Protein prenylation: key to ras function and cancer intervention?
Protein prenylation: key to ras function and cancer intervention?
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发表时间：
1992-07
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通讯作者：
R. Khosravi‐Far;A. Cox;K. Kato;C. Der
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作者：
R. Khosravi‐Far;A. Cox;K. Kato;C. Der
细胞ras蛋白的突变的致癌形式与广谱的人类恶性肿瘤的频繁关联促使了深入的研究，以确定它们在正常细胞生理学中的作用，并确定异常ras功能对人类肿瘤发生的贡献（1-4）。尽管对ras蛋白的结构和生化特性有相当多的了解，但我们对ras蛋白的功能仍然一无所知。最近发现ras转化活性严重依赖于法呢基类异戊二烯（胆固醇生物合成中的必需中间体）的修饰（异戊二烯化），这揭示了ras功能的潜在重要线索，并确定了癌症治疗的新前景（5-8）。在本研究中，我们将总结我们目前对蛋白质异戊烯化在ras生物活性中的作用的理解，并评估药理学方法拮抗异戊烯化的前景和问题。最后，理解蛋白质异戊二烯化在ras功能中的作用将为定义这种以前不清楚的蛋白质修饰对于非常多样化和不断增长的异戊二烯化蛋白质的功能的意义提供基础（9，10）。
Ihe frequent association of mutated, oncogenic forms of cellular ras proteins with a broad spectrum of human malignancies has prompted intensive investigations into identifying their role in normal cellular physiology and into establishing the contribution of aberrant ras function to human tumorigenesis (1-4). Despite considerable knowledge of the structural and biochemical properties of ras proteins, we remain ignorant of the function of ras proteins. The recent discovery that ras transforming activity is critically dependent on modification (prenylation) by a farnesyl isoprenoid, an essential intermediate in cholesterol biosynthesis, has unveiled potentially important clues to ras function and identified novel prospects for cancer therapy (5-8). In this research capsule, we will summarize our present understanding of the role of protein prenylation in ras biological activity, and we will assess the promises and problems of pharmacological approaches to antagonizing prenylation. Finally, understanding the role of protein prenylation in ras function will provide a foundation for defining the significance of this previously obscure protein modification for the functions of a very diverse and growing number of isoprenylated proteins (9, 10).