预约演示

更新于：2025-05-07

UBB

更新于：2025-05-07

基本信息

别名

FLJ25987、MGC8385、Polyubiquitin-B

+ [3]

简介

Exists either covalently attached to another protein, or free (unanchored). When covalently bound, it is conjugated to target proteins via an isopeptide bond either as a monomer (monoubiquitin), a polymer linked via different Lys residues of the ubiquitin (polyubiquitin chains) or a linear polymer linked via the initiator Met of the ubiquitin (linear polyubiquitin chains). Polyubiquitin chains, when attached to a target protein, have different functions depending on the Lys residue of the ubiquitin that is linked: Lys-6-linked may be involved in DNA repair; Lys-11-linked is involved in ERAD (endoplasmic reticulum-associated degradation) and in cell-cycle regulation; Lys-29-linked is involved in proteotoxic stress response and cell cycle; Lys-33-linked is involved in kinase modification; Lys-48-linked is involved in protein degradation via the proteasome; Lys-63-linked is involved in endocytosis, DNA-damage responses as well as in signaling processes leading to activation of the transcription factor NF-kappa-B. Linear polymer chains formed via attachment by the initiator Met lead to cell signaling. Ubiquitin is usually conjugated to Lys residues of target proteins, however, in rare cases, conjugation to Cys or Ser residues has been observed. When polyubiquitin is free (unanchored-polyubiquitin), it also has distinct roles, such as in activation of protein kinases, and in signaling.

关联

项与 UBB 相关的药物

Dual aptamer+UBB siRNA

靶点

UBB x UBC

作用机制

UBB inhibitors [+1]

在研机构

Systems Oncology LLC

原研机构

Systems Oncology LLC

在研适应症

肿瘤

非在研适应症-

最高研发阶段药物发现

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 UBB 相关的临床结果

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100 项与 UBB 相关的转化医学

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0 项与 UBB 相关的专利（医药）

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231

项与 UBB 相关的文献（医药）

2025-02-01·Journal of Applied Genetics

Transcriptome profiling and metabolic pathway analysis towards reliable biomarker discovery in early-stage lung cancer

Article

作者: Karuppasamy, Ramanathan ; Veerappapillai, Shanthi ; Thirunavukkarasu, Muthu Kumar ; Ramesh, Priyanka

Earlier diagnosis of lung cancer is crucial for reducing mortality and morbidity in high-risk patients. Liquid biopsy is a critical technique for detecting the cancer earlier and tracking the treatment outcomes. However, noninvasive biomarkers are desperately needed due to the lack of therapeutic sensitivity and early-stage diagnosis. Therefore, we have utilized transcriptomic profiling of early-stage lung cancer patients to discover promising biomarkers and their associated metabolic functions. Initially, PCA highlights the diversity level of gene expression in three stages of lung cancer samples. We have identified two major clusters consisting of highly variant genes among the three stages. Further, a total of 7742, 6611, and 643 genes were identified as DGE for stages I-III respectively. Topological analysis of the protein-protein interaction network resulted in seven candidate biomarkers such as JUN, LYN, PTK2, UBC, HSP90AA1, TP53, and UBB cumulatively for the three stages of lung cancers. Gene enrichment and KEGG pathway analyses aid in the comprehension of pathway mechanisms and regulation of identified hub genes in lung cancer. Importantly, the medial survival rates up to ~ 70 months were identified for hub genes during the Kaplan-Meier survival analysis. Moreover, the hub genes displayed the significance of risk factors during gene expression analysis using TIMER2.0 analysis. Therefore, we have reason that these biomarkers may serve as a prospective targeting candidate with higher treatment efficacy in early-stage lung cancer patients.

