Der C J, Cox A D
La Jolla Cancer Research Foundation, California 92037.
Cancer Cells. 1991 Sep;3(9):331-40.
Association of ras protein with the plasma membrane is critical for its transforming activity. This association is promoted by a series of post-translational modifications that are signaled by the consensus C-terminal CAAX motif present in all ras proteins. The recent discovery that a 15-carbon isoprenoid (farnesyl) group, derived from an essential intermediate in cholesterol biosynthesis, is attached covalently to ras proteins has stimulated considerable interest and has suggested several important new directions for ras studies. In particular, one promising pharmacologic approach for antagonizing oncogenic ras activity in human malignancies would be to design specific inhibitors of the enzymes that catalyze ras processing and thereby interfere with ras protein association with the plasma membrane.
Ras蛋白与质膜的结合对其转化活性至关重要。这种结合由一系列翻译后修饰所促进，这些修饰由所有Ras蛋白中存在的共有C末端CAAX基序发出信号。最近发现，一种源自胆固醇生物合成必需中间体的15碳异戊二烯（法尼基）基团共价连接到Ras蛋白上，这引起了人们极大的兴趣，并为Ras研究提出了几个重要的新方向。特别是，一种在人类恶性肿瘤中拮抗致癌Ras活性的有前景的药理学方法是设计催化Ras加工的酶的特异性抑制剂，从而干扰Ras蛋白与质膜的结合。
