Rig is a novel Ras-related protein and potential neural tumor suppressor
Rig is a novel Ras-related protein and potential neural tumor suppressor
复制标题
DOI：
10.1073/pnas.142193799
复制
发表时间：
2002-07-23
影响因子：
11.1
通讯作者：
Clark, GJ
中科院分区：
文献类型：
--
作者：
Ellis, CA;Vos, MD;Clark, GJ
RAS超家族由一大组与RAS癌蛋白同源的单体GTP酶组成。虽然结构相似，但RAS超家族蛋白在功能上是不同的。虽然一些成员表现出致癌特性，但其他成员可能是肿瘤抑制因子。我们发现了一种新的抑制细胞生长的RAS相关蛋白，并将其命名为RIG(RAS相关细胞生长抑制因子)。RIG过表达抑制了Ras介导的NIH3T3细胞的细胞转化和下游信号的激活。RIG基因在正常心脏和神经组织中高水平表达。然而，RIG蛋白在神经肿瘤来源的细胞系和原发人类神经肿瘤中的表达经常丢失或下调。此外，外源RIG在人脑星形细胞瘤细胞中的表达抑制了细胞的生长。RIG有一个C-末端CAAX基序，编码法尼基和香叶基异戊二烯基脂的翻译后修饰。因此，RIG可能在细胞对法尼基转移酶抑制剂的反应中发挥作用。RIG与最近描述的RAS家族成员Noey2有63%的序列同源性，Noey2是乳腺和卵巢组织中的一种肿瘤抑制因子。因此，RIG和Noey2可能代表了一个新的RAS样抑癌基因亚家族。
The Ras superfamily consists of a large group of monomeric GTPases demonstrating homology to Ras oncoproteins. Although structurally similar, Ras-superfamily proteins are functionally diverse. Whereas some members exhibit oncogenic properties, others may serve as tumor suppressors. We have identified a novel Ras-related protein that suppresses cell growth and have designated it Rig (Ras-related inhibitor of cell growth). Overexpression of Rig inhibited Ras-mediated cellular transformation and activation of downstream signaling in NIH 3T3 cells. rig mRNA is expressed at high levels in normal cardiac and neural tissue. However, Rig protein expression is frequently lost or down-regulated in neural tumor-derived cell lines and primary human neural tumors. Moreover, expression of exogenous Rig in human astrocytoma cells suppressed growth. Rig has a C-terminal CAAX motif that codes for posttranslational modification by both farnesyl and geranylgeranyl isoprenoid lipids. Consequently, Rig may play a role in the cellular response to farnesyl transferase inhibitors. Rig bears 63% overall sequence homology to a recently described Ras-family member Noey2, a tumor suppressor in breast and ovarian tissue. Therefore, Rig and Noey2 may represent a new subfamily of Ras-like tumor suppressors.