Protein lipidation is an important co- or posttranslational modification in which lipid moieties are covalently attached to proteins. Lipidation markedly increases the hydrophobicity of proteins, resulting in changes to their conformation, stability, membrane association, localization, trafficking, and binding affinity to their co-factors. Various lipids and lipid metabolites serve as protein lipidation moieties. The intracellular concentrations of these lipids and their derivatives are tightly regulated by cellular metabolism. Therefore, protein lipidation links the output of cellular metabolism to the regulation of protein function. Importantly, deregulation of protein lipidation has been linked to various diseases, including neurological disorders, metabolic diseases, and cancers. In this review, we highlight recent progress in our understanding of protein lipidation, in particular, S-palmitoylation and lysine fatty acylation, and we describe the importance of these modifications for protein regulation, cell signaling, and diseases. We further highlight opportunities and new strategies for targeting protein lipidation for therapeutic applications.

中文翻译：

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细胞信号传导和疾病中的蛋白质脂化：功能，调节和治疗的机会。

蛋白质脂化是重要的共翻译或翻译后修饰，其中脂质部分共价附于蛋白质。脂化作用显着增加了蛋白质的疏水性，导致其构象，稳定性，膜缔合，定位，运输和对其辅因子的结合亲和力发生了变化。各种脂质和脂质代谢产物用作蛋白质脂质化部分。这些脂质及其衍生物的细胞内浓度受到细胞代谢的严格调节。因此，蛋白质脂化将细胞代谢的输出与蛋白质功能的调节联系起来。重要的是，蛋白脂质失调与多种疾病有关，包括神经系统疾病，代谢性疾病和癌症。在这篇评论中，我们着重介绍了我们对蛋白质脂化（尤其是S-棕榈酰化和赖氨酸脂肪酰化）的理解的最新进展，并且我们描述了这些修饰对蛋白质调节，细胞信号转导和疾病的重要性。我们进一步强调针对蛋白质脂治疗应用的机会和新策略。