Emerging Roles of MHC Class I Region-Encoded E3 Ubiquitin Ligases in Innate Immunity

Jia, Xiuzhi; Zhao, Chenyang; Zhao, Wei

doi:10.3389/fimmu.2021.687102

Cited by 26 publications

(20 citation statements)

References 84 publications

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“…In addition, these TRIMs-B30.2 evolve significantly faster than other TRIMs based on the calculated ratio of the non-synonymous substitution rate ( Ka ) to the synonymous substitution rate ( Ks ) [ 4 ]. Recently, several studies have identified a cluster of TRIM-B30.2 genes flanking the human major histocompatibility complex (MHC) gene locus, a well-known immune gene [ 18 ]. Functional experiments have also demonstrated that TRIMs-B30.2 tend to be involved in host immune defense against viral infections in mammals.…”

Section: Introductionmentioning

confidence: 99%

Genome-Wide Identification and Expression Analysis of Potential Antiviral Tripartite Motif Proteins (TRIMs) in Grass Carp (Ctenopharyngodon idella)

Qin

Xiao

Ding

et al. 2021

Biology

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Tripartite motif proteins (TRIMs), especially B30.2 domain-containing TRIMs (TRIMs-B30.2), are increasingly well known for their antiviral immune functions in mammals, while antiviral TRIMs are far from being identified in teleosts. In the present study, we identified a total of 42 CiTRIMs from the genome of grass carp, Ctenopharyngodon idella, an important cultured teleost in China, based on hmmsearch and SMART analysis. Among these CiTRIMs, the gene loci of 37 CiTRIMs were located on different chromosomes and shared gene collinearities with homologous counterparts from human and zebrafish genomes. They possessed intact conserved RBCC or RB domain assemblies at their N-termini and eight different domains, including the B30.2 domain, at their C-termini. A total of 19 TRIMs-B30.2 were identified, and most of them were clustered into a large branch of CiTRIMs in the dendrogram. Tissue expression analysis showed that 42 CiTRIMs were universally expressed in various grass carp tissues. A total of 11 significantly differentially expressed CiTRIMs were found in two sets of grass carp transcriptomes during grass carp reovirus (GCRV) infection. Three of them, including Cibtr40, CiTRIM103 and CiTRIM109, which all belonged to TRIMs-B30.2, were associated with the type I interferon response during GCRV infection by weighted network co-expression and gene expression trend analyses, suggesting their involvement in antiviral immunity. These findings may offer useful information for understanding the structure, evolution, and function of TRIMs in teleosts and provide potential antiviral immune molecule markers for grass carp.

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Section: Introductionmentioning

confidence: 99%

Genome-Wide Identification and Expression Analysis of Potential Antiviral Tripartite Motif Proteins (TRIMs) in Grass Carp (Ctenopharyngodon idella)

Qin

Xiao

Ding

et al. 2021

Biology

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“…While no obvious functional associations were identified in gene set enrichment analysis of the significant DMPs and DMRs from our regression analysis, the within-pair analysis identified enrichment in immune-related terms. The top DMR identified in this study is located in the gene body of TRIM39-RPP21 , a read-through transcript enjoining the N-terminus RING finger and B-box domains of TRIM39 and RPP21 and located within the major histocompatibility complex class I region of chromosome 6 22 , 23 . The nine associated probes in this region are hypomethylated in cases compared to controls.…”

Section: Discussionmentioning

confidence: 90%

DNA methylation at birth in monozygotic twins discordant for pediatric acute lymphoblastic leukemia

