Feedback regulation of cholesterol uptake by the LXR-IDOL-LDLR axis.
Feedback regulation of cholesterol uptake by the LXR-IDOL-LDLR axis.
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DOI：
10.1161/atvbaha.112.250571
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发表时间：
2012-11
期刊：
影响因子：
--
通讯作者：
Tontonoz P
中科院分区：
文献类型：
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作者：
Zhang L;Reue K;Fong LG;Young SG;Tontonoz P
低密度脂蛋白受体诱导降解酶（IDOL）是一种E3泛素连接酶，介导低密度脂蛋白受体（LDLR）的泛素化和降解。IDOL的表达在转录水平由胆固醇敏感核受体LXR控制。作为对升高的细胞固醇水平的响应，活化的LXR诱导IDOL产生，从而限制通过LDLR途径进一步摄取外源性胆固醇。胆固醇摄取反馈抑制的LXR-IDOL-LDLR机制独立于SREBP途径，并与之互补。自从LXR-IDOL通路的最初描述以来，生化研究已经帮助定义了IDOL靶标识别和LDLR泛素转移的结构基础。最近的工作也表明IDOL和人类脂质代谢之间的联系。
Inducible Degrader Of the Low-density lipoprotein receptor (IDOL) is an E3 ubiquitin ligase that mediates the ubiquitination and degradation of the low-density lipoprotein receptor (LDLR). IDOL expression is controlled at the transcriptional level by the cholesterol-sensing nuclear receptor LXR. In response to rising cellular sterol levels, activated LXR induces IDOL production, thereby limiting further uptake of exogenous cholesterol through the LDLR pathway. The LXR–IDOL–LDLR mechanism for feedback inhibition of cholesterol uptake is independent of and complementary to the SREBP pathway. Since the initial description of the LXR–IDOL pathway, biochemical studies have helped to define the structural basis for both IDOL target recognition and LDLR ubiquitin transfer. Recent work has also suggested links between IDOL and human lipid metabolism.