Winter-Vann Ann M, Casey Patrick J
Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina 27710, USA.
Nat Rev Cancer. 2005 May;5(5):405-12. doi: 10.1038/nrc1612.
RAS and many other oncogenic proteins undergo a complex series of post-translational modifications that are initiated by the addition of an isoprenoid lipid through a process known as prenylation. Following prenylation, these proteins usually undergo endoproteolytic processing by the RCE1 protease and then carboxyl methylation by a unique methyltransferase known as isoprenylcysteine carboxyl methyltransferase (ICMT). Although inhibitors that have been designed to target the prenylation step are now in advanced-stage clinical trials, their utility and efficacy seem to be limited. Recent findings, however, indicate that the inhibition of these post-prenylation-processing steps--particularly that of ICMT-catalysed methylation--might provide a better approach to the control of cancer-cell proliferation.
RAS和许多其他致癌蛋白会经历一系列复杂的翻译后修饰，这些修饰始于通过一种称为异戊二烯化的过程添加类异戊二烯脂质。异戊二烯化之后，这些蛋白通常会被RCE1蛋白酶进行内切蛋白水解加工，然后由一种名为异戊烯基半胱氨酸羧基甲基转移酶（ICMT）的独特甲基转移酶进行羧基甲基化。尽管设计用于靶向异戊二烯化步骤的抑制剂目前正处于晚期临床试验阶段，但其效用和疗效似乎有限。然而，最近的研究结果表明，抑制这些异戊二烯化后加工步骤——尤其是ICMT催化的甲基化步骤——可能为控制癌细胞增殖提供更好的方法。
