Brioschi Maura, Martinez Fernandez Alma, Banfi Cristina
a Centro Cardiologico Monzino , IRCCS , Milano , Italy.
Expert Rev Proteomics. 2017 Jun;14(6):515-528. doi: 10.1080/14789450.2017.1332998. Epub 2017 May 26.
Protein prenylation is a ubiquitous covalent post-translational modification characterized by the addition of farnesyl or geranylgeranyl isoprenoid groups to a cysteine residue located near the carboxyl terminal of a protein. It is essential for the proper localization and cellular activity of numerous proteins, including Ras family GTPases and G-proteins. In addition to its roles in cellular physiology, the prenylation process has important implications in human diseases and in the recent years, it has become attractive target of inhibitors with therapeutic potential. Areas covered: This review attempts to summarize the basic aspects of prenylation integrating them with biological functions in diseases and giving an account of the current status of prenylation inhibitors as potential therapeutics. We also summarize the methodologies for the characterization of this modification. Expert commentary: The growing body of evidence suggesting an important role of prenylation in diseases and the subsequent development of inhibitors of the enzymes responsible for this modification lead to the urgent need to identify the full spectrum of prenylated proteins that are altered in the disease or affected by drugs. Proteomic tools to analyze prenylated proteins are recently emerging, thanks to the advancement in the field of mass spectrometry coupled to enrichment strategies.
蛋白质异戊二烯化是一种普遍存在的共价翻译后修饰，其特征是将法尼基或香叶基香叶基类异戊二烯基团添加到蛋白质羧基末端附近的半胱氨酸残基上。它对于众多蛋白质的正确定位和细胞活性至关重要，包括Ras家族GTP酶和G蛋白。除了在细胞生理学中的作用外，异戊二烯化过程在人类疾病中也具有重要意义，近年来，它已成为具有治疗潜力的抑制剂的有吸引力靶点。涵盖领域：本综述试图总结异戊二烯化的基本方面，将其与疾病中的生物学功能相结合，并介绍异戊二烯化抑制剂作为潜在治疗药物的现状。我们还总结了表征这种修饰的方法。专家评论：越来越多的证据表明异戊二烯化在疾病中起重要作用，以及随后负责这种修饰的酶抑制剂的开发，导致迫切需要确定在疾病中发生改变或受药物影响的所有异戊二烯化蛋白质。由于质谱领域与富集策略相结合的进展，用于分析异戊二烯化蛋白质的蛋白质组学工具最近正在兴起。
