更新于：2024-09-19

UBE2V1

更新于：2024-09-19

基本信息

别名

CROC-1、CROC1、TRAF6-regulated IKK activator 1 beta Uev1A

+ [7]

简介

Has no ubiquitin ligase activity on its own. The UBE2V1-UBE2N heterodimer catalyzes the synthesis of non-canonical poly-ubiquitin chains that are linked through Lys-63. This type of poly-ubiquitination activates IKK and does not seem to involve protein degradation by the proteasome. Plays a role in the activation of NF-kappa-B mediated by IL1B, TNF, TRAF6 and TRAF2. Mediates transcriptional activation of target genes. Plays a role in the control of progress through the cell cycle and differentiation. Plays a role in the error-free DNA repair pathway and contributes to the survival of cells after DNA damage. Promotes TRIM5 capsid-specific restriction activity and the UBE2V1-UBE2N heterodimer acts in concert with TRIM5 to generate 'Lys-63'-linked polyubiquitin chains which activate the MAP3K7/TAK1 complex which in turn results in the induction and expression of NF-kappa-B and MAPK-responsive inflammatory genes. Together with RNF135 and UBE2N, catalyzes the viral RNA-dependent 'Lys-63'-linked polyubiquitination of RIGI to activate the downstream signaling pathway that leads to interferon beta production (PubMed:31006531). UBE2V1-UBE2N together with TRAF3IP2 E3 ubiquitin ligase mediate 'Lys-63'-linked polyubiquitination of TRAF6, a component of IL17A-mediated signaling pathway.

关联

100 项与 UBE2V1 相关的临床结果

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100 项与 UBE2V1 相关的转化医学

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0 项与 UBE2V1 相关的专利（医药）

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141

项与 UBE2V1 相关的文献（医药）

2024-11-01·Meat Science

Sequential window acquisition of all theoretical mass spectra (SWATH-MS) as an emerging proteomics approach for the discovery of dark-cutting beef biomarkers

Article

作者: González-Blanco, Laura ; Bravo, Susana B ; Oliván, Mamen ; Sierra, Verónica ; Diñeiro, Yolanda ; Gagaoua, Mohammed

Recent advances in "omics" technologies have enabled the identification of new beef quality biomarkers and have also allowed for the early detection of quality defects such as dark-cutting beef, also known as DFD (dark, firm, and dry) beef. However, most of the studies conducted were carried out on a small number of animals and mostly applied gel-based proteomics. The present study proposes for the first time a Sequential Window Acquisition of All Theoretical Mass Spectra (SWATH-MS) proteomics approach to characterize and comprehensively quantify the post-mortem muscle proteome of DFD (pH₂₄ ≥ 6.2) and CONTROL (5.4 ≤ pH₂₄ ≤ 5.6) beef samples within the largest database of DFD/CONTROL beef samples to date (26 pairs of the Longissimus thoracis muscle samples of young bulls from Asturiana de los Valles breed, n = 52). The pairwise comparison yielded 35 proteins that significantly differed in their abundances between the DFD and CONTROL samples. Chemometrics methods using both PLS-DA and OPLS-DA revealed 31 and 36 proteins with VIP > 2.0, respectively. The combination of different statistical methods these being Volcano plot, PLS-DA and OPLS-DA allowed us to propose 16 proteins as good candidate biomarkers of DFD beef. These proteins are associated with interconnected biochemical pathways related to energy metabolism (DHRS7B and CYB5R3), binding and signaling (RABGGTA, MIA3, BPIFA2B, CAP2, APOBEC2, UBE2V1, KIR2DL1), muscle contraction, structure and associated proteins (DMD, PFN2), proteolysis, hydrolases, and activity regulation (AGT, C4A, GLB1, CAND2), and calcium homeostasis (ANXA6). These results evidenced the potential of SWATH-MS and chemometrics to accurately identify novel biomarkers for meat quality defects, providing a deeper understanding of the molecular mechanisms underlying dark-cutting beef condition.

