RASSF6 is a novel member of the RASSF family of tumor suppressors
RASSF6 is a novel member of the RASSF family of tumor suppressors
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DOI：
10.1038/sj.onc.1210440
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发表时间：
2007-09-13
期刊：
影响因子：
8
通讯作者：
Clark, G. J.
中科院分区：
文献类型：
--
作者：
Allen, N. P. C.;Donninger, H.;Clark, G. J.
RASSF 家族蛋白是肿瘤抑制因子，在人类癌症的发展过程中经常被下调。该家族中最具特征的成员是 RASSF1A，它在 40-90% 的原发性人类肿瘤中通过启动子甲基化下调。我们现在鉴定并表征了 RASSF 家族的新成员 RASSF6。与其他家族成员一样，RASSF6 拥有 Ras 关联结构域并结合激活的 Ras。 RASSF6的外源表达促进细胞凋亡，与活化的K-Ras协同诱导细胞死亡并抑制特定肿瘤细胞系的存活。 RASSF6 的抑制增强了人肺肿瘤细胞系的致瘤表型。此外，RASSF6 在人类原发性肿瘤中经常下调。 RASSF6 与其他 RASSF 蛋白具有一些相似的总体特性。然而，RASSF6 和其他家族成员（包括离散组织表达亲）之间的生物活性存在显着差异。 le，细胞杀伤特异性和对信号通路的影响。此外，RASSF6可能在决定呼吸道合胞病毒的炎症反应程度方面发挥作用。因此，RASSF6是一个新的RASSF家族成员，它表现出Ras效应子和肿瘤抑制子的特性，但表现出独特且不同于其他家族成员的生物学特性。
RASSF family proteins are tumor suppressors that are frequently downregulated during the development of human cancer. The best-characterizedmember of the family is RASSF1A, which is downregulated by promoter methylation in 40-90% of primary human tumors. We now identify and characterize a novel member of the RASSF family, RASSF6. Like the other family members, RASSF6 possesses a Ras Association domain and binds activated Ras. Exogenous expression of RASSF6 promotedapoptosis, synergized with activated K-Ras to induce cell death and inhibited the survival of specific tumor cell lines. Suppression of RASSF6 enhanced the tumorigenic phenotype of a human lung tumor cell line. Furthermore, RASSF6 is often downregulated in primary human tumors. RASSF6 shares some similar overall properties as other RASSF proteins. However, there are significant differences in biological activity between RASSF6 and other family members including a discrete tissue expression pro. le, cell killing specificity and impact on signaling pathways. Moreover, RASSF6 may play a role in dictating the degree of in. ammatory response to the respiratory syncytial virus. Thus, RASSF6 is a novel RASSF family member that demonstrates the properties of a Ras effector and tumor suppressor but exhibits biological properties that are unique and distinct from those of other family members.