更新于：2024-05-01

UBA52

ubiquitin A-52 residue ribosomal protein fusion product 1

更新于：2024-05-01

基本信息

别名

60S ribosomal protein L40、CEP52、HUBCEP52

+ [11]

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. Component of the 60S subunit of the ribosome (PubMed:23169626, PubMed:23636399, PubMed:32669547). Ribosomal protein L40 is essential for translation of a subset of cellular transcripts, and especially for cap-dependent translation of vesicular stomatitis virus mRNAs (PubMed:23169626, PubMed:23636399, PubMed:32669547).

关联

100 项与 UBA52 相关的临床结果

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100 项与 UBA52 相关的转化医学

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0 项与 UBA52 相关的专利（医药）

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185

项与 UBA52 相关的文献（医药）

2024-02-09·Journal of biomolecular structure & dynamics

A comprehensive bioinformatics analysis identifies mitophagy biomarkers and potential Molecular mechanisms in hypertensive nephropathy.

Article

作者: Jiayou Liu ; Luda Feng ; Qi Jia ; Jia Meng ; Yun Zhao ; Lei Ren ; Ziming Yan ; Manrui Wang ; Jianguo Qin

Mitophagy, the selective removal of damaged mitochondria, plays a critical role in kidney diseases, but its involvement in hypertensive nephropathy (HTN) is not well understood. To address this gap, we investigated mitophagy-related genes in HTN, identifying potential biomarkers for diagnosis and treatment. Transcriptome datasets from the Gene Expression Omnibus database were analyzed, resulting in the identification of seven mitophagy related differentially expressed genes (MR-DEGs), namely PINK1, ULK1, SQSTM1, ATG5, ATG12, MFN2, and UBA52. Further, we explored the correlation between MR-DEGs, immune cells, and inflammatory factors. The identified genes demonstrated a strong correlation with Mast cells, T-cells, TGFβ3, IL13, and CSF3. Machine learning techniques were employed to screen important genes, construct diagnostic models, and evaluate their accuracy. Consensus clustering divided the HTN patients into two mitophagy subgroups, with Subgroup 2 showing higher levels of immune cell infiltration and inflammatory factors. The functions of their proteins primarily involve complement, coagulation, lipids, and vascular smooth muscle contraction. Single-cell RNA sequencing revealed that mitophagy was most significant in proximal tubule cells (PTC) in HTN patients. Pseudotime analysis of PTC confirmed the expression changes observed in the transcriptome. Intercellular communication analysis suggested that mitophagy might regulate PTC's participation in intercellular crosstalk. Notably, specific transcription factors such as HNF4A, PPARA, and STAT3 showed strong correlations with mitophagy-related genes in PTC, indicating their potential role in modulating PTC function and influencing the onset and progression of HTN. This study offers a comprehensive analysis of mitophagy in HTN, enhancing our understanding of the pathogenesis, diagnosis, and treatment of HTN.Communicated by Ramaswamy H. Sarma.

2024-01-02·BMC genomics

Single-cell and transcriptomic analyses reveal the influence of diabetes on ovarian cancer.

Article

作者: Zhihao Zhao ; Qilin Wang ; Fang Zhao ; Junnan Ma ; Xue Sui ; Hyok Chol Choe ; Peng Chen ; Xue Gao ; Lin Zhang

BACKGROUND:

There has been a significant surge in the global prevalence of diabetes mellitus (DM), which increases the susceptibility of individuals to ovarian cancer (OC). However, the relationship between DM and OC remains largely unexplored. The objective of this study is to provide preliminary insights into the shared molecular regulatory mechanisms and potential biomarkers between DM and OC.

METHODS:

Multiple datasets from the GEO database were utilized for bioinformatics analysis. Single cell datasets from the GEO database were analysed. Subsequently, immune cell infiltration analysis was performed on mRNA expression data. The intersection of these datasets yielded a set of common genes associated with both OC and DM. Using these overlapping genes and Cytoscape, a protein‒protein interaction (PPI) network was constructed, and 10 core targets were selected. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were then conducted on these core targets. Additionally, advanced bioinformatics analyses were conducted to construct a TF-mRNA-miRNA coregulatory network based on identified core targets. Furthermore, immunohistochemistry staining (IHC) and real-time quantitative PCR (RT-qPCR) were employed for the validation of the expression and biological functions of core proteins, including HSPAA1, HSPA8, SOD1, and transcription factors SREBF2 and GTAT2, in ovarian tumors.

RESULTS:

The immune cell infiltration analysis based on mRNA expression data for both DM and OC, as well as analysis using single-cell datasets, reveals significant differences in mononuclear cell levels. By intersecting the single-cell datasets, a total of 119 targets related to mononuclear cells in both OC and DM were identified. PPI network analysis further identified 10 hub genesincludingHSP90AA1, HSPA8, SNRPD2, UBA52, SOD1, RPL13A, RPSA, ITGAM, PPP1CC, and PSMA5, as potential targets of OC and DM. Enrichment analysis indicated that these genes are primarily associated with neutrophil degranulation, GDP-dissociation inhibitor activity, and the IL-17 signaling pathway, suggesting their involvement in the regulation of the tumor microenvironment. Furthermore, the TF-gene and miRNA-gene regulatory networks were validated using NetworkAnalyst. The identified TFs included SREBF2, GATA2, and SRF, while the miRNAs included miR-320a, miR-378a-3p, and miR-26a-5p. Simultaneously, IHC and RT-qPCR reveal differential expression of core targets in ovarian tumors after the onset of diabetes. RT-qPCR further revealed that SREBF2 and GATA2 may influence the expression of core proteins, including HSP90AA1, HSPA8, and SOD1.

