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更新于：2025-05-07

TRABD2A

更新于：2025-05-07

基本信息

别名

C2orf89、Metalloprotease TIKI1、TIKI1

+ [3]

简介

Metalloprotease that acts as a negative regulator of the Wnt signaling pathway by mediating the cleavage of the 8 N-terminal residues of a subset of Wnt proteins. Following cleavage, Wnt proteins become oxidized and form large disulfide-bond oligomers, leading to their inactivation. Able to cleave WNT3A, WNT5, but not WNT11. Required for head formation.

关联

项与 TRABD2A 相关的药物

CN118580360

专利挖掘

靶点

TRABD2A

作用机制-

在研机构

中国医科大学附属第一医院

原研机构

中国医科大学附属第一医院

在研适应症

感染

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 TRABD2A 相关的临床结果

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100 项与 TRABD2A 相关的转化医学

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0 项与 TRABD2A 相关的专利（医药）

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项与 TRABD2A 相关的文献（医药）

2023-01-01·Frontiers in cardiovascular medicine

Whole-Exome sequencing analysis identified TMSB10/TRABD2A locus to be associated with carfilzomib-related cardiotoxicity among patients with multiple myeloma.

Article

作者: Cornell, Robert F ; Algubelli, Raghunandan Reddy ; Baz, Rachid C ; Fradley, Michael G ; Shain, Kenneth H ; Tantawy, Marwa ; Gong, Yan ; Siegel, Erin M ; Rubinstein, Samuel M ; Silva, Ariosto S ; Yang, Guang ; Hampton, Oliver A ; Lenihan, Daniel ; DeAvila, Gabriel

BackgroundProteasome inhibitor Carfilzomib (CFZ) is effective in treating patients with refractory or relapsed multiple myeloma (MM) but has been associated with cardiovascular adverse events (CVAE) such as hypertension, cardiomyopathy, and heart failure. This study aimed to investigate the contribution of germline genetic variants in protein-coding genes in CFZ-CVAE among MM patients using whole-exome sequencing (WES) analysis.MethodsExome-wide single-variant association analysis, gene-based analysis, and rare variant analyses were performed on 603,920 variants in 247 patients with MM who have been treated with CFZ and enrolled in the Oncology Research Information Exchange Network (ORIEN) at the Moffitt Cancer Center. Separate analyses were performed in European Americans and African Americans followed by a trans-ethnic meta-analysis.ResultsThe most significant variant in the exome-wide single variant analysis was a missense variant rs7148 in the thymosin beta-10/TraB Domain Containing 2A (TMSB10/TRABD2A) locus. The effect allele of rs7148 was associated with a higher risk of CVAE [odds ratio (OR) = 9.3 with a 95% confidence interval of 3.9-22.3, p = 5.42*10^-7]. MM patients with rs7148 AG or AA genotype had a higher risk of CVAE (50%) than those with GG genotype (10%). rs7148 is an expression quantitative trait locus (eQTL) for TRABD2A and TMSB10. The gene-based analysis also showed TRABD2A as the most significant gene associated with CFZ-CVAE (p = 1.06*10^-6).ConclusionsWe identified a missense SNP rs7148 in the TMSB10/TRABD2A as associated with CFZ-CVAE in MM patients. More investigation is needed to understand the underlying mechanisms of these associations.

2021-12-01·Cancer Prevention Research3区 · 医学

Transcriptome-wideIn VitroEffects of Aspirin on Patient-derived Normal Colon Organoids

3区 · 医学

Article

作者: Kedrin, Dmitriy ; Moreno, Victor ; Dampier, Christopher H. ; Casey, Graham ; Bryant, Jennifer ; Drew, David A. ; Plummer, Sarah J. ; Peters, Ulrike ; Devall, Matthew A.M. ; Ali, Mourad W. ; Zerjav, Dylan C. ; Mo, Jiancheng ; Jennelle, Lucas T. ; Eaton, Stephen ; Powell, Steven M. ; Chan, Andrew T. ; Díez-Obrero, Virginia ; Takacsi-Nagy, Oliver ; Yilmaz, Ömer H.

AbstractMechanisms underlying aspirin chemoprevention of colorectal cancer remain unclear. Prior studies have been limited because of the inability of preclinical models to recapitulate human normal colon epithelium or cellular heterogeneity present in mucosal biopsies. To overcome some of these obstacles, we performed in vitro aspirin treatment of colon organoids derived from normal mucosal biopsies to reveal transcriptional networks relevant to aspirin chemoprevention. Colon organoids derived from 38 healthy individuals undergoing endoscopy were treated with 50 μmol/L aspirin or vehicle control for 72 hours and subjected to bulk RNA sequencing. Paired regression analysis using DESeq2 identified differentially expressed genes (DEG) associated with aspirin treatment. Cellular composition was determined using CIBERSORTx. Aspirin treatment was associated with 1,154 significant (q < 0.10) DEGs prior to deconvolution. We provide replication of these findings in an independent population-based RNA-sequencing dataset of mucosal biopsies (BarcUVa-Seq), where a significant enrichment for overlap of DEGs was observed (P < 2.2E−16). Single-cell deconvolution revealed changes in cell composition, including a decrease in transit-amplifying cells following aspirin treatment (P = 0.01). Following deconvolution, DEGs included novel putative targets for aspirin such as TRABD2A (q = 0.055), a negative regulator of Wnt signaling. Weighted gene co-expression network analysis identified 12 significant modules, including two that contained hubs for EGFR and PTGES2, the latter being previously implicated in aspirin chemoprevention. In summary, aspirin treatment of patient-derived colon organoids using physiologically relevant doses resulted in transcriptome-wide changes that reveal altered cell composition and improved understanding of transcriptional pathways, providing novel insight into its chemopreventive properties.Prevention Relevance:Numerous studies have highlighted a role for aspirin in colorectal cancer chemoprevention, though the mechanisms driving this association remain unclear. We addressed this by showing that aspirin treatment of normal colon organoids diminished the transit-amplifying cell population, inhibited prostaglandin synthesis, and dysregulated expression of novel genes implicated in colon tumorigenesis.

2020-02-14·Journal of Virology

Inhibition of Metalloprotease TRABD2A Facilitates the Study of HIV-1 Replication in Resting CD4 ⁺ T Cells

Letter

作者: Liang, Guoxin ; Dong, Jinxiu ; Shang, Hong

A review on inhibition of metalloprotease TRABD2A facilitates the study of HIV-1 replication in resting CD4+ T cells.It aims to examine the effectiveness of studying HIV-1 replication in resting CD4+ T cells by inhibiting TRABD2A.The depletion of other candidate proteins did not affect the production or infectivity of progeny virions significantly, indicating that none were involved in HIV-1 replication.

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