更新于：2024-09-19

UBP1

更新于：2024-09-19

基本信息

别名

LBP-1a、LBP1、Transcription factor LBP-1

+ [3]

简介

Functions as a transcriptional activator in a promoter context-dependent manner. Modulates the placental expression of CYP11A1. Involved in regulation of the alpha-globin gene in erythroid cells. Activation of the alpha-globin promoter in erythroid cells is via synergistic interaction with TFCP2 (By similarity). Involved in regulation of the alpha-globin gene in erythroid cells. Binds strongly to sequences around the HIV-1 initiation site and weakly over the TATA-box. Represses HIV-1 transcription by inhibiting the binding of TFIID to the TATA-box.

关联

100 项与 UBP1 相关的临床结果

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100 项与 UBP1 相关的转化医学

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0 项与 UBP1 相关的专利（医药）

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129

项与 UBP1 相关的文献（医药）

2024-06-01·The Spine Journal

The association of lumbar intervertebral disc degeneration with low back pain is modified by underlying genetic propensity to pain

Article

作者: Williams, Frances M K ; Freidin, Maxim B ; Smith, Isabelle Granville ; Heagerty, Patrick J ; Naeini, Maryam Kazemi ; Tsepilov, Yakov A ; Elgaeva, Elizaveta E ; Suri, Pradeep ; Compte, Roger

BACKGROUND CONTEXTAssociations between magnetic resonance imaging (MRI)-detected lumbar intervertebral disc degeneration (LDD) and LBP are often of modest magnitude. This association may be larger in specific patient subgroups.PURPOSETo examine whether the association between LDD and LBP is modified by underlying genetic predispositions to pain.STUDY DESIGNCross-sectional study in UK Biobank (UKB) and Twins UK.PATIENT SAMPLESA genome-wide association study (GWAS) of the number of anatomical chronic pain locations was conducted in 347,538 UKB participants. The GWAS was used to develop a genome-wide polygenic risk score (PRS) in a holdout sample of 30,000 UKB participants. The PRS model was then used in analyses of 645 TwinsUK participants with standardized LDD MRI assessments.OUTCOME MEASURESEver having had LBP associated with disability lasting ≥1 month (LBP1).METHODSUsing the PRS as a proxy for "genetically-predicted propensity to pain", we stratified TwinsUK participants into PRS quartiles. A "basic" model examined the association between an LDD summary score (LSUM) and LBP1, adjusting for covariates. A "fully-adjusted" model also adjusted for PRS quartile and LSUM x PRS quartile interaction terms.RESULTSIn the basic model, the odds ratio (OR) of LBP1 was 1.8 per standard deviation of LSUM (95% confidence interval [CI] 1.4-2.3). In the fully-adjusted model, there was a statistically significant LSUM-LBP1 association in quartile 4, the highest PRS quartile (OR=2.5 [95% CI 1.7-3.7], p=2.6×10^-6), and in quartile 3 (OR=2.0, [95% CI 1.3-3.0]; p=.002), with small-magnitude and/or nonsignificant associations in the lowest 2 PRS quartiles. PRS quartile was a significant effect modifier of the LSUM-LBP1 association (interaction p≤.05).CONCLUSIONSGenetically-predicted propensity to pain modifies the LDD-LBP association, with the strongest association present in people with the highest genetic propensity to pain. Lumbar MRI findings may have stronger connections to LBP in specific subgroups of people.

2024-04-01·Data in Brief

Proteomic data of the Trypanosoma cruzi insect-dwelling epimastigotes overexpressing the RNA-binding protein UBP1

Article

作者: De Gaudenzi, Javier G ; Sabalette, Karina B ; Campo, Vanina A

We present data on the proteome of the Trypanosoma cruzi epimastigote cells overexpressing the U-rich RNA-binding protein 1 (UBP1). The role of this regulatory protein during the epimastigote-to-metacyclic trypomastigote stage transition was clearly established by our group at the transcriptome level; nevertheless, the impact of UBP1 overexpression on protein synthesis is not known. To address this question, we performed shotgun label-free quantification proteomics using an in vitro system based on the tetracycline-inducible expression of TcUBP1 and epimastigote wildtype cells. Using tryptic peptide digestion and LC-MS/MS analysis with Orbitrap technology, this data file describes the proteome of three biological samples per condition and yields 1637 correctly quantified proteins. The statistical comparisons of the two analyzed groups within the Proteome Discoverer platform identified 379 differentially expressed proteins, with 207 being up-regulated and 172 being down-regulated. In addition, profile plots and heatmap analysis to visualize the distribution of protein abundances within replicates are also presented. Data are available via ProteomeXchange with identifier PXD047761.

