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ABCE1可以选择性地促进血管性基因表达的HIF-1α转换活化

Lihui Sun¹, Xueqin Ding², Y James Kang¹

¹Regenerative Medicine Research Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China.

Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS)

|September 22, 2023

概括

铜 (Cu) 结合蛋白ABCE1抑制FIH-1活动,促进血管新生基因的HIF-1转活. 这种机制解释了铜如何影响缺氧诱导因子-1 (HIF-1) 的活性.

科学领域:

分子生物学分子生物学
细胞生物学细胞生物学
生物化学生化学

背景情况:

众所周知,铜 (Cu) 通过抑制抑制因子抑制HIF-1 (FIH-1) 来增强缺氧诱导因子-1 (HIF-1) 转录活性.
铜抑制FIH-1的确切分子机制尚未完全阐明.

研究的目的:

研究铜抑制FIH-1的分子机制.
为了确定与FIH-1相互作用并调解铜作用的蛋白质.

主要方法:

使用的人类静脉内皮细胞 (HUVEC),用DMOG治疗以诱导HIF-1α积累.
进行了蛋白质复合体拉下测试,金属结合部位预测,体外铜结合测试 (Cu-IMAC,ITC) 和亚细胞局部化研究.
使用共免疫沉降 (Co-IP) 验证的蛋白质相互作用,并通过RT-qPCR分析了对HIF-1α转录活性的影响.

主要成果:

确定ATP结合盒E1 (ABCE1) 作为FIH-1复合体内的新型铜结合蛋白.
证明了ABCE1在体外结合铜的能力以及在缺氧下与FIH-1的核转位.
表明ABCE1通过阻止铁结合来抑制FIH-1酶活性,从而导致抑制铜依赖的HIF-1基因的表达.

结论:

在低氧条件下,ABCE1作为一种结合铜的蛋白质,在低氧条件下转移到核中.
ABCE1抑制FIH-1活动,从而防止HIF-1α降解,并促进HIF-1血管新生基因表达的转换活化.

关键词:

在ABCE1中,ABCE1是ABCE1.铜结合蛋白是一种结合铜的蛋白质.在FIH-1中,FIH-1被认为是FIH-1.HIF-1α转录活动.

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