The role of Ras-related proteins in transformation

Ras癌基因是一个相关蛋白大家族的一部分。许多这些ras相关蛋白被怀疑在致瘤转化中起作用。事实上，某些Ras相关蛋白似乎是Ras信号传导和转化的下游组分。我们关注的是那些不仅与Ras具有结构同源性，而且与Ras经历相同类型脂质加工的蛋白，即法尼化。抑制法尼基化的药物（法尼基转移酶抑制剂或FTIs）对Ras功能至关重要，目前正在美国国立卫生研究院进行临床试验。因此，了解其他法酰化蛋白在生长发育中的总体重要性可能具有相当大的临床意义。我们发现新的Ras相关蛋白Rho6和Rho7也被法酰化，并且似乎作为Ras转化某些方面的抑制剂。此外，这种抑制作用依赖于Rho6/7法尼化。研究正在进行，以确定这些蛋白质是否可能作为肿瘤抑制因子发挥作用。如果是这样，长期使用fti可能会无意中使肿瘤抑制因子失活。我们还研究了一种新的Ras相关蛋白，我们将其命名为ARHI2。该蛋白与Ras和肿瘤抑制蛋白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 focused 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 essential 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.