Richter Antje M, Pfeifer Gerd P, Dammann Reinhard H
Institute for Genetics, Justus Liebig University Giessen, Heinrich-Buff-Ring 58-62, D-35392 Giessen, Germany.
Biochim Biophys Acta. 2009 Dec;1796(2):114-28. doi: 10.1016/j.bbcan.2009.03.004. Epub 2009 Mar 31.
The Ras-Association Domain Family (RASSF) comprises ten members, termed RASSF1 to RASSF10. RASSF1 to RASSF6 harbor a C-terminal Ras-association (RA) domain and RASSF7 to RASSF10 contain an N-terminal RA domain. Interestingly, it was observed that in various tumor types distinct RASSFs transcripts (e.g. RASSF1A and RASSF2A) are missing due to hypermethylation of their CpG island promoter. Since methylation of the RASSF1A promoter is described as an early and frequent event in tumorigenesis, RASSF1A could serve as a useful diagnostic marker in cancer screens. RASSFs are implicated in various cellular mechanisms including apoptosis, cell cycle control and microtubule stabilization, though little is known about the underlying mechanisms. Tumor suppressing functions were reported for several members. Here we review the current literature on RASSF members focusing on structural, functional and epigenetic aspects. Characterizing the cellular mechanisms that regulate the signaling pathways RASSFs are involved in, could lead to a deeper understanding of tumor development and, furthermore, to new strategies in cancer treatment.
Ras 关联结构域家族（RASSF）由十个成员组成，分别称为 RASSF1 至 RASSF10。RASSF1 至 RASSF6 含有一个 C 末端 Ras 关联（RA）结构域，而 RASSF7 至 RASSF10 包含一个 N 末端 RA 结构域。有趣的是，据观察，在各种肿瘤类型中，由于其 CpG 岛启动子的高甲基化，不同的 RASSF 转录本（如 RASSF1A 和 RASSF2A）缺失。由于 RASSF1A 启动子的甲基化被描述为肿瘤发生过程中的早期频繁事件，RASSF1A 可作为癌症筛查中有用的诊断标志物。RASSF 参与多种细胞机制，包括细胞凋亡、细胞周期控制和微管稳定，尽管对其潜在机制知之甚少。已有报道称几个成员具有肿瘤抑制功能。在此，我们综述了关于 RASSF 成员的当前文献，重点关注结构、功能和表观遗传学方面。阐明调节 RASSF 所参与信号通路的细胞机制，可能会加深对肿瘤发展的理解，并进而为癌症治疗带来新策略。
