Cholesterol is an essential component of mammalian cell membranes and is required for proper membrane permeability, fluidity, organelle identity, and protein function. Cells maintain sterol homeostasis by multiple feedback controls that act through transcriptional and posttranscriptional mechanisms. The membrane-bound transcription factor sterol regulatory element binding protein (SREBP) is the principal regulator of both sterol synthesis and uptake. In mammalian cells, the ER membrane protein Insig has emerged as a key component of homeostatic regulation by controlling both the activity of SREBP and the sterol-dependent degradation of the biosynthetic enzyme HMG-CoA reductase. In this review, we focus on recent advances in our understanding of the molecular mechanisms of the regulation of sterol synthesis. A comparative analysis of SREBP and HMG-CoA reductase regulation in mammals, yeast, and flies points toward an equilibrium model for how lipid signals regulate the activity of sterol-sensing proteins and their downstream effectors.

中文翻译：

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真核生物中固醇合成的调控。

胆固醇是哺乳动物细胞膜的重要组成部分，是适当的膜渗透性，流动性，细胞器特性和蛋白质功能所必需的。细胞通过通过转录和转录后机制起作用的多种反馈控制来维持固醇稳态。膜结合转录因子固醇调节元件结合蛋白（SREBP）是固醇合成和摄取的主要调节剂。在哺乳动物细胞中，通过控制SREBP的活性和生物合成酶HMG-CoA还原酶的固醇依赖性降解，ER膜蛋白Insig已成为稳态调节的关键组成部分。在这篇综述中，我们关注于对固醇合成调节分子机制的最新进展。