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通过DDI2对血管素的蛋白质活性激活促进了血管生成

Yu Wang¹, Yuwen Zhu¹, Yebin Wang¹

¹Institute of Pediatrics, Children's Hospital of Fudan University, and the Shanghai Key Laboratory of Medical Epigenetics, the International Co-laboratory of Medical Epigenetics and Metabolism, the State Key Laboratory of Genetic Engineering, Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai, China.

The EMBO journal

|June 23, 2023

概括

由DDI2和其他因素调节的血管蛋白 (AMOT) 裂变对于胚胎血管生成至关重要. 它的C端产物 (AMOT-CT) 驱动血管扩张,而不可食用的AMOT则抑制了它.

科学领域:

分子生物学分子生物学
发展生物学发展生物学
生物化学生物化学

背景情况:

血管蛋白 (AMOT) 是脊椎动物胚胎血管生成的关键支架蛋白.
Lysophosphatidic 酸 (LPA) 是一种涉及血管生成的脂质生长因子.

研究的目的:

研究AMOT裂变的机制及其在血管生成中的作用.
确定调节AMOT裂变的信号通路及其功能后果.

主要方法:

研究了由酸酸 (LPA) 诱导的AMOT裂变.
鉴定了DNA损伤诱导性1同位素2 (DDI2) 作为调解AMOT裂变的阿斯巴拉特蛋白酶.
检查了神经纤维素2 (NF2),坦基酶1/2 (TNKS1/2) 和RING指蛋白146 (RNF146) 在AMOT局部化,多ADP核糖化和无处不在化中的调节作用.
利用斑马鱼和小鼠模型研究AMOT裂变调节对血管生成的体内影响.
评估了AMOT裂变产品,特别是AMOT-CT在血管发育中的功能.

主要成果:

在LPA的存在下,AMOT经历了裂变,通过DDI2.2进行介导.
NF2,TNKS1/2和RNF146形成一个信号轴,调节AMOT裂变.
斑马鱼和小鼠中AMOT裂变调节者的遗传失活导致了缺陷的血管生成.
过度表达AMOT-CT可以挽救血管新生缺陷.
在生理和病理血管生成中,AMOT-CT对于血管扩张至关重要.
发现不可食用的AMOT可以抑制血管生成.

结论:

一个新的信号通路通过分离依赖AMOT的激活来调节血管生成.
由NF2,TNKS1/2和RNF146调节的DDI2的AMOT裂变是控制血管生成的关键步骤.
AMOT C-终端产物 (AMOT-CT) 是血管扩张的关键媒介,突出了调节血管形成的新机制.

关键词:

艾莫特 (AMOT) 是一个名为阿莫特的小镇.DDI2DI2 DDI2DI2 DDI2 DDI2 DDI2 DDI2 DDI2 DDI2 DDI2 DDI2 NF2 NF2 是一个字母.血管新生是因为血管新生.蛋白质酶蛋白质酶是一种蛋白质.

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