Advances in the regulation of low density lipoprotein receptor by RING-E3 ubiquitin ligase
10.20039/j.cnki.1007-3949.2025.05.010
- VernacularTitle:RING-E3泛素连接酶调控低密度脂蛋白受体的研究进展
- Author:
Fangyuan LIU
1
;
Caiping ZHANG
1
;
Shiyin LONG
1
Author Information
1. 南华大学衡阳医学院生物化学与分子生物学教研室,湖南省衡阳市 421001
- Publication Type:Journal Article
- Keywords:
RING-E3 ubiquitin ligase;
low density lipoprotein receptor;
low density lipoprotein cholesterol;
ubiquitylation;
atherosclerosis
- From:
Chinese Journal of Arteriosclerosis
2025;33(5):440-446
- CountryChina
- Language:Chinese
-
Abstract:
The occurrence and development of atherosclerotic cardiovascular diseases is closely related to abnormally elevated plasma low density lipoprotein cholesterol(LDLC)level.Low density lipoprotein receptor(LDLR)plays a central role in the maintenance of cholesterol homeostasis by mediating the endocytotic clearance of LDLC,and the abundance of LDLR on the surface of the cell membrane is closely related to the expression level and recirculation of LD-LR.Recent studies have found that RING-E3 ubiquitin ligase can regulate LDLR levels through a dual mechanism:on the one hand,it directly ubiquitinates and modifies LDLR to promote its degradation via the endosome-lysosome pathway;on the other hand,it reduces LDLR synthesis through activation of the liver X receptor(LXR)pathway or inhibition of the nuclear translocation of sterol regulatory element-binding protein(SREBP).Together,these two mechanisms lead to a decrease in cell membrane LDLR abundance,impairing cholesterol metabolic homeostasis and exacerbating LDLC accumu-lation.Therefore,targeted inhibition of RING-E3 ubiquitin ligase activity may be a novel strategy to regulate LDLR ex-pression,reduce plasma LDLC levels,and combat cardiovascular disease.This article reviews the mechanism of action of RING-E3 ubiquitin ligase in regulating LDLR and its related research progress.