2025-01-01·International Journal of Biometeorology

Chronic heat stress upregulates pyruvate metabolic process and gluconeogenesis but downregulates immune responses in Sahiwal cattle

Article

作者: Gowane, Gopal Ramdasji ; De, Sachinandan ; Khan, Kashif Dawood ; Alex, Rani ; Das, Pradyut ; Ludri, Ashutosh ; Paul, Dipankar ; Vohra, Vikas ; Upadhyay, Amritanshu

Climate change and growing population and their strain on animal production are the impending challenges that the developing countries, like India, need to tackle in the coming days. This study aimed to detect and analyze the uncharacterized variation in the gene expression patterns with the change of condition, from thermoneutral to chronic hot-humid, in the Sahiwal cattle, one of the best breeds of milk-producing cattle in India, known for being heat-tolerant. Using RNA-Seq analysis on peripheral blood mononuclear cells (PBMCs), 4021 differentially expressed mRNAs (2772 upregulated, 1249 downregulated) and 1303 differentially expressed long non-coding RNAs (769 upregulated, 534 downregulated) were identified, with the thresholds of false discovery rate < 0.05 and|log₂(fold change)| > 2. Significantly (p-adjusted < 0.05) overrepresented Gene Ontology (GO) terms, Kyoto Encyclopedia of Genes and Genomes (KEGG), and Reactome pathways were analyzed, revealing upregulation of processes like pyruvate metabolic process, gluconeogenesis, ion transmembrane transport, neuropeptide signaling pathway, and animal organ development, with genes like SHH, GRK1, CHRM3, CAMK2A, and HSPB7 were upregulated, while translation and immune responses, with genes like RPS3, EEF1A1, TNF, BoLA-DRB3, and UBB were downregulated. Analysis of cis-mRNAs of DE-lncRNAs showed presence of both up- and down-regulated cis-mRNAs for both up- and down-regulated lncRNAs indicating existence of positive and negative regulation of mRNA expression by lncRNAs. Managemental nudges that decrease metabolic heat generation, like betaine and chromium supplementation, and increase heat dissipation, like microenvironment cooling, should be utilized. This study highlights the role of pyruvate metabolism and gluconeogenesis in coping up with heat stress and offers an improved understanding of the heat stress response of Sahiwal cattle along with the genes and pathways responsible for it.

2024-11-01·Developmental Dynamics

Rapid generation of single‐insertion transgenics by Tol2 transposition in zebrafish

Article

作者: Kalvaitytė, Miglė ; Balciunas, Darius ; Gabrilavičiūtė, Sofija

AbstractBackgroundThe Tol2 transposable element is the most widely used transgenesis tool in zebrafish. However, its high activity almost always leads to multiple unlinked integrations of the transgenic cassette in F1 fish. Each of these transgenes is susceptible to positional effects from the surrounding regulatory landscape, which can lead to altered expression and, consequently, activity. Scientists therefore must strike a balance between the need to maximize reproducibility by establishing single‐insertion transgenic lines and the need to complete experiments within a reasonable timeframe.ResultsIn this article, we introduce a simple competitive dilution strategy for rapid generation of single‐insertion transgenics. By using cry:BFP reporter plasmid as a competitor, we achieved a nearly fourfold reduction in the number of the transgene of interest integrations while simultaneously increasing the proportion of single‐insertion F1 generation transgenics to over 50%. We also observed variations in transgene of interest expression among independent single‐insertion transgenics, highlighting that the commonly used ubiquitous ubb promoter is susceptible to position effects.ConclusionsWide application of our competitive dilution strategy will save time, reduce animal usage, and improve reproducibility of zebrafish research.

