USP37稳定SREBP1a促进胆固醇摄取和脂质沉积

USP37 Promotes Cholesterol Uptake and Lipid Deposition by Stabilizing SREBP1a

目的筛选影响胆固醇调节元件结合蛋白1a(cholesterol regulatory element binding protein,SREBP1a)蛋白稳定性的去泛素化酶,并探索其调控机制。方法通过去泛素化酶库筛选显著影响SREBP1a表达的去泛素化酶,免疫蛋白印记实验和实时荧光定量PCR(qRT-PCR)评估去泛素化酶对SREBP1a以及升脂基因表达的影响;通过红色荧光蛋白标记人源低密度脂蛋白(human Dil-low density lipoprotein,Human Dil-LDL)摄取和油红O染色等实验技术检测细胞摄取低密度脂蛋白(LDL)和脂质沉积情况。结果去泛素化酶库筛选发现泛素特异肽酶37(ubiquitin specific peptidase 37,USP37)可显著增加肝细胞SREBP1a蛋白表达水平,促进胆固醇摄取及脂质沉积。USP37基因敲除可显著降低SREBP1a蛋白表达水平,抑制升脂基因表达及脂质沉积。结论去泛素化酶USP37通过稳定SREBP1a蛋白表达,促进胆固醇摄取及脂质沉积,揭示了SREBP1a翻译后调控的新模式。

Objective To explore the role of deubiquitination enzymes in the post-translational regulation of cholesterol regulatory element binding protein 1a(SREBP1a)and the corresponding mechanisms.Methods The effects of deubiquitination enzyme on the expression of SREBP1a and lipid-raising gene were investigated by immunoprotein imprinting and real-time fluorescent quantitative PCR(qRT-PCR).The ubiquitization level of SREBP1a was evaluated by immunoprecipitation.LDL uptake and lipid deposition were detected by human Dil-low density lipoprotein(Dil-LDL)uptake and oil red O staining.Results SREBP1a promoted cholesterol uptake and lipid deposition.Ubiquitin specific peptidase 37(USP37)could increase the protein expression level of SREBP1a and promote cholesterol uptake and lipid deposition.USP37 gene knockout could inhibit the expression of lipid-raising gene and lipid deposition.Conclusion Deubiquitination enzyme USP37 promotes cholesterol uptake and cellular lipid deposition by stabilizing SREBP1a protein expression,revealing the post-translational regulation mode of SREBP1a gene expression.