In eukaryotes, the synthesis and uptake of sterols undergo stringent multivalent regulation. Both individual enzymes and transcriptional networks are controlled to meet changing needs of the many sterol pathway products. Regulation is tailored by evolution to match regulatory constraints, which can be very different in distinct species. Nevertheless, a broadly conserved feature of many aspects of sterol regulation is employment of proteostasis mechanisms to bring about control of individual proteins. Proteostasis is the set of processes that maintain homeostasis of a dynamic proteome. Proteostasis includes protein quality control pathways for the detection, and then the correction or destruction, of the many misfolded proteins that arise as an unavoidable feature of protein-based life. Protein quality control displays not only the remarkable breadth needed to manage the wide variety of client molecules, but also extreme specificity toward the misfolded variants of a given protein. These features are amenable to evolutionary usurpation as a means to regulate proteins, and this approach has been used in sterol regulation. We describe both well-trod and less familiar versions of the interface between proteostasis and sterol regulation and suggest some underlying ideas with broad biological and clinical applicability.

中文翻译：

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甾醇调节策略中的蛋白质静力学策略

在真核生物中，固醇的合成和摄取经历严格的多价调节。单个酶和转录网络都受到控制，可以满足许多固醇途径产品不断变化的需求。调节是通过进化来定制的，以匹配调节约束，在不同物种中调节约束可能有很大不同。然而，固醇调节的许多方面的广泛保守的特征是采用了蛋白质稳定机制来实现对单个蛋白质的控制。蛋白质稳定是维持动态蛋白质组动态平衡的一组过程。蛋白质变形包括蛋白质质量控​​制途径，用于检测许多错误折叠的蛋白质，然后进行校正或破坏，这些错误折叠的蛋白质是基于蛋白质的生命不可避免的特征。蛋白质质量控​​制不仅显示出管理各种客户分子所需的显着广度，而且还显示出对给定蛋白质错误折叠的变体的极端特异性。这些特征适合作为控制蛋白质的进化途径，这种方法已用于固醇调节。我们描述了蛋白稳定和固醇调节之间的接口的传统和不太熟悉的版本，并提出了一些具有广泛生物学和临床适用性的基本思想。