蛋白质脂化在细胞信号转导和疾病中的作用、调控及治疗机遇。
Protein Lipidation in Cell Signaling and Diseases: Function, Regulation, and Therapeutic Opportunities.
机构信息
Cutaneous Biology Research Center, Massachusetts General Hospital, Harvard Medical School, 149, 13th St., Charlestown, MA 02129, USA.
Cutaneous Biology Research Center, Massachusetts General Hospital, Harvard Medical School, 149, 13th St., Charlestown, MA 02129, USA.
出版信息
Cell Chem Biol. 2018 Jul 19;25(7):817-831. doi: 10.1016/j.chembiol.2018.05.003. Epub 2018 May 31.
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.
蛋白质脂化是一种重要的翻译后修饰，其中脂质部分与蛋白质共价结合。脂化显著增加了蛋白质的疏水性，导致其构象、稳定性、膜结合、定位、运输以及与辅助因子的结合亲和力发生变化。各种脂质和脂质代谢物作为蛋白质脂化的基团。这些脂质及其衍生物的细胞内浓度受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，蛋白质脂化的失调与各种疾病有关，包括神经紊乱、代谢疾病和癌症。在这篇综述中，我们强调了近年来对蛋白质脂化（特别是 S-棕榈酰化和赖氨酸脂肪酸酰化）的理解方面的最新进展，并描述了这些修饰对蛋白质调控、细胞信号传递和疾病的重要性。我们还强调了针对蛋白质脂化的治疗应用的机会和新策略。
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