项与 UBB 相关的新闻（医药）

2024-03-14

·今日头条

可抑制癌细胞增殖！哈尔滨医科大学、中国科学技术大学联合发文：揭示癌症治疗新策略

本文为转化医学网原创，转载请注明出处作者：Jerry 导读：透明细胞肾细胞癌(ccRCC)具有独特的特征，即高度的血管生成和强健的血管化。了解这种异质性背后的机制对于开发有效的治疗策略至关重要。 3月11日，哈尔滨医科大学与中国科学技术大学研究人员共同在期刊《Oncogene》上发表了研究论文，题为“Downregulation of UBB potentiates SP1/VEGFA-dependent angiogenesis in clear cell renal cell carcinoma”。本研究中，研究表明泛素B（UBB）过表达显著抑制了肾细胞癌细胞的增殖、肿瘤负荷和体内外血管生成。研究结果证明了UBB在抗血管生成治疗中的关键作用，并揭示了UBB作为ccRCC治疗干预的潜在靶点。 https://www.nature.com/articles/s41388-024-03003-6#Sec9 研究背景 01 透明细胞肾细胞癌是一种常见的肾癌类型，具有侵袭性组织学特征。前期研究表明，肿瘤微环境是ccRCC的重要组成部分，分别在TCGA-KIRC、GSE53000和GSE53757数据库中分别发现了76、105和48个与ccRCC微环境相关的基因，并从这些基因中筛选出肿瘤微环境相关基因UBB。 ccRCC通常具有异质性组织学特征，如富含糖原的细胞质、嗜酸性细胞质、细血管网和增大的厚血管结构。这种异质性主要归因于von Hippel-Lindau(VHL)突变。因此，ccRCC细胞表现出以血管内皮生长因子(VEGF)激活为特征的假性缺氧表型，导致其独特的外观。鉴于在更晚期的ccRCC中观察到广泛的新生血管化，治疗方法主要围绕着使用特异性抑制VEGF的TKIs或单克隆抗体靶向VEGF信号通路。目前，许多TKIs作为转移性肿瘤的主要一线治疗选择，在延长无进展生存期方面表现出显著的疗效。然而，一组患者表现出固有耐药性，大多数患者最终获得耐药性，导致最终死亡结果。因此，需要一种新的抗血管生成治疗方案，作为一种可行的策略来优化治疗效果。然而，UBB是否通过调节ccRCC微环境中的SP1-VEGFA轴来调节血管生成过程仍然不为人所知。研究进展 02 为了研究和验证UBB在体外肿瘤进展中的作用，研究人员使用转染UBB过表达慢病毒(UBB_OE)的肾癌细胞进行了细胞活力，细胞增殖，细胞迁移和细胞侵袭的实验。EdU实验和克隆形成实验结果显示，UBB过表达后肾癌细胞的活力和增殖能力显著降低。此外，通过划痕实验和Transwell实验，研究人员发现UBB过表达抑制了肾癌细胞的迁移和侵袭。研究人员还建立了裸鼠移植瘤模型，以验证UBB在体内的疗效。UBB过表达后，肿瘤生长明显受到抑制。称量肿瘤重量并切片进行病理分析。UBB_OE组Ki67和CD31的表达水平较UBB_NC组明显降低。因此，UBB在ccRCC中起着肿瘤生长抑制基因的作用。另外，通过对生理过程的全面分析，研究人员还揭示了UBB低表达和血管生成激活之间的潜在关联。大量文献表明，血管生成在ccRCC的发生和发展过程中异常激活。本研究结果支持UBB通过诱导VEGFA表达的调节来调节血管生成的观点。 UBB抑制肾癌细胞体外血管生成研究结论 03 总之，本研究揭示了UBB在通过SP1/VEGFA信号阻滞ccRCC生长和血管生成中的重要性。 UBB在增强抗血管生成治疗和克服帕唑帕尼耐药方面的潜力为缓解ccRCC提供了一种有前景的创新策略。参考资料： https://www.nature.com/articles/s41388-024-03003-6#Sec9 注：本文旨在介绍医学研究进展，不能作为治疗方案参考。如需获得健康指导，请至正规医院就诊。热门·直播/活动 🕓 上海｜06月14日-16日 ▶ 第六届上海国际癌症大会将于6月14-16日在上海举办，学科交叉，共同推进肿瘤研究与诊治多模态！ 🕓 北京｜09月20日-21日 ▶ 第五届单细胞技术应用研讨会暨空间组学前沿研讨会欢迎您的参与！点击对应文字查看详情

