RASSF4/AD037 is a potential ras effector/tumor suppressor of the RASSF family
RASSF4/AD037 is a potential ras effector/tumor suppressor of the RASSF family
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DOI：
10.1158/0008-5472.can-04-2065
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发表时间：
2004-12-01
期刊：
影响因子：
11.2
通讯作者：
Clark, GI
中科院分区：
文献类型：
--
作者：
Eckfeld, K;Hesson, L;Clark, GI
激活的RAS蛋白与广泛的效应蛋白相互作用，引起一系列不同的生物学后果。尽管激活的RAS通常与促进生长和转化有关，但它也可能诱导生长拮抗作用，如衰老或凋亡。现在很明显，RAS的一些生长抑制特性是通过RAS效应/肿瘤抑制因子RASSF家族介导的。到目前为止，已经确定了该家族的四个成员(Nore1、RASSF1、RASSF2和RASSF3)。我们现在确定这个组的第五个成员，RASSF4(AD037)。RASSF4与RASSF1的同源性约为25%，与RASSF2的同源性约为60%。RASSF4通过效应域以依赖于GTP的方式直接与激活的K-RAS结合，从而表现出RAS效应器的基本特性。RASSF4过表达可诱导293-T细胞RAS依赖性凋亡，抑制肿瘤细胞生长。虽然RASSF4在正常组织中广泛表达，但在人类肿瘤细胞中经常受到启动子甲基化的下调。因此，RASSF4似乎是RASSF家族中潜在的RAS效应/肿瘤抑制因子的新成员。
Activated Ras proteins interact with a broad range of effector proteins to induce a diverse series of biological consequences. Although typically associated with enhanced growth and transformation, activated Ras may also induce growth antagonistic effects such as senescence or apoptosis. It is now apparent that some of the growth-inhibitory properties of Ras are mediated via the RASSF family of Ras effector/tumor suppressors. To date, four members of this family have been identified (Nore1, RASSF1, RASSF2, and RASSF3). We now identify a fifth member of this group, RASSF4 (AD037). RASSF4 shows approximately 25% identity with RASSF1A and 60% identity with RASSF2. RASSF4 binds directly to activated K-Ras in a GTP-dependent manner via the effector domain, thus exhibiting the basic properties of a Ras effector. Overexpression of RASSF4 induces Ras-dependent apoptosis in 293-T cells and inhibits the growth of human tumor cell lines. Although broadly expressed in normal tissue, RASSF4 is frequently down-regulated by promoter methylation in human tumor cells. Thus, RASSF4 appears to be a new member of the RASSF family of potential Ras effector/tumor suppressors.