Site-specific ubiquitination: Deconstructing the degradation tag

Carroll, Emma C.; Marqusee, Susan

doi:10.1016/j.sbi.2022.102345

Cited by 14 publications

(8 citation statements)

References 79 publications

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“…This is not surprising since there are examples of other E3 ligases with low lysine specificity that target a large ubiquitination zone, where several lysines can be ubiquitinated [ 49 ]. The mutation of preferred ubiquitination sites does not prevent these E3s from ubiquitinating another site on the same substrate [ 50 ]. Lysines represent 5.7% of the total human proteome [ 51 ] but SNRPD2 has higher contents with 14.4% of this amino acid.…”

Section: Discussionmentioning

confidence: 99%

SNRPD2 Is a Novel Substrate for the Ubiquitin Ligase Activity of the Salmonella Type III Secretion Effector SlrP

Bullones-Bolaños

Araujo-Garrido

Fernández-García

et al. 2022

Biology

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SlrP is a protein with E3 ubiquitin ligase activity that is translocated by Salmonella enterica serovar Typhimurium into eukaryotic host cells through a type III secretion system. A yeast two-hybrid screen was performed to find new human partners for this protein. Among the interacting proteins identified by this screen was SNRPD2, a core component of the spliceosome. In vitro ubiquitination assays demonstrated that SNRPD2 is a substrate for the catalytic activity of SlrP, but not for other members of the NEL family of E3 ubiquitin ligases, SspH1 and SspH2. The lysine residues modified by this activity were identified by mass spectrometry. The identification of a new ubiquitination target for SlrP is a relevant contribution to the understanding of the role of this Salmonella effector.

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Section: Discussionmentioning

confidence: 99%

SNRPD2 Is a Novel Substrate for the Ubiquitin Ligase Activity of the Salmonella Type III Secretion Effector SlrP

Bullones-Bolaños

Araujo-Garrido

Fernández-García

et al. 2022

Biology

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“…Ubiquitination is a process enabling selective degradation of specific signaling proteins in cells under the action of specific enzymes; this process is crucial in protein metabolism, localization, function, degradation, and regulation. 22,23 Several studies have confirmed that ubiquitination is involved in the pathophysiology of SCI. Wu et al 24 reported that SCI upregulated the E3 ubiquitin ligase triad1, thus increasing the apoptosis of neurons through the p53-caspase3 pathway.…”

Section: Discussionmentioning

confidence: 98%

“…Ubiquitin is an 8.6 kDa protein widely present in eukaryotic cells. Ubiquitination is a process enabling selective degradation of specific signaling proteins in cells under the action of specific enzymes; this process is crucial in protein metabolism, localization, function, degradation, and regulation 22,23. Several studies have confirmed that ubiquitination is involved in the pathophysiology of SCI.…”

Section: Discussionmentioning

confidence: 99%

Hyperbaric Oxygen Treatment in Spinal Cord Injury Recovery: Profiling Long Noncoding RNAs

Liu

Liang

Sun

et al. 2022

Spine

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Study Design. A functional, transcriptome, and long noncoding RNAs (lncRNAs) expression analysis in the spinal cord of mice after hyperbaric oxygen (HBO) treatment. Objective. We aimed to explore the mechanism by which HBO treats spinal cord injury (SCI) at the level of lncRNAs. Summary of Background Data. Immense amounts of research have established that HBO treatment promotes the recovery of neurological function after SCI. The mechanism of action remains to be clarified. Methods. High-throughput RNA sequencing, Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes enrichment analysis were used to profile lncRNA expression and analyze biological function in the spinal cords of mice from sham-operated, SCI, and HBO-treated groups. The differential expression of lncRNA between the groups was assessed using real-time quantitative polymerase chain reaction. Results. Differential expression across 577 lncRNAs was identified among the three groups. GO analysis showed that free ubiquitin chain polymerization, ubiquitin homeostasis, DNA replication, synthesis of RNA primer, single-stranded telomeric DNA binding, and alpha-amylase activity were significantly enriched. Kyoto Encyclopedia of Genes and Genomes enrichment analysis displayed that vitamin B6 metabolism, one carbon pool by folate, DNA replication, lysine degradation, beta-alanine metabolism, fanconi anemia pathway, and Notch signal pathway were the main pathways with enrichment significance. LncRNAs NONMMUT 092674.1, NONMMUT042986.2, and NONMMUT018850.2 showed significantly different expression between the SCI and the other two groups (P<0.05, <0.01). Conclusions. This study is the first to determine the expression profiles of lncRNAs in the injured spinal cord after HBO treatment. We identified several important dysregulated lncRNAs in this setting. These results help us better understand the mechanism by which HBO treats SCI and provide new potential therapeutic targets for SCI.

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“…Ubiquitination can affect the biological functions of cells by regulating the stability and expression level of intracellular proteins, including cell proliferation, cell cycle, apoptosis, tumour development, metastasis, and invasion 39 . Changes in protein stability and abnormal expression are related to the development of diseases, and so the study of protein ubiquitination mechanisms can better explain the molecular mechanisms of diseases 40 , 41 . Ubiquitination was shown to modulate the stability of the NLRP3 inflammasome 42 , 43 .…”

Section: Discussionmentioning

confidence: 99%

TRIM59 suppresses the brain ischaemia/reperfusion injury and pyroptosis of microglial through mediating the ubiquitination of NLRP3

Zhang,

Li,

2024

Sci Rep

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Cerebral ischaemia/reperfusion (I/R) injury induces irreversible brain injury and causes functional impairment. Ubiquitination plays a crucial role in protein degradation, but its role in cerebral I/R injury remains unclear. Differentially expressed genes in stroke were identified by analysing the microarray dataset GSE119121. Cerebral I/R was simulated in vitro by treating human microglial HMC3 cells with oxygen–glucose deprivation/reperfusion (OGD/R). Cell viability was tested by Cell Counting Kit 8 (CCK-8) assays, and pyroptosis was examined by flow cytometry. Lactate dehydrogenase (LDH) and inflammatory cytokine secretion were measured by LDH cytotoxicity assays and enzyme-linked immunosorbent assay (ELISA), respectively. The cerebral I/R animal model was established by middle cerebral artery occlusion (MCAO) surgery in rats. Bioinformatic analysis indicated that tripartite motif-containing protein 59 (TRIM59) is downregulated in stroke, which was verified in cerebral I/R models. The upregulation of TRIM59 promoted viability and inhibited pyroptosis in OGD/R-treated microglia and alleviated cerebral I/R injury in vivo. TRIM59 attenuated NOD-like receptor family pyrin domain containing 3 (NLRP3) protein expression through ubiquitination, thus degrading NLRP3 and alleviating OGD/R-induced injury. TRIM59 relieves cerebral I/R injury in vivo and in vivo. Mechanistically, TRIM59 directly interacts with NLRP3 and inhibits NLRP3 through ubiquitination. Targeting the TRIM59/NLRP3 signalling axis may be an effective therapeutic strategy for cerebral I/R.

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Site-specific ubiquitination: Deconstructing the degradation tag

Cited by 14 publications

References 79 publications

SNRPD2 Is a Novel Substrate for the Ubiquitin Ligase Activity of the Salmonella Type III Secretion Effector SlrP

SNRPD2 Is a Novel Substrate for the Ubiquitin Ligase Activity of the Salmonella Type III Secretion Effector SlrP

Hyperbaric Oxygen Treatment in Spinal Cord Injury Recovery: Profiling Long Noncoding RNAs

TRIM59 suppresses the brain ischaemia/reperfusion injury and pyroptosis of microglial through mediating the ubiquitination of NLRP3

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