临床研究临床结果

2023-03-13

·生物谷

《自然·衰老》：全海马单细胞转录组学研究，全面揭示APOE4促进阿尔茨海默病发生机制

阿尔茨海默病（AD）是一种多见于老年人的神经系统退行性疾病。正如影视作品中所描述的这样，随着疾病的进展，患者逐渐忘记周围的人，忘记自己引以为傲的过去，失去丰沛的感情，最终丧失生活能力。阿尔茨海默病（AD）是一种多见于老年人的神经系统退行性疾病。正如影视作品中所描述的这样，随着疾病的进展，患者逐渐忘记周围的人，忘记自己引以为傲的过去，失去丰沛的感情，最终丧失生活能力。而有这样一类人群：APOE4基因的携带者，他们患AD的风险更高，发病也更早 [1]。长期以来，人们对APOE4基因做了大量研究，尝试揭开APOE4推动AD发生发展的秘密。但既往研究大都局限于某一种细胞或者某一条通路，让我们无法对APOE4与AD病理进程的关系建立完整的概念。近期，来自美国加利福尼亚大学的黄亚东教授团队的一项研究，通过记录小鼠大脑内单细胞核转录组学变化，发现敲除神经元内APOE4基因可改善Tau蛋白介导的胶质细胞激活，神经系统脱髓鞘改变和神经元死亡等一系列病理损伤[2]。研究成果发表在《自然•衰老》上。文章首页截图 APOE有三种等位基因，其中APOE4可以大大提高患AD的风险，而APOE2正相反，可以降低AD的发病风险。APOE3被称为野生型，对AD风险增加或减少无明显作用[3]。为了研究APOE4的作用，研究者们将表达loxP序列的人APOE3和APOE4基因的小鼠，与神经元特异性启动子Syn1-Cre小鼠杂交，得到了可以在神经元内特异性敲除APOE基因的小鼠。在此基础上，研究者们将上述模型鼠与Tau蛋白病理模型鼠PS19杂交，得到了四种转基因小鼠模型：PS19-fE3，PS19-fE3/Syn1-Cre，PS19-fE4，PS19-fE4/Syn1-Cre。这样就可以在神经元内存在或不存在APOE基因的情况下观察Tau蛋白病理变化。接下来，研究者们在小鼠10月龄时对海马中Tau蛋白病理进行了检测，实验结果表明，表达APOE4的小鼠海马区域有大量的磷酸化Tau蛋白和神经元纤维缠结。在神经元内特异性敲除APOE4后，磷酸化Tau蛋白的水平下降了81%，含有纤维缠结的神经元数量也明显降低了（P=0.0103）。通过在小鼠右侧海马注射表达P301S突变Tau蛋白的慢病毒载体，研究者们观察到表达APOE4的小鼠左侧海马Tau蛋白病理阳性的神经元数量增加，在神经元内敲除APOE4后有明显改善（P<0.0001）。说明APOE4在Tau蛋白异常磷酸化，Tau蛋白聚集，和Tau蛋白在神经元间传播过程中全部发挥了作用。图a，b: PS19-fE4小鼠中磷酸化Tau和神经纤维缠结较PS19-fE3小鼠明显增加，在神经元中敲除APOE4后下降。图c，d：在右侧海马注射P301S Tau表达载体后，fE4小鼠左侧海马人源性Tau蛋白和磷酸化Tau蛋白均高于敲除组。图e.f：APOE4存在时海马中不可溶性磷酸化Tau蛋白增加。 Tau蛋白病理与AD的进展密切相关，那么，如果在神经元内特异性敲除APOE4是否能改变这一进程呢？研究者们对此一一进行了解答。首先，研究发现PS19-fE4小鼠海马区发生了神经退行性改变,这一组小鼠的海马体积显著缩小，海马CA1区和齿状回的厚度明显变薄，神经元凋亡标志物Caspase-3剪切体表达明显升高（P<0.0001），这说明神经元出现了严重的死亡情况。而PS19-fE3，PS19-fE3/Syn1-Cre和PS19-fE4/Syn1-Cre三组小鼠均未出现明显的神经元死亡情况，说明上述神经退行性改变是由于APOE4存在引起的。图a，b: PS19-fE4小鼠海马体积减小，齿状回厚度降低，敲除神经元APOE4后恢复。图c，d：PS19-fE4小鼠海马出现神经脱髓鞘改变和神经元过度兴奋，敲除神经元APOE4后恢复。在髓鞘损伤的检测中也有类似的发现。研究人员检测了PS19-fE4小鼠海马区髓鞘损伤情况和髓鞘修复情况。