2024-09-01·Cytokine

A systematic approach introduced some immune system targets in rectal cancer by considering cell-free DNA methylation in response to radiochemotherapy

Article

作者: Esmati, Ebrahim ; Khalighfard, Solmaz ; Poorkhani, Amirhoushang ; Hajizadeh, Mohammad Reza ; Alizadeh, Ali Mohammad ; Khori, Vahid ; Bagheri-Hosseinabadi, Zahra ; Mahmoodi, Mehdi ; Lashgari, Marzih ; Sadani, Somayeh ; Eshkevari, Seyed Mohammad Sadat ; Amiriani, Taghi

BACKGROUNDThis study aims to investigate cell-free DNA (cfDNA) methylation of genes involved in some immune system targets as biomarkers of radioresistance in patients with non-metastatic rectal cancer.METHODSGene expression (GSE68204, GPL6480, and GSE15781) and DNA methylation profiles (GSE75548 and GSE139404) of rectal cancer patients were obtained from the Gene Expression Omnibus (GEO) database. GEO2R and FunRich software were first used to identify genes with significant expression differences. Enricher softwer was then used to analyze Gene Ontology and detect pathway enrichment of hub genes. Blood samples were then taken from 43 rectal cancer patients. After cfDNA extraction from samples, it was treated with bisulfite and analyzed by methylation-specific PCR.RESULTS1088 genes with high and 629 with low expression were identified by GEO2R and FunRich software. A total of five high-expression hub genes, including CDH24, FGF18, CCND1, IFITM1, UBE2V1, and three low-expression hub genes, including CBLN2, VIPR2, and IRF4, were identified from UALCAN and DNMIVD databases. Methylation-specific PCR indicated a significant difference in hub gene methylation between cancerous and non-cancerous individuals. Radiochemotherapy significantly affected hub gene methylation. There was a considerable difference in the methylation rate of hub genes between patients who responded to radiochemotherapy and those who did not.CONCLUSIONSEvaluating gene methylation patterns might be an appropriate diagnostic tool to predict radiochemotherapy response and develop targeted therapeutic agents.

2024-06-01·Molecular and Biochemical Parasitology

Formation of functional E3 ligase complexes with UBC2 and UEV1 of Leishmania mexicana

Article

作者: Geoghegan, Vincent ; Jameson, Katie H ; Dowle, Adam A ; Burge, Rebecca J ; Wilkinson, Anthony J ; Mottram, Jeremy C

In eukaryotic cells, molecular fate and cellular responses are shaped by multicomponent enzyme systems which reversibly attach ubiquitin and ubiquitin-like modifiers to target proteins. The extent of the ubiquitin proteasome system in Leishmania mexicana and its importance for parasite survival has recently been established through deletion mutagenesis and life-cycle phenotyping studies. The ubiquitin conjugating E2 enzyme UBC2, and the E2 enzyme variant UEV1, with which it forms a stable complex in vitro, were shown to be essential for the differentiation of promastigote parasites to the infectious amastigote form. To investigate further, we used immunoprecipitation of Myc-UBC2 or Myc-UEV1 to identify interacting proteins in L. mexicana promastigotes. The interactome of UBC2 comprises multiple ubiquitin-proteasome components including UEV1 and four RING E3 ligases, as well as potential substrates predicted to have roles in carbohydrate metabolism and intracellular trafficking. The smaller UEV1 interactome comprises six proteins, including UBC2 and shared components of the UBC2 interactome consistent with the presence of intracellular UBC2-UEV1 complexes. Recombinant RING1, RING2 and RING4 E3 ligases were shown to support ubiquitin transfer reactions involving the E1, UBA1a, and UBC2 to available substrate proteins or to unanchored ubiquitin chains. These studies define additional components of a UBC2-dependent ubiquitination pathway shown previously to be essential for promastigote to amastigote differentiation.

