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TAX1BP3 是一种SUMOylated核细胞质穿蛋白,可以防止血管新极性增生

Hanyan Yang^1,2, Yulong Zhong³, Wenjie Guo^1,2

¹Department of Cardiology, Laboratory of Heart Center, Translational Medicine Research Center, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China (H.Y., Wenjie Guo, Wenjing Guo, B.C., Z.L., X.C., J.Y., Z.Z., S.A., C.L.).

|September 16, 2025

概括

对于血管光滑肌细胞 (VSMC) 功能至关重要的TAX1BP3蛋白,SUMOylated 调节其核定位. 这种蛋白质通过与YAP-TEAD的相互作用来抑制VSMC的增殖,从而防止新极度增生.

科学领域:

血管生物学
分子细胞生物学
生物化学

背景情况:

尽管目前的策略存在挑战,但新阴性增生是动脉干预后血管并发症的主要原因.
在生物过程中,PDZ域介导的蛋白-蛋白相互作用至关重要,但它们在新密的形成中的作用在很大程度上尚未被探索.
TAX1BP3是一种独特的PDZ蛋白质,正在研究其在血管光滑肌细胞 (VSMC) 类型转换和新极限增生症中的作用.

研究的目的:

调查TAX1BP3在VSMC表型切换中的作用.
为了阐明TAX1BP3在新极端增生症中的影响.
了解TAX1BP3在血管疾病中的作用的分子机制.

主要方法:

在VSMC和小鼠动脉中评估TAX1BP3的亚细胞定位.
构建TAX1BP3突变体以研究SUMOylation对核细胞质转移的影响.
产生特定于VSMC的Tax1bp3淘汰小鼠,并使用动脉电线损伤模型.
结合RNA测序和ATAC-seq,计算结构预测和共免疫沉.
使用AAV介导基因传递和纳米封装TAX1BP3的体内研究.

主要成果:

在VSMC表型切换过程中,TAX1BP3表现出动态核细胞质转移,由K116的SUMOylation调节.
TAX1BP3缺乏促进VSMC转变为合成表型,并加剧新极限增生症.
TAX1BP3通过YAP-TEAD转录活动调节VSMC细胞周期和增殖,以非正规的PDZ方式与YAP结合竞争.
基因输送和TAX1BP3的纳米封装显著降低了新极端增生和动脉样硬化进展.

结论:

在K116中TAX1BP3的SUMOylation对于其在VSMC表型切换中的核细胞体转移和保护作用至关重要.
TAX1BP3与YAP-TEAD具有竞争性相互作用,抑制VSMC的增殖并减轻新极性增生症.
TAX1BP3 代表了预防神经增生和动脉样等血管并发症的潜在治疗点.

关键词:

PDZ域名动脉疾病细胞增殖血管损伤血管平滑肌肉

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