Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, United States; Frederick National Laboratory for Cancer Research, Frederick, MD, United States.
Adv Cancer Res. 2022;153:1-27. doi: 10.1016/bs.acr.2021.07.003. Epub 2021 Sep 14.
In this review, I provide a brief history of the discovery of RAS and the GAPs and GEFs that regulate its activity from a personal perspective. Much of this history has been driven by technological breakthroughs that occurred concurrently, such as molecular cloning, cDNA expression to analyze RAS proteins and their structures, and application of PCR to detect mutations. I discuss the RAS superfamily and RAS proteins as therapeutic targets, including recent advances in developing RAS inhibitors. I also describe the role of the RAS Initiative at Frederick National Laboratory for Cancer Research in advancing development of RAS inhibitors and providing new insights into signaling complexes and interaction of RAS proteins with the plasma membrane.
在这篇综述中，我从个人角度简要回顾了 RAS 的发现历程以及调控其活性的 GAPs 和 GEFs。这一历程在很大程度上受到了同期技术突破的推动，如分子克隆、cDNA 表达以分析 RAS 蛋白及其结构，以及 PCR 技术在检测突变中的应用。我讨论了 RAS 超家族和 RAS 蛋白作为治疗靶点，包括开发 RAS 抑制剂的最新进展。我还描述了弗雷德里克国家癌症研究实验室 RAS 计划在推进 RAS 抑制剂开发方面的作用，以及为信号复合物和 RAS 蛋白与质膜相互作用提供新的见解。
