The structure and regulation of Cullin 2 based E3 ubiquitin ligases and their biological functions

Cai, Weijia; Yang, Haifeng

doi:10.1186/s13008-016-0020-7

Cited by 61 publications

(52 citation statements)

References 149 publications

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“…Therefore, Twist1 promoted Cul2 mRNA transcription but not translation. Cul2 has been predicted to be a tumor suppressor protein because of its association with the von Hippel-Lindau gene and ubiquitinated HIFa degradation (18,19). However, it has also been reported that Cul2 is required for normal vasculogenesis and involved in cell-cycle regulation (20) and that it promotes gastric cancer progression (35,36).…”

Section: Discussionmentioning

confidence: 99%

“…Cullin2 (Cul2) is a core component of multiple ECS (ElonginB/C-CUL2/5-SOCS-box protein) E3 ubiquitin-protein ligase complexes, which mediate the ubiquitination of target proteins. Cul2 was predicted to be a tumor-suppressor protein that degrades ubiquitinated HIFa (18,19). However, it has also been reported that Cul2 is required for normal vasculogenesis and is involved in cell-cycle regulation (20).…”

Section: Introductionmentioning

confidence: 99%

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Twist1 Regulates Vimentin through Cul2 Circular RNA to Promote EMT in Hepatocellular Carcinoma

et al. 2018

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Twist is a critical epithelial-mesenchymal transition (EMT)-inducing transcription factor that increases expression of vimentin. How Twist1 regulates this expression remains unclear. Here, we report that Twist1 regulates Cullin2 (Cul2) circular RNA to increase expression of vimentin in EMT. Twist1 bound the Cul2 promoter to activate its transcription and to selectively promote expression of Cul2 circular RNA (circ-10720), but not mRNA. circ-10720 positively correlated with Twist1, tumor malignance, and poor prognosis in hepatocellular carcinoma (HCC). Twist1 promoted vimentin expression by increasing levels of circ-10720, which can absorb miRNAs that target vimentin. circ-10720 knockdown counteracted the tumor-promoting activity of Twist1 and in patient-derived xenograft and diethylnitrosamine-induced TetOn-Twist1 transgenic mouse HCC models. These data unveil a mechanism by which Twist1 regulates vimentin during EMT. They also provide potential therapeutic targets for HCC treatment and provide new insight for circular RNA (circRNA)-based diagnostic and therapeutic strategies. A circRNA-based mechanism drives Twist1-mediated regulation of vimentin during EMT and provides potential therapeutic targets for treatment of HCC. http://cancerres.aacrjournals.org/content/canres/78/15/4150/F1.large.jpg .

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Twist1 Regulates Vimentin through Cul2 Circular RNA to Promote EMT in Hepatocellular Carcinoma

et al. 2018

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“…Twist as an important EMT-TF that directly or indirectly governs the transcription of EMT-associated genes, thereby decreasing epithelial markers, such as E-cad, and increasing mesenchymal cell markers, including vimentin [54]. Cullin2 (Cul2) is a core component of multiple ElonginB/C-CUL2/5-SOCS-box protein (ECS) E3 ubiquitin-protein ligase complexes that mediate the ubiquitination of target proteins [55,56]. A study has validated that Twist1 promotes Cul2 transcription by binding to the Cul2 promoter and increases the pre-mRNA levels of Cul2.…”

Section: Regulation Of Twist On Vimentin By Circrnasmentioning

confidence: 99%

Functional roles of circular RNAs during epithelial-to-mesenchymal transition

Shang¹,

Li²,

Quan³

et al. 2019

Mol Cancer

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Cancer has become a major health issue worldwide, contributing to a high mortality rate. Tumor metastasis is attributed to the death of most patients. Epithelial-to-mesenchymal transition (EMT) plays a vital role in inducing metastasis. During EMT, epithelial cells lose their characteristics, such as cell-to-cell adhesion and cell polarity, and cells gain motility, migratory potential, and invasive properties to become mesenchymal stem cells. Circular RNAs (circRNAs) are closely associated with tumor metastasis and patient prognosis, as revealed by increasing lines of evidence. CircRNA is a type of single-stranded RNA that forms a covalently closed continuous loop. CircRNAs are insensitive to ribonucleases and are widespread in body fluids. This work is the first review on EMT-related circRNAs. In this review, we briefly discuss the characteristics and functions of circRNAs. The correlation of circRNAs with EMT has been reported, and we discuss the ways circRNAs can regulate EMT progression through EMT transcription factors, EMT-related signaling pathways, and other mechanisms. This work summarizes current studies on EMTrelated circRNAs in various cancers and provides a theoretical basis for the use of EMT-related circRNAs in targeted management and therapy.

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“…First isolated as a partner of specific protein kinase C isoforms, for which it was named receptor for activated C-kinase (4–8), RACK1 has also been shown to interact with a considerable number of other signal transduction proteins, including the cAMP-specific phosphodiesterase PDE4D5 (9–17), the tyrosine kinase oncoproteins SRC (18–21), FLT1 (22), and FAK (23), protein serine phosphatase PP2A (24–26), the MAPKs JNK1 and ERK1/2 (27), VARP (28), phospholipase C (29), the NMDA receptor (30–33), cytokine and growth factor receptors (34–38), G sβγ (39–42), selected 14.3.3 isoforms (43) and likely other signaling proteins (44–47). RACK1 also interacts with members of complexes that play important roles in protein degradation, such as the Cullin-2 based E3 ubiquitin ligases (48;48;49), as well as certain enzymes of unclear cellular function, such as inositol-requiring enzyme 1 (IRE1; refs, (50)). RACK1 also may interact with elements of the cytoskeleton, including β-integrins (51–56) and β-actin (21;21;57).…”

Section: Introductionmentioning

confidence: 99%

The RNA-binding protein SERBP1 interacts selectively with the signaling protein RACK1

Bolger

2017

Cellular Signalling

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The RACK1 protein interacts with numerous proteins involved in signal transduction, the cytoskeleton, and mRNA splicing and translation. We used the 2-hybrid system to identify additional proteins interacting with RACK1 and isolated the RNA-binding protein SERBP1. SERPB1 shares amino acid sequence homology with HABP4 (also known as Ki-1/57), a component of the RNA spicing machinery that has been shown previously to interact with RACK1. Several different isoforms of SERBP1, generated by alternative mRNA splicing, interacted with RACK1 with indistinguishable interaction strength, as determined by a 2-hybrid beta-galactosidase assay. Analysis of deletion constructs of SERBP1 showed that the C-terminal third of the SERBP1 protein, which contains one of its two substrate sites for protein arginine N-methyltransferase 1 (PRMT1), is necessary and sufficient for it to interact with RACK1. Analysis of single amino acid substitutions in RACK1, identified in a reverse 2-hybrid screen, showed very substantial overlap with those implicated in the interaction of RACK1 with the cAMP-selective phosphodiesterase PDE4D5. These data are consistent with SERBP1 interacting selectively with RACK1, mediated by an extensive interaction surface on both proteins.

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The structure and regulation of Cullin 2 based E3 ubiquitin ligases and their biological functions

Cited by 61 publications

References 149 publications

Twist1 Regulates Vimentin through Cul2 Circular RNA to Promote EMT in Hepatocellular Carcinoma

Twist1 Regulates Vimentin through Cul2 Circular RNA to Promote EMT in Hepatocellular Carcinoma

Functional roles of circular RNAs during epithelial-to-mesenchymal transition

The RNA-binding protein SERBP1 interacts selectively with the signaling protein RACK1

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