Functions and Molecular Mechanisms of Deltex Family Ubiquitin E3 Ligases in Development and Disease

Wang, Lidong; Sun, Xiaodan; He, Jingni; Liu, Zhen

doi:10.3389/fcell.2021.706997

Cited by 28 publications

(27 citation statements)

References 177 publications

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“…3 A). Deltex E3 has been principally studied in the context of tumorigenesis and tumour cell invasion [ 48 ], but very little is known about the roles played by Deltex E3 Ub ligases in the developing or adult brain in mammals. The marked enhancement of deltex gene expression supports the notion suggesting key roles in neuronal growth and differentiation in mammals.…”

Section: Resultsmentioning

confidence: 99%

Genome-wide analysis of genes encoding core components of the ubiquitin system during cerebral cortex development

Bouron

Fauvarque

2022

Mol Brain

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Ubiquitination involves three types of enzymes (E1, E2, and E3) that sequentially attach ubiquitin (Ub) to target proteins. This posttranslational modification controls key cellular processes, such as the degradation, endocytosis, subcellular localization and activity of proteins. Ubiquitination, which can be reversed by deubiquitinating enzymes (DUBs), plays important roles during brain development. Furthermore, deregulation of the Ub system is linked to the pathogenesis of various diseases, including neurodegenerative disorders. We used a publicly available RNA-seq database to perform an extensive genome-wide gene expression analysis of the core components of the ubiquitination machinery, covering Ub genes as well as E1, E2, E3 and DUB genes. The ubiquitination network was governed by only Uba1 and Ube2m, the predominant E1 and E2 genes, respectively; their expression was positively regulated during cortical formation. The principal genes encoding HECT (homologous to the E6-AP carboxyl terminus), RBR (RING-in-between-RING), and RING (really interesting new gene) E3 Ub ligases were also highly regulated. Pja1, Dtx3 (RING ligases) and Stub1 (U-box RING) were the most highly expressed E3 Ub ligase genes and displayed distinct developmental expression patterns. Moreover, more than 80 DUB genes were expressed during corticogenesis, with two prominent genes, Uch-l1 and Usp22, showing highly upregulated expression. Several components of the Ub system overexpressed in cancers were also highly expressed in the cerebral cortex under conditions not related to tumour formation or progression. Altogether, this work provides an in-depth overview of transcriptomic changes during embryonic formation of the cerebral cortex. The data also offer new insight into the characterization of the Ub system and may contribute to a better understanding of its involvement in the pathogenesis of neurodevelopmental disorders.

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Section: Resultsmentioning

confidence: 99%

Genome-wide analysis of genes encoding core components of the ubiquitin system during cerebral cortex development

Bouron

Fauvarque

2022

Mol Brain

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“…Strikingly, deltex-3-like ( DTX3L ) was up-regulated in the Notch signal pathway ( Figure 6 ); it is an E3 ubiquitin ligase and plays a key role in the cell-cycle-related processes and cell-cycle regulation [ 38 ]. DTX3L belongs to the DTX protein family and is closely associated with cell signal transduction, growth, differentiation, and apoptosis [ 39 ]. DTX3L forms a complex with PARP14 and together with PARP14 and PARP9 mediates proliferation [ 40 ].…”

Section: Discussionmentioning

confidence: 99%

Molecular Regulation of Yak Preadipocyte Differentiation and Proliferation by LncFAM200B and ceRNA Regulatory Network Analysis