项与 UBE2V1 相关的新闻（医药）

2023-11-25

·生物制药小编

4大类Toll样受体和免疫通路

Toll样受体(TLR)在触发先天性和适应性免疫反应中发挥着至关重要的作用。它们不仅启动先天免疫反应，而且还是先天免疫和适应性免疫之间的重要连接器。 Toll样受体(TLR)可分为十个，除了TLR10与其他不同，被认为是Toll样信号传导的免疫调节剂。特异性免疫可分为四类，涉及不同的TLR组合。BiomedicinesTH1免疫反应TH1免疫反应是对抗细胞内细菌、原生动物和真菌的宿主免疫反应，涉及的免疫细胞包括M1样巨噬细胞、产生IFN-γ的CD4+ T细胞、细胞毒性CD8+ T细胞和iNKT1等。Biomedicines涉及TH1免疫通路的自身免疫性疾病包括1型糖尿病、多发性硬化症、接触性皮炎和结核病等。关键TLR：TLR7、TLR8和TLR9这三者都位于巨噬细胞的内体区室中。TLR7、TLR8 和 TLR9对应的配体分别是单链RNA、细菌核糖体RNA和未甲基化的CpG DNA寡核苷酸。这些配体是在巨噬细胞吞噬溶酶体中细菌或原生动物的消化过程中产生的。TLR7、TLR8和TLR9主要的信号通路涉及IRF5和IRF7，它们上调IL-12和IFN-γ等下游靶标。TLR8信号转导激活IRF5，而TLR7/9信号转导激活IRF7。TLR7和TLR9首先激活MyD88复合物，包含TRAF3、TRAF6、IRAK4、IRAK1、IKKα、OPNi 和 DOCK2等等。其激活顺序为：TLR7通过激活MyD88从而首先激活IRAK1，再影响IKKα，使其触发转录因子IRF7。IRF7也可以被IRAK1磷酸化。TLR8则通过激活MyD88首先激活TAK1，再影响IKKβ。TAK1还可以激活下游分子JNK。当IKKβ易位到细胞核中时，它会触发转录因子IRF5。IRF5和IRF7的协同作用以产生IL-12，从而引发TH1反应，上调IFN-γ。TH2免疫反应TH2免疫反应是应对寄生虫的免疫反应，分为TH2a和TH2b。TH2a涉及炎性嗜酸性粒细胞、产生IL-4/5的CD4 T 细胞、具有类胰蛋白酶活性(MCt)的肥大细胞、iNKT2细胞和IgG4 B细胞。BiomedicinesTh2b则涉及嗜碱性粒细胞、产生IL-13/4的CD4 T细胞、具有类胰蛋白酶/糜酶活性的肥大细胞(MCtc)、iNKT2 细胞和产生IgE的B细胞。BiomedicinesTH2免疫与1型IgE相关的过敏性疾病密切有关，如哮喘、过敏性鼻炎和特应性皮炎等。关键TLR：TLR1、TLR2和TLR6TLR2和TLR6在嗜碱性粒细胞或肥大细胞等APC的表面上表达。TLR2可以在细胞表面与TLR6或TLR1形成异二聚体，共同识别三酰基脂蛋白，从而触发MAL接头分子，其激活MyD88非依赖性通路，产生IL-4，触发TH2免疫反应。TLR2-TLR6异二聚体则激活下游PI3K和AKT通路。TLR2激活导致TPL2(MAP3K8)被激活，继而通过IKK2介导激活NFκB通路。TPL2还激活MEK1/2和ERK1/2信号转导，从而触发TH2免疫通路。除了IL-4之外，依赖TLR6而上调的IL-25和依赖TLR1/TLR6的IL-33也是驱动TH2免疫反应的关键细胞因子。Th22免疫反应Th22免疫代表宿主针对细胞外细菌、原生动物和真菌的免疫反应。涉及中性粒细胞N1、分泌IL-22的Th细胞、iNKT17细胞和IgG2 B细胞。BiomedicinesTH22主导的免疫通路与3型免疫复合物超敏反应有关，包括阿瑟氏反应和类风湿性关节炎等疾病。