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。这些Ras相关蛋白中的许多被怀疑在致瘤转化中发挥作用。事实上，某些Ras相关蛋白似乎充当Ras信号传导和转化的下游组分。 我们已经集中在这些蛋白质，不仅共享结构同源性的Ras，但也经历了相同类型的脂质加工作为Ras，法尼基化。针对抑制法尼基化的药物（法尼基转移酶抑制剂或FTIs），这是Ras功能所必需的，目前正在NIH进行临床试验。因此，了解其他法尼基化蛋白在生长和发育中的整体重要性可能具有相当大的临床意义。 我们已经发现，新的Ras相关蛋白质Rho 6和Rho 7也是法尼基化的，并且似乎作为Ras转化的某些方面的抑制剂。此外，抑制作用依赖于Rho 6/7法尼基化。研究正在进行中，以确定这些蛋白质是否可以作为肿瘤抑制剂发挥作用。如果是这样的话，长期使用FTIs可能有助于抑制肿瘤抑制剂。 我们还研究了一种新的Ras相关蛋白，通过数据库搜索确定，我们已指定为ARHI2。该蛋白与Ras和肿瘤抑制因子Noey1/Arhi具有同源性。

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.