RASSF6 is a novel member of the RASSF family of tumor suppressors

被引:101
作者
Allen, N. P. C.
Donninger, H.
Vos, M. D.
Eckfeld, K.
Hesson, L.
Gordon, L.
Birrer, M. J.
Latif, F.
Clark, G. J.
机构
[1] Natl Canc Inst, Dept Cell Canc Biol, Rockville, MD USA
[2] Univ Louisville, JG Brown Canc Ctr, Dept Med, Mol Targets Grp, Louisville, KY USA
[3] Univ Birmingham, Med Sect Mol Genet, Birmingham, W Midlands, England
关键词
Ras; RASSF6; tumor suppressor;
D O I
10.1038/sj.onc.1210440
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:6203 / 6211
页数:9
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