关键TLR：TLR2、TLR4和TLR5与TH22免疫通路相关的主要TLR是TLR2、TLR4和TLR5，在中性粒细胞、树突状细胞和单核细胞/巨噬细胞的表面表达。TLR2同型二聚糖可识别革兰氏阳性细菌细胞壁中的肽聚糖和脂磷壁酸，同时还与真菌细胞壁中的β-葡聚糖相互作用。TLR4则负责识别革兰氏阴性菌细胞壁中的 LPS 内毒素。此外，TLR5可识别在运动细菌中发现的鞭毛蛋白。TLR4 信号转导触发MyD88、IRAK1和IRAK4组成的复合物。IRAK4激活IRAK1导致IRAK1自磷酸化及其与MyD88复合物的解离。随后，IRAK1 与泛素结合酶UBC13和UEV1A结合，促进TRAF63/TAK6复合物的泛素化。IRAK1的激活也会诱导TAK1和TRAF6激活，诱导下游NFκB易位到细胞核中，从而触发炎症基因的表达，上调IL-1、IL-6和TNF-α。此外，TAK1激活也导致转录因子AP1依赖于MAPK的激活。Thαβ免疫反应THαβ免疫是宿主针对病毒和朊病毒等传染性分子的免疫反应，涉及NK1细胞、分泌IL-10的CD4 T细胞、iNKT10细胞、CD8 T细胞和IgG1 B细胞。BiomedicinesTHαβ 免疫与2型抗体依赖性细胞毒性超敏反应有关。涉及THαβ免疫通路的自身免疫性疾病包括Graves病、重症肌无力和系统性红斑狼疮等。关键TLR：TLR3、TLR7和TLR9TLR3、TLR7和TLR9主要在浆细胞样树突状细胞的内体区室中表达，内体区室为病毒和 TLR 之间的相互作用提供了理想的环境。TLR3可识别病毒复制过程中产生的dsRNA，而TLR7可检测该阶段也存在的ssRNA。TLR9则可识别在细菌和病毒基因组中未甲基化的CpG DNA。涉及TLR3、TLR7和TLR9的信号通路汇聚在IRF3和IRF7上，启动下游1型IFN信号通路，从而启动THαβ免疫应答。激活后，TLR3直接触发TRIF-IRF3信号通路，TLR7和TLR9激活IRAK1-IRF7信号通路。TRIF-IRF3信号通路触发涉及TRAF3、TBK1和IKKε的级联反应。另一方面，TLR7和TLR9激活MyD88通路，通过IRAK1进一步激活IKKα，在细胞核激活转录因子IRF7。IRF3和IRF7均能激活IFN-α和IFN-β的产生，从而启动THαβ免疫应答。此外，IL-27和IL-10也是驱动细胞因子之一。小结TLR不仅可以通过拮抗剂来治疗自身免疫性疾病，在其他领域也有应用。例如TLR激动剂可用于触发宿主对癌症的免疫反应，诱导癌细胞凋亡，从而作为肿瘤治疗的辅助药物。在疫苗开发中，配方里增加TLR激动剂也可以加强疫苗对致病原的效力。参考文献：1.Chu, Y.-T.; Liao, M.-T.; Tsai, K.-W.; Lu, K.-C.; Hu, W.-C. Interplay of Chemokines Receptors, Toll-like Receptors, and Host Immunological Pathways. Biomedicines 2023, 11, 2384. https://doi-org.libproxy1.nus.edu.sg/10.3390/biomedicines110923842.Jang YH, Choi JK, et al.House Dust Mite Increases pro-Th2 Cytokines IL-25 and IL-33 via the Activation of TLR1/6 Signaling. J Invest Dermatol. 2017 Nov;137(11):2354-2361. doi: 10.1016/j.jid.2017.03.042.

免疫疗法临床1期