed that the accuracy rate of this model is 85.3%. Cox analysis found that this model can be used as an independent prognostic factor. We also found that this model is related to molecular typing markers. Patients in the high-risk group were enriched in multiple tumor-related signaling pathways. In addition, we predicted TFs that may regulate the risk model URGs and found that the risk model is related to B cells, CD4 T cells, and neutrophils.

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Section: Discussionmentioning

confidence: 99%

“…The ubiquitination pathway is a highly conserved post-translational modification process regulated by a series of enzymes [ 1 , 2 ]. It plays a leading role in the degradation of most proteins in eukaryotic cells.…”

Section: Introductionmentioning

confidence: 99%

Identification of ubiquitination-related genes in human glioma as indicators of patient prognosis

et al. 2021

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“…Furthermore, RNF5 was able to degrade phosphoglycerate dehydrogenase (PHGDH), the first enzyme of the serine synthesis pathway, which is significantly upregulated in many cancers [ 14 ]. Finally, high expression of RNF5 in patients with glioma was associated with an improved prognosis compared to patients with low expression [ 15 ]. Given the controversial pathophysiological role of RNF5 in cancer, we extended the study of its functional expression to neuroblastoma (NB) and melanoma, which represent two neuroectodermal tumors of infancy and adulthood, respectively, with the same embryonal origin and poor prognosis.…”

Section: Introductionmentioning

confidence: 99%

Targeting of Ubiquitin E3 Ligase RNF5 as a Novel Therapeutic Strategy in Neuroectodermal Tumors

Principi

Sondo

Bianchi

et al. 2022

Cancers

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RNF5, an endoplasmic reticulum (ER) E3 ubiquitin ligase, participates to the ER-associated protein degradation guaranteeing the protein homeostasis. Depending on tumor model tested, RNF5 exerts pro- or anti-tumor activity. The aim of this study was to elucidate the controversial role of RNF5 in neuroblastoma and melanoma, two neuroectodermal tumors of infancy and adulthood, respectively. RNF5 gene levels are evaluated in publicly available datasets reporting the gene expression profile of melanoma and neuroblastoma primary tumors at diagnosis. The therapeutic effect of Analog-1, an RNF5 pharmacological activator, was investigated on in vitro and in vivo neuroblastoma and melanoma models. In both neuroblastoma and melanoma patients the high expression of RNF5 correlated with a better prognostic outcome. Treatment of neuroblastoma and melanoma cell lines with Analog-1 reduced cell viability by impairing the glutamine availability and energy metabolism through inhibition of F1Fo ATP-synthase activity. This latter event led to a marked increase in oxidative stress, which, in turn, caused cell death. Similarly, neuroblastoma- and melanoma-bearing mice treated with Analog-1 showed a significant delay of tumor growth in comparison to those treated with vehicle only. These findings validate RNF5 as an innovative drug target and support the development of Analog-1 in early phase clinical trials for neuroblastoma and melanoma patients.

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“…RNF5 is a Ub E3 ligase, anchored to the endoplasmic reticulum (ER) membrane and crucial components of the ER-associated degradation (ERAD) process [ 71 ]. Based on the Cancer Cell Line Encyclopedia (CCLE) and TCGA database, mRNA expression level of RNF5 is abundant in AML compared to other cancer types, and there is a positive correlation between high RNF5 expression and poor survival [ 72 ].…”

Section: Ubiquitination In Amlmentioning

confidence: 99%

Acute Myeloid Leukemia-Related Proteins Modified by Ubiquitin and Ubiquitin-like Proteins

Park

Baek

2022

IJMS

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Acute myeloid leukemia (AML), the most common form of an acute leukemia, is a malignant disorder of stem cell precursors of the myeloid lineage. Ubiquitination is one of the post-translational modifications (PTMs), and the ubiquitin-like proteins (Ubls; SUMO, NEDD8, and ISG15) play a critical role in various cellular processes, including autophagy, cell-cycle control, DNA repair, signal transduction, and transcription. Also, the importance of Ubls in AML is increasing, with the growing research defining the effect of Ubls in AML. Numerous studies have actively reported that AML-related mutated proteins are linked to Ub and Ubls. The current review discusses the roles of proteins associated with protein ubiquitination, modifications by Ubls in AML, and substrates that can be applied for therapeutic targets in AML.

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Ubiquitin ligase RNF5 serves an important role in the development of human glioma

Cited by 12 publications

References 34 publications

Identification of ubiquitination-related genes in human glioma as indicators of patient prognosis

Identification of ubiquitination-related genes in human glioma as indicators of patient prognosis

Targeting of Ubiquitin E3 Ligase RNF5 as a Novel Therapeutic Strategy in Neuroectodermal Tumors

Acute Myeloid Leukemia-Related Proteins Modified by Ubiquitin and Ubiquitin-like Proteins

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