结果发现APOE4存在的情况下小鼠髓鞘受损严重。在海马区特异性敲除APOE4后，髓鞘受损情况和损伤修复情况均恢复到了与PS19-fE3小鼠相似的水平。除此之外，研究者们还发现与PS19-fE3小鼠相比，PS19-fE4小鼠CA1-CA3环路过度兴奋，小胶质细胞和星形胶质细胞明显激活。APOE4敲除后这两种现象都得到了缓解。由此可见，神经元内APOE4的敲除减缓了Tau蛋白病理状态下的神经元死亡、神经系统脱髓鞘改变和神经元功能的改变。通过上述结果，我们不难发现，神经元内APOE4的存在不仅影响了神经元本身，还影响了胶质细胞。那么在整个海马区域，是不是所有细胞都受到了这种影响，共同推动了神经退行性改变的进展呢？接下来的实验中，研究者们对PS19-fE3，PS19-fE4，PS19-fE4/Syn1-Cre三组小鼠海马区的细胞进行了单细胞核转录组分析，根据不同的细胞标记基因表达水平变化，将整个海马区的细胞分成了34个类群。根据每群细胞在三组小鼠中数量占比的不同，研究者们将在PS19-fE4小鼠中显著增加的细胞群定义为神经元APOE4介导的疾病相关(nE4-DA)细胞群。图a: 单细胞核转录组分析将海马细胞分为34个亚群。图b: 三组小鼠中不同亚群细胞中APOE表达情况。图c：疾病相关神经元中高表达和低表达的基因。图d：PS19-fE4/Syn1-Cre小鼠与PS19-fE4小鼠相比疾病相关神经元中基因表达的变化情况。在对这些特殊细胞群进行基因表达分析时，研究人员有了令人兴奋的发现。不论什么种类的细胞中，nE4-DA细胞群均高表达Hspa8，Hsp90aa1，Hsp90ab1，Calm1，Calm2，Nrgn和Ubb这几种基因。不仅如此，通过对PS19-fE4/Syn1-Cre小鼠的nE4-DA细胞群进行分析，研究者们发现清除神经元中的APOE4基因后，上述基因表达量降低了。这说明APOE4的清除不仅改变了nE4-DA细胞群的数量，还改变了nE4-DA细胞群的基因表达。这些在APOE4存在情况下高表达的基因，可能就是解开APOE4致病机制之谜的关键。总的来说，本研究重点关注了神经元中APOE4对Tau蛋白病理的推动作用，发现神经元中特异性敲除APOE4可以使海马中的病理性Tau蛋白含量下降81%。尽管神经元中的APOE4如何介导其它细胞的病理变化还有待探索，但本文已经为我们提供了很有利的证据。如果能够找到安全稳定的方法特异性敲除神经元中的APOE4基因，也许能够降低这类人群的患病风险。参考文献： [1] Corder EH, Saunders AM, Strittmatter WJ, et al. Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer's disease in late onset families. Science. 1993;261(5123):921-923. doi:10.1126/science.8346443 [2] Koutsodendris, N., Blumenfeld, J., Agrawal, A. et al. Neuronal APOE4 removal protects against tau-mediated gliosis, neurodegeneration and myelin deficits. Nat Aging (2023). https://doi.org/10.1038/s43587-023-00368-3 [3] Shi Y, Yamada K, Liddelow SA, et al. ApoE4 markedly exacerbates tau-mediated neurodegeneration in a mouse model of tauopathy. Nature. 2017;549(7673):523-527. doi:10.1038/nature24016

临床结果临床1期临床2期