THE ROLE OF RAS-RELATED PROTEINS IN TRANSFORMATION

RAS癌基因是相关蛋白质大家族的一部分。 其中许多与RAS相关的蛋白被怀疑发挥着 在致瘤转化中的作用。事实上，某些RAS 相关的蛋白质似乎是下游的组成部分 RAS信号和转化。我们关注的重点是 不仅与RAS有结构同源性的蛋白质，而且 也经历与RAS相同类型的脂质处理， 法尼化。针对抑制法尼化的药物 (法尼基转移酶抑制剂或FTI)，这是必不可少的 对于RAS功能，目前正在NIH进行临床试验。 因此，理解其他因素的整体重要性 法尼化蛋白在生长和发育中可能有 有相当大的临床相关性。我们发现这部小说 RAS相关蛋白Rho6和Rho7也是法尼化的 似乎对RAS的某些方面起抑制作用 转型。此外，抑制作用依赖于 Rho6/7法尼化。目前正在进行研究，以确定 这些蛋白质可能作为肿瘤抑制因子发挥作用。如果是的话， 长期使用FTI可能会在不经意间 使肿瘤抑制因子失活。我们还在研究一部小说RAS 通过数据库搜索确定的相关蛋白质 已经指定了ARHI2。这种蛋白质与RAS有同源性 以及肿瘤抑制基因Noey1/ARHI。

Ras oncogenes are part of a large family of related proteins. Many of these Ras-related proteins are suspected of playing a role in tumorigenic transformation. Indeed, certain Ras related proteins appear to serve as downstream components of Ras signaling and transformsation. We have focussed on those proteins which not only share structural homology to Ras, but also undergo the same type of lipid processing as Ras, farnesylation. Drugs directed at inhibiting farnesylation (Farnesyl transferase inhibitors or FTIs), which is essentail for Ras function, are currently in clinical trials at the NIH. Consequently, understanding the overall importance of other farnesylated proteins in growth and development may have considerable clinical relevance. We have found that the novel Ras-related proteins Rho6 and Rho7 are also farnesylated and appear to act as inhibitors of certain aspects of Ras transformation. Moreover, the inhibition is dependent upon Rho6/7 farnesylation. Studies are underway to determine if these proteins may play a role as tumor suppressors. If so, the long term use of FTIs may serve to inadvertantly inactivate tumor suppresors. We are also examining a novel Ras related protein identified by data base searching which we have designated ARHI2. This protein shares homology with Ras and with the tumor suppresor Noey1/Arhi.