Ran

Yang

Luo

et al. 2022

Cells

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The positive regulatory role of lncFAM200B in differentiation and lipid deposition in yak intramuscular preadipocytes has been demonstrated in our previous study. However, the regulatory mechanisms remain unclear. In this study, we aimed to produce complete mRNA and microRNA (miRNA) profiles after adenovirus-mediated lncFAM200B overexpression in yak preadipocytes using high-throughput sequencing. We constructed a competing endogenous RNA (ceRNA) network with lncFAM200B as the core and identified the functions of the selected target miRNA during cell proliferation and differentiation. We obtained 118 differentially expressed genes (DEGs) after lncFAM200B overexpression, 76 of which were up-regulated, including Notch signaling members NOTCH3, DTX3L, and HES4, and 42 DEGs were down-regulated, including genes related to the cell cycle (CCNA2, BUB1, CDC20, TOP2A, and KIF20A). Additionally, many ubiquitin-mediated proteolysis pathway members were also significantly up-regulated (BUA7, PML, TRIM21, and TRIM25). MiRNA sequencing showed that 13 miRNAs were significantly up-regulated, and 12 miRNAs were down-regulated. Among them, 29 targets of 10 differentially expressed miRNAs (DEMs) were differentially expressed, including miR-152-FBXO33, miR-6529a-TRIM21, miR-148c-NOTCH3, and the miR-6529b-HES4 axis. We further verified that overexpression and inhibition of miR-6529a can inhibit and promote, respectively, the proliferation and differentiation of preadipocytes. Taken together, our study not only revealed the regulatory network of lncFAM200B during yak preadipocytes differentiation but also laid a foundation for elucidating the cause for lower intramuscular fat content in yaks at the molecular level.

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“…Previous studies showed that Deltex acted as a positive regulator of Notch signalling. DTX1 regulated transcription independently of RBPJ and HES1 through co-activator EP300 [ 36 ]. Increased expression of Notch 1-2 and Dll1 was shown to be important in initiating osteogenic differentiation, while elevating Notch 3 expression occurred later in rat liver MSCs [ 28 ].…”

Section: Discussionmentioning

confidence: 99%

Gene Expression Profiles of Human Mesenchymal Stromal Cells Derived from Wharton’s Jelly and Amniotic Membrane before and after Osteo-Induction Using NanoString Platform

Hiew

Akhir

Teoh

2022

CIMB

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The use of perinatal mesenchymal stem cells (MSCs) in bone tissue regeneration and engineering to substitute bone marrow MSCs has drawn great interest due to their high yield, ease of procurement, multilineage differentiation potential and lack of ethical concerns. Although amniotic membrane (AM) and Wharton’s jelly (WJ)-derived MSCs have been widely shown to possess osteogenic differentiation potential, the intrinsic properties determining their osteogenic capacity remain unclear. Here, we compared gene expression profiles of AM- and WJ-MSCs at basal and osteogenic conditions by using the NanoString Stem Cell Panel containing regulatory genes associated with stemness, self-renewal, Wnt, Notch and Hedgehog signalling pathways. At basal condition, WJ-MSCs displayed higher expression in most genes regardless of their functional roles in self-renewal, adhesion, or differentiation signalling pathways. After osteo-induction, elevated expression of self-renewal genes ADAR and PAFAH1B1 was observed in AM-MSCs, while stemness genes MME and ALDH1A1 were upregulated in WJ-MSC. Both MSCs showed differences in genes associated with ligands, receptors and ubiquitin ligases of the Notch pathway. In addition, further evidence was demonstrated in some signalling molecules including CTBPs, protein kinases, phosphatases, RHOA, RAC1. Downstream targets HES1 and JUN especially showed higher expression in non-induced WJ-MSCs. Hedgehog genes initially expressed in both MSCs were downregulated in WJ-MSCs during osteogenesis. This study has provided insights into the intrinsic biological differences that may lead to their discrimination in therapeutic intervention.

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Functions and Molecular Mechanisms of Deltex Family Ubiquitin E3 Ligases in Development and Disease

Cited by 28 publications

References 177 publications

Genome-wide analysis of genes encoding core components of the ubiquitin system during cerebral cortex development

Genome-wide analysis of genes encoding core components of the ubiquitin system during cerebral cortex development

Molecular Regulation of Yak Preadipocyte Differentiation and Proliferation by LncFAM200B and ceRNA Regulatory Network Analysis

Gene Expression Profiles of Human Mesenchymal Stromal Cells Derived from Wharton’s Jelly and Amniotic Membrane before and after Osteo-Induction Using NanoString Platform

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