CONCLUSION:

This study revealed the shared gene interaction network between OC and DM and predicted the TFs and miRNAs associated with core genes in monocytes. Our research findings contribute to identifying potential biological mechanisms underlying the relationship between OC and DM.

2024-01-01·Journal of pharmaceutical analysis

Hydralazine represses Fpn ubiquitination to rescue injured neurons via competitive binding to UBA52.

Article

作者: Shengyou Li ; Xue Gao ; Yi Zheng ; Yujie Yang ; Jianbo Gao ; Dan Geng ; Lingli Guo ; Teng Ma ; Yiming Hao ; Bin Wei ; Liangliang Huang ; Yitao Wei ; Bing Xia ; Zhuojing Luo ; Jinghui Huang

A major impedance to neuronal regeneration after peripheral nerve injury (PNI) is the activation of various programmed cell death mechanisms in the dorsal root ganglion. Ferroptosis is a form of programmed cell death distinguished by imbalance in iron and thiol metabolism, leading to lethal lipid peroxidation. However, the molecular mechanisms of ferroptosis in the context of PNI and nerve regeneration remain unclear. Ferroportin (Fpn), the only known mammalian nonheme iron export protein, plays a pivotal part in inhibiting ferroptosis by maintaining intracellular iron homeostasis. Here, we explored in vitro and in vivo the involvement of Fpn in neuronal ferroptosis. We first delineated that reactive oxygen species at the injury site induces neuronal ferroptosis by increasing intracellular iron via accelerated UBA52-driven ubiquitination and degradation of Fpn, and stimulation of lipid peroxidation. Early administration of the potent arterial vasodilator, hydralazine (HYD), decreases the ubiquitination of Fpn after PNI by binding to UBA52, leading to suppression of neuronal cell death and significant acceleration of axon regeneration and motor function recovery. HYD targeting of ferroptosis is a promising strategy for clinical management of PNI.

项与 UBA52 相关的新闻（医药）

2024-03-29

·PRNewswire

Journal of Pharmaceutical Analysis (JPA) Studies Find Promising Drug Candidates

Researchers investigate the intricacies of various cellular processes and pathologies and identify compounds with untapped therapeutic potential XI'AN, China, March 29, 2024 /PRNewswire/ -- Understanding the underlying mechanisms of normal and pathological cellular processes is essential for developing new drugs. Fortunately, modern techniques and experimental methods have greatly accelerated progress. The latest issue of JPA features three articles in which candidate compounds for treating complex disorders were successfully identified, alongside their detailed mechanisms of action. Continue Reading Recent JPA studies identify, through detailed analyses of molecular mechanisms and cellular processes, three potential drug candidates for three different pathologies. The first study investigated the use of metformin (Met), a drug used to manage type II diabetes, for treating benign prostate hyperplasia (BPH). The article was published in Volume 14, Issue 1 of the journal in January 2024. The researchers first sought to shed light on how and which dysregulated sex steroid hormone-related pathways shape the pathological characteristics of BPH, and whether Met can restore these pathways. Through retrospective analysis of data from BPH patients and clinical assessment of serum and tissue samples, the researchers identified dihydrotestosterone (DHT) as a major contributor to BPH among dysregulated sex hormones. DHT promotes prostate cell proliferation by upregulating androgen receptors and forming YAP1-TEAD4 heterodimers. In vivo experiments showed that Met treatment restored sex hormone homeostasis and inhibited DHT-induced cell proliferation. "Our study provided strong evidence that Met might be a promising clinical therapeutic approach for the treatment of BPH," remark corresponding authors Prof. Qian Lu and Prof. Xiaoxing Yin. In the second study, scientists explored the role of epimedin B (EB), the main flavonoid in the Chinese herb Epimedium brevicornum Maxim., in melanogenesis. They expanded on previous findings showing EB's ability to induce melanogenesis and activate tyrosinase family of proteins (TYRs). Through comprehensive in vitro and in vivo experiments on human and animal cells, they uncovered how EB modulated TYRs, increased melanosome numbers, promoted maturation, and aided depigmentation and repigmentation. "Our data reveals that EB can stimulate the pigmentation function of TYRs, which might provide a novel rational strategy for hypopigmentation treatment in the pharmaceutical and cosmetic industries," comments corresponding authors Dr. Yiming Li and Prof. Huali Wu. Finally, in the third study, researchers investigated ferroptosis, a type of programmed cell death, and its role in nerve regeneration after peripheral nerve injury (PNI). They found that oxidative stress at the injury site not only triggered both apoptosis and ferroptosis in nearby neurons by increasing intracellular iron via the degradation of ferroportin by UBA52. Using the Drug Signatures Database, they identified hydralazine (HYD), a potent arterial vasodilator, as a potential UBA52 disruptor. Early HYD administration after PNI in vivo expedited axon regeneration and motor function recovery, partly by suppressing ferroptosis. "The potential clinical implementation of HYD may lead to a reduction in the prevalence of individuals with mild symptoms of nerve damage, consequently mitigating the societal burden," conclude corresponding authors Dr. Bing Xia, Prof. Zhuojing Luo, and Dr. Jinghui Huang. Further studies will hopefully clarify the intricate connections among cellular processes, diseases, and potential drugs, paving the way for precise and efficient therapies. Reference Titles of original papers Metformin: A promising clinSical therapeutical approach for BPH treatment via inhibiting dysregulated steroid hormones-induced prostatic epithelial cells proliferation Epimedin B exhibits pigmentation by increasing tyrosinase family proteins expression, activity, and stability Hydralazine represses Fpn ubiquitination to rescue injured neurons via competitive binding to UBA52 Journal: Journal of Pharmaceutical Analysis DOI 1. 2. 3. Media contact Mengjie Wang [email protected] +86-(0)29-88960092 SOURCE Journal of Pharmaceutical Analysis (JPA)