Nickels

Myint

et al. 2022

Nat Commun

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Aberrant DNA methylation constitutes a key feature of pediatric acute lymphoblastic leukemia at diagnosis, however its role as a predisposing or early contributor to leukemia development remains unknown. Here, we evaluate DNA methylation at birth in 41 leukemia-discordant monozygotic twin pairs using the Illumina EPIC array on archived neonatal blood spots to identify epigenetic variation associated with development of pediatric acute lymphoblastic leukemia, independent of genetic influence. Through conditional logistic regression we identify 240 significant probes and 10 regions associated with the discordant onset of leukemia. We identify a significant negative coefficient bias, indicating DNA hypomethylation in cases, across the array and enhanced in open sea, shelf/shore, and gene body regions compared to promoter and CpG island regions. Here, we show an association between global DNA hypomethylation and future development of pediatric acute lymphoblastic leukemia across disease-discordant genetically identical twins, implying DNA hypomethylation may contribute more generally to leukemia risk.

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“…Membrane-anchored E3 ligases of the Modulator of Immune Recognition (MIR) family of E3 ligases affect antigen presentation by regulating lysosomal degradation of MHC class I antigens [ 76 ]. Multiple E3 ubiquitin ligase genes of the TRIM family are located in the MHC Class I region of chromosome 6 [ 77 ]. This includes TRIM27 , a gene included in the heatmap of differentially expressed E3 ligases in EPN ( Figure 5 ).…”

Section: Discussionmentioning

confidence: 99%

“…The network analysis of Figure 6 illustrates the interaction of other E3 ligases on TRIM27 expression. The expression is related to inflammatory disesases and viral infections [ 77 ]. While some TRIM proteins have been associated with cancer [ 78 ], we could find no previous reports relating TRIM27 to EPN tumorigenesis.…”

Section: Discussionmentioning

confidence: 99%

Ubiquitin Proteasome Gene Signatures in Ependymoma Molecular Subtypes

Vriend

Thanasupawat

Sinha

et al. 2022

IJMS

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The ubiquitin proteasome system (UPS) is critically important for cellular homeostasis and affects virtually all key functions in normal and neoplastic cells. Currently, a comprehensive review of the role of the UPS in ependymoma (EPN) brain tumors is lacking but may provide valuable new information on cellular networks specific to different EPN subtypes and reveal future therapeutic targets. We have reviewed publicly available EPN gene transcription datasets encoding components of the UPS pathway. Reactome analysis of these data revealed genes and pathways that were able to distinguish different EPN subtypes with high significance. We identified differential transcription of several genes encoding ubiquitin E2 conjugases associated with EPN subtypes. The expression of the E2 conjugase genes UBE2C, UBE2S, and UBE2I was elevated in the ST_EPN_RELA subtype. The UBE2C and UBE2S enzymes are associated with the ubiquitin ligase anaphase promoting complex (APC/c), which regulates the degradation of substrates associated with cell cycle progression, whereas UBE2I is a Sumo-conjugating enzyme. Additionally, elevated in ST_EPN_RELA were genes for the E3 ligase and histone deacetylase HDAC4 and the F-box cullin ring ligase adaptor FBX031. Cluster analysis demonstrated several genes encoding E3 ligases and their substrate adaptors as EPN subtype specific genetic markers. The most significant Reactome Pathways associated with differentially expressed genes for E3 ligases and their adaptors included antigen presentation, neddylation, sumoylation, and the APC/c complex. Our analysis provides several UPS associated factors that may be attractive markers and future therapeutic targets for the subtype-specific treatment of EPN patients.

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Emerging Roles of MHC Class I Region-Encoded E3 Ubiquitin Ligases in Innate Immunity

Cited by 26 publications

References 84 publications

Genome-Wide Identification and Expression Analysis of Potential Antiviral Tripartite Motif Proteins (TRIMs) in Grass Carp (Ctenopharyngodon idella)

Genome-Wide Identification and Expression Analysis of Potential Antiviral Tripartite Motif Proteins (TRIMs) in Grass Carp (Ctenopharyngodon idella)

DNA methylation at birth in monozygotic twins discordant for pediatric acute lymphoblastic leukemia

Ubiquitin Proteasome Gene Signatures in Ependymoma Molecular Subtypes

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