The Role of Nore1 Class Effectors in Ras-Mediated Transf

RAS癌基因介导了促进肿瘤转化的多种生物学效应。然而，激活形式的RAS也有许多令人惊讶的抗转化方面。它们可以诱导衰老、细胞周期停滞，甚至通过细胞凋亡而死亡。这些抗肿瘤作用背后的机制仍然知之甚少。我们已经确定了一类新的RAS效应器，它们似乎介导了RAS的一些抗肿瘤活性。尤其是细胞凋亡。我们现在已经确定，这个家族中至少有三个成员展示了RAS效应器的所有经典特征，同时也展示了肿瘤抑制因子的特性。也就是说，它们介导了对细胞生长和转化的抑制，并在肿瘤发展过程中经常受到表观遗传机制的下调。我们现在有初步数据表明，这个家族的另外两个成员也有类似的特性。因此，我们已经鉴定并部分鉴定了一类新的RAS激活的肿瘤抑制因子。我们目前正在研究这些蛋白质的作用机制。

The Ras oncogene mediates a variety of biological effects that promote tumorigenic transformation. However, activated forms of Ras also have a surprising number anti-transformation aspects. They can induce senesence, cell cycle arrest, and even death by apoptosis. The mechanisms behind these anti-neoplastic effects remain poorly understood. We have identified a family of novel Ras effectors which appear to mediate some of the anti-neoplastic activities of Ras. especially apoptosis. We have now determined that at least three members of this family exhibit all the classic hallmarks of Ras effectors yet also demonstrate the properties of tumor suppressors. Namely, they mediate inhibition of cell growth and transformation and are frequently down-regulated by epigenetic mechanisms during tumor development. We now have preliminary data that two other members of this family have similar properties. Thus, we have identified and partially characterized a novel class of Ras-activated tumor suppressor. We are currently investigating the mechanism of action of these proteins.