2024-04-01·Data in Brief

RNA-seq data exploration after trypanosome RNA-binding protein UBP1 expression is altered by CRISPR-Cas9 gene editing and overexpression

Article

作者: Sotelo-Silveira, José R ; De Gaudenzi, Javier G ; Sabalette, Karina B ; Smircich, Pablo ; Campo, Vanina A

Previous studies have shown that overexpression of the Trypanosoma cruzi U-rich RNA-binding protein 1 (TcUBP1) in insect-dwelling epimastigotes results in a gene expression pattern resembling that of the infective form of the pathogen. Here, we used CRISPR-Cas9-induced edition of TcUBP1 and full-length protein overexpression in epimastigote cells to monitor transcriptomic changes during the epimastigote-to-metacyclic trypomastigote stage transition of T. cruzi. This dataset includes the bioinformatics analysis of three different RNA-seq samples, each with three biological replicates, showing differential mRNA abundances. The current transcriptome report has the potential to shed light on the quantitative variances in the expression of significant up- or down-regulated mRNAs as a consequence of the levels of the UBP1 protein. Raw data files were deposited at the NCBI Sequence Read Archive - SRA at http://ncbi.nlm.nih.gov.libproxy1.nus.edu.sg/Traces/sra/sra.cgi with accession numbers PRJNA907231 and PRJNA949967.

项与 UBP1 相关的新闻（医药）

2024-03-02

·生物探索

Nat Commun | 厦门大学李剑课题组发现疟原虫抗药的新机制

引言疟疾是由疟原虫感染引起的传染性寄生虫病，全球每年有超过2.4亿人感染，造成~60万人死亡。当前，恶性疟原虫几乎对所有类型的抗疟药包括青蒿素及青蒿素类复方药均产生了不同程度的抗性。抗药性疟原虫的出现、演化及蔓延是疟疾防治和根除的主要难题。跨膜转运蛋白MDR1是哺乳类P-gp蛋白的同源物，早期的研究显示MDR1定位于疟原虫的消化泡（digestive vacuole, DV）泡膜。该蛋白可转运不同类型的抗疟药/引起不同的药敏反应而受到耐药性研究领域的广泛关注。然而，调控MDR1亚细胞定位及抗药性发生的机制一直是个谜。2024年2月27日，厦门大学生命科学学院李剑课题组在Nature Communications 发表题为“Deaggregation of mutant Plasmodium yoelii de-ubiquitinase UBP1 alters MDR1 localization to confer multidrug resistance”的研究论文，该研究揭示疟原虫去泛素化酶UBP1突变体通过调节MDR1的泛素化和改变其细胞定位，介导MDR1对多种抗疟药的外排，引起疟原虫产生多重抗药性。研究人员首先通过甲氟喹（mefloquine）筛选、构建遗传杂交和遗传定位，发现约氏疟原虫的UBP1编码基因与抗药表型相连锁，并新发现两个独特的与抗药性相关的点突变I1560N和P2874T（均为疏水性氨基酸突变为亲水性氨基酸），突变位点分别位于CCR和UCH功能结构域。接着研究人员应用基因编辑技术对敏感性虫株（IP单倍型）和抗性虫株（NT单倍型）的ubp1进行一系列单点和双点等位替换，正向及反向替换的药敏测试结果证明在两个位点同时突变的情形下疟原虫具有多重抗药性，即突变体对甲氟喹、苯芴醇（lumefantrine）及哌喹（piperaquine）等抗疟药（常用作青蒿素类复方的伴侣药物）均产生了抗性。深入的表型分析阐明双点突变不仅损坏UBP1去泛素化酶的生理功能，而且显著降低原虫率和消化泡中疟色素的生成。UBP1蛋白含有3100多个氨基酸，分析显示该蛋白序列存在高度的固有无序域（intrinsically disordered region, IDR），提示其可通过相分离形成无膜细胞器或凝聚体。质谱鉴定和免疫印迹研究表明，MDR1是UBP1酶促作用的底物蛋白。机制分析发现，野生型UBP1形成具功能性的点状凝聚体对MDR1进行去泛素化，脱泛素化的MDR1定位于消化泡膜；而突变型UBP1由于IP→NT突变破坏了凝聚体的形成及酶活性，导致MDR1泛素化水平升高，造成MDR1易位至细胞质膜，此时MDR1可将抗疟药泵出胞外以降低胞内的药物浓度，致使疟原虫获得抗性。最后，研究者使用P-gp抑制剂他立喹达（tariquidar）与甲氟喹等进行联合用药，发现组合用药可显著杀灭抗性疟原虫。模式图（Credit: Nature Communications）该研究发现并解析了一种新的疟原虫抗药机制：UBP1位点突变→凝聚体及酶活性受损→泛素化水平升高致使MDR1从消化泡膜易位至细胞质膜→药物外排→抗药性产生。研究结论对于抗药性的监测，抗疟药研发和联合用药有重要的指导意义。原文链接https://www-nature-com.libproxy1.nus.edu.sg/articles/s41467-024-46006-3责编|探索君排版|探索君文章来源|“iNature”End往期精选围观一文读透细胞死亡(Cell Death) | 24年Cell重磅综述（长文收藏版）热文Nature | 破除传统：为何我们需要重新思考肿瘤的命名方式热文Nature | 2024年值得关注的七项技术热文Nature | 自身免疫性疾病能被治愈吗？科学家们终于看到了希望热文Nature | 癌症与神经系统的致命舞蹈