The ubiquitin conjugating enzyme UBE2L3 regulates TNFα-induced linear ubiquitination

Fu, Bishi; Li, Shitao; Wang, Lingyan; Berman, Michael A.; Dorf, Martin E.

doi:10.1038/cr.2013.133

Cited by 41 publications

(39 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…UBE2L3 encodes an E2 ubiquitin‐conjugating enzyme. Through its action on ubiquitination in NF‐κB signaling, UBE2L3 promotes NF‐κB activation, thus mediates its link with numerous autoimmune diseases . Moreover, UBE2L3 modulates pro‐IL‐1β processing and mature IL‐1β secretion, the deregulation of which pronouncedly intensifies neuronal damage in both AD and IS .…”

Section: Discussionmentioning

confidence: 99%

“…Through its action on ubiquitination in NF-κB signaling, UBE2L3 promotes NF-κB activation, thus mediates its link with numerous autoimmune diseases. [51][52][53] Moreover, UBE2L3 modulates pro-IL-1β processing and mature IL-1β secretion, 54 the deregulation of which pronouncedly intensifies neuronal damage in both AD and IS. 55,56 In addition, UBE2L3 directly interacts with the parkin protein, a ubiquitin-protein ligase that is protective against not only neurodegenerative diseases, [57][58][59] but also cerebral ischemia-reperfusion injury.…”

Section: Ube2l3 Ydjc and Slc2a11 Genes At 22q11mentioning

confidence: 99%

See 1 more Smart Citation

Shared genes between Alzheimer’s disease and ischemic stroke

Wei

Cui

et al. 2019

CNS Neurosci Ther

View full text Add to dashboard Cite

Summary Aims Although converging evidence from experimental and epidemiological studies indicates Alzheimer's disease (AD) and ischemic stroke (IS) are related, the genetic basis underlying their links is less well characterized. Traditional SNP‐based genome‐wide association studies (GWAS) have failed to uncover shared susceptibility variants of AD and IS. Therefore, this study was designed to investigate whether pleiotropic genes existed between AD and IS to account for their phenotypic association, although this was not reported in previous studies. Methods Taking advantage of large‐scale GWAS summary statistics of AD (17,008 AD cases and 37,154 controls) and IS (10,307 IS cases and 19,326 controls), we performed gene‐based analysis implemented in VEGAS2 and Fisher's meta‐analysis of the set of overlapped genes of nominal significance in both diseases. Subsequently, gene expression analysis in AD‐ or IS‐associated expression datasets was conducted to explore the transcriptional alterations of pleiotropic genes identified. Results 16 AD‐IS pleiotropic genes surpassed the cutoff for Bonferroni‐corrected significance. Notably, MS4A4A and TREM2 , two established AD‐susceptibility genes showed remarkable alterations in the spleens and brains afflicted by IS, respectively. Among the prioritized genes identified by virtue of literature‐based knowledge, most are immune‐relevant genes ( EPHA1 , MS4A4A , UBE2L3 and TREM2 ), implicating crucial roles of the immune system in the pathogenesis of AD and IS. Conclusions The observation that AD and IS had shared disease‐associated genes offered mechanistic insights into their common pathogenesis, predominantly involving the immune system. More importantly, our findings have important implications for future research directions, which are encouraged to verify the involvement of these candidates in AD and IS and interpret the exact molecular mechanisms of action.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Ube2l3 Ydjc and Slc2a11 Genes At 22q11mentioning

confidence: 99%

Shared genes between Alzheimer’s disease and ischemic stroke

Wei

Cui

et al. 2019

CNS Neurosci Ther

View full text Add to dashboard Cite

show abstract

“…In this study, we explored its role by RNA‐seq and some molecular experiments and found that UBE2L3 may facilitate cellular proliferation and migration by degrading CDKN2B and CLDN1, but more solid experiments are needed to clarify its mechanism. Secondly, UBE2L3 facilitates conjugation of linear ubiquitin chains in cells and then activates cytokine‐mediated NF‐B signalling, which may facilitate the carcinogenesis in HCC. In a recent study, UBE2L3 was involved in the regulation of the linear ubiquitin chain assembly complex .…”

Section: Discussionmentioning

confidence: 99%

UBE2L3, a susceptibility gene that plays oncogenic role in hepatitis B‐related hepatocellular carcinoma

Liu

Song

et al. 2018

Journal of Viral Hepatitis

View full text Add to dashboard Cite

Previously, we identified UBE2L3 as a susceptibility gene for chronic hepatitis B virus (HBV) infection through genome-wide association study. Here, we analysed the association between genetic variants of UBE2L3 and the susceptibility to HBV-related hepatocellular carcinoma (HCC) and further explored its role in HCC. This case-control study included 1344 subjects who cleared HBV, 1560 HBV carriers and 1057 HBV-related HCC patients. Two single nucleotide polymorphisms (SNPs) were genotyped, including rs2266959 and rs4821116. Logistic regression analysis was performed to compute the odds ratio (OR) and 95% confidence interval (CI). We further analysed the expression of UBE2L3 and its association with pathological features based on The Cancer Genome Atlas (TCGA) data and our tissue microarray. Proliferation and migration assays were performed in hepatoma cell lines with or without UBE2L3 knockdown. Further RNA-seq analysis was performed to explore the underlying oncogenic mechanism. The variant genotypes of rs4821116 in UBE2L3 were associated with decreased risk for HCC and chronic HBV infection. Moreover, based on both TCGA and our tissue microarray data, higher levels of UBE2L3 expression were correlated with higher tumour grade, advanced tumour stage and poor survival. In vitro analysis revealed that UBE2L3 may promote hepatocyte proliferation and migration. RNA-seq analysis showed that UBE2L3 was inversely correlated with CDKN2B, a negative regulator of cell cycle, and CLDN1, loss of which may promote cancer metastasis. In conclusion, UBE2L3 may also be a susceptibility gene in HBV-related HCC, and it may promote HCC proliferation and migration by negatively regulating CDKN2B and CLDN1.

show abstract

“…Interestingly, UBE2L3 has also been shown to be part of the cytokine induced NF‐kB signaling pathway, where it plays a critical role in recruiting components to the tumor necrosis factor receptor 1 (TNFR1) signaling complex . In particular, the absence of UBE2L3 blocks the recruitment of NF‐kB essential modulator (NEMO) to the tumor necrosis factor receptor 1 (TNFR1) signaling complex resulting in the inhibition of the subsequent induction of proinflammatory gene expression . Markedly, NF‐kB activation can lead to the activation of the inflammasome which has been implicated in CHIKV pathogenesis, and downregulation of UBE2L3 may serve to dampen this antiviral mechanism.…”

Section: Discussionmentioning

confidence: 99%