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更新于：2025-05-07

TRIM58

更新于：2025-05-07

基本信息

别名

BIA2、E3 ubiquitin-protein ligase TRIM58、Protein BIA2

+ [4]

简介

E3 ubiquitin ligase induced during late erythropoiesis. Directly binds and ubiquitinates the intermediate chain of the microtubule motor dynein (DYNC1LI1/DYNC1LI2), stimulating the degradation of the dynein holoprotein complex. May participate in the erythroblast enucleation process through regulation of nuclear polarization.

关联

项与 TRIM58 相关的药物

TRIM-473

靶点

TRIM58

作用机制

TRIM58 inhibitors

在研机构

Novartis Institutes for Biomedical Research, Inc.

原研机构

Novartis Institutes for Biomedical Research, Inc.

在研适应症

肿瘤

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 TRIM58 相关的临床结果

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100 项与 TRIM58 相关的转化医学

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0 项与 TRIM58 相关的专利（医药）

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项与 TRIM58 相关的文献（医药）

2025-05-01·Travel Medicine and Infectious Disease

Transcriptomic analysis of chronic chikungunya in the Reunionese CHIKGene cohort uncovers a shift in gene expression more than 10 years after infection

Article

作者: Meyniel, Jean-Philippe ; Medina-Santos, Raissa ; Savara, Jakub ; Noirel, Josselin ; Cornet, Clémence ; Hocini, Hakim ; Ah-You, Nathalie ; Gérardin, Patrick ; Lefebvre, Cécile ; Maillot, Adrien ; Labib, Taoufik ; Payet, Christine ; El Jahrani, Nora ; Zagury, Jean-François ; Mussard, Corinne ; Rahmouni, Myriam ; Fontaine, Christine ; Porcherat, Sylvaine ; Le Clerc, Sigrid ; Marimoutou, Catherine ; Spadoni, Jean-Louis ; Bruneau, Léa ; Mathew, Mano Joseph ; Medjane, Samir ; Chabert, Cécile

AIMIn 2005-2006, a chikungunya epidemic of unprecedented magnitude hit Reunion Island, which raised a public health concern through the substantial proportions of long-lasting manifestations. To understand the pathophysiology underlying chronic chikungunya (CC), we designed the CHIKGene cohort study and collected blood samples from 133 subjects diagnosed with CC and from 86 control individuals that had recovered within 3 months, 12-to-15 years after exposure.METHODSWe conducted bulk RNAseq analysis on peripheral blood mononuclear cells to find differentially expressed genes (DEGs), gene set enrichment analysis (GSEA) and gene ontologies to uncover top-level enriched terms associated with DEGs, and weighted gene correlation network analysis (WGCNA) to elucidate underlying cellular processes.RESULTSAmong 1549 DEGs, gene expression analysis identified 10 top genes including NR4A2 and TRIM58 (upregulated in CC), IGHG3 and IGHV3-49 (downregulated in CC) linked to immune regulation, OSBP2 (upregulated in CC) and SEMA6B (downregulated in CC) linked to neuronal homeostasis and axon guidance, respectively. GSEA and WGCNA unveiled cellular processes such as "Metabolism of RNA" and "Cell Cycle".CONCLUSIONSThis study uncovers a shift in gene expression of CC subjects. IGHG3 and IGHV3-49 gene shut-offs spotlight the importance of neutralizing antibodies against chikungunya virus in the progression to chronic disease. Human diseases associations highlight connections to rheumatoid arthritis, nervous and cardiac systems. GSEA and WGCNA bounce the hypotheses of a persistent viral reservoir or an increased susceptibility to RNA viral pathogens with new onset infections. Together, our findings might offer potential targets for therapeutic options aimed at alleviating chronic chikungunya.

2025-03-01·Anti-Cancer Drugs

Comprehensive analysis of DNA methylation and gene expression to identify tumor suppressor genes reactivated by MLN4924 in acute myeloid leukemia

Article

作者: Liu, Bei ; Jian, Jinli ; Zhao, Long ; Tang, Xiao ; Guo, Yuancheng

This study investigated whether the neddylation inhibitor MLN4924 induces aberrant DNA methylation patterns in acute myeloid leukemia and contributes to the reactivation of tumor suppressor genes. DNA methylation profiles of Kasumi-1 and KU812 acute myeloid leukemia cell lines before and after MLN4924 treatment were generated using the 850K Methylation BeadChip. RNA sequencing was used to obtain transcriptomic profiles of Kasumi-1 cells. Target genes were identified through a combined analysis of methylation and transcriptome data. Methylation-specific PCR and quantitative PCR validated the changes in methylation and expression. Prognostic analysis of target genes was performed using databases, and Pearson correlation was used to examine the relationship between methylation and expression levels. In Kasumi-1 and KU812 cells, 301 and 469 differentially methylated sites, respectively, were identified. A total of 4310 differential expression genes were detected in Kasumi-1. Combined analysis revealed that TRIM58 exhibited significant demethylation and upregulation after MLN4924 treatment, as confirmed by quantitative and methylation-specific PCR. Furthermore, database analysis revealed that both down-expression and promoter hypermethylation of TRIM58 were correlated with poor prognosis in acute myeloid leukemia. A negative correlation was observed between TRIM58 methylation and expression levels. This study suggests that MLN4924 alters DNA methylation patterns in acute myeloid leukemia and reactivates TRIM58, a potential tumor suppressor gene, through demethylation.

2025-01-01·Journal of Biological Chemistry

Redirecting E3 ubiquitin ligases for targeted protein degradation with heterologous recognition domains

Article

作者: Orkin, Stuart H ; Yang, Huan ; Alshaye, Alia ; Li, Grace Y ; Zheng, Ge

Targeted protein degradation (TPD) mediated by proteolysis targeting chimeras or molecular glues is an emerging therapeutic strategy. Despite greater than 600 E3 ligases and their associated components, a limited number have been deployed in TPD. Those commonly used include cereblon and von Hippel-Lindau tumor suppressor (VHL), which is expressed widely and for which high affinity ligands are available. Limiting TPD to specific cells or tissues would be desirable in many settings. To this goal we have determined the potential of two erythroid cell-enriched E3 ligases, TRIM10 and TRIM58, to degrade a protein of interest, BCL11A, a validated therapeutic target for the β-hemoglobinopathies. We established a general strategy in which heterologous recognition domains replace the PRY-SPRY domain of TRIM10 and TRIM58. Recruitment of TRIM10 or TRIM58 to BCL11A by coiled-coil peptides, nanobodies, or the substrate recognition domain of cereblon led to its degradation. Our findings illustrate a strategy that may be widely useful in evaluating the TPD potential of other E3 ubiquitin ligases and provide a rationale for discovery of ligands for TRIM10 and TRIM58 for erythroid-selective depletion of proteins of interest.

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