Department of Medical Biochemistry, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan.
Department of Biochemistry and Molecular Biology, University of Rajshahi, Rajshahi, 6205, Bangladesh.
Cell Mol Life Sci. 2018 May;75(10):1773-1787. doi: 10.1007/s00018-018-2756-5. Epub 2018 Jan 20.
Human genome has ten genes that are collectedly called Ras association domain family (RASSF). RASSF is composed of two subclasses, C-RASSF and N-RASSF. Both N-RASSF and C-RASSF encode Ras association domain-containing proteins and are frequently suppressed by DNA hypermethylation in human cancers. However, C-RASSF and N-RASSF are quite different. Six C-RASSF proteins (RASSF1-6) are characterized by a C-terminal coiled-coil motif named Salvador/RASSF/Hippo domain, while four N-RASSF proteins (RASSF7-10) lack it. C-RASSF proteins interact with mammalian Ste20-like kinases-the core kinases of the tumor suppressor Hippo pathway-and cross-talk with this pathway. Some of them share the same interacting molecules such as MDM2 and exert the tumor suppressor role in similar manners. Nevertheless, each C-RASSF protein has distinct characters. In this review, we summarize our current knowledge of how C-RASSF proteins play tumor suppressor roles and discuss the similarities and differences among C-RASSF proteins.
人类基因组中有十个基因被统称为 Ras 相关结构域家族 (RASSF)。RASSF 由两个亚类组成，C-RASSF 和 N-RASSF。N-RASSF 和 C-RASSF 均编码 Ras 相关结构域蛋白，并且在人类癌症中经常被 DNA 超甲基化抑制。然而，C-RASSF 和 N-RASSF 有很大的不同。六个 C-RASSF 蛋白（RASSF1-6）的特征是 C 末端卷曲螺旋基序，命名为 Salvador/RASSF/Hippo 结构域，而四个 N-RASSF 蛋白（RASSF7-10）缺乏它。C-RASSF 蛋白与哺乳动物 Ste20 样激酶相互作用——肿瘤抑制因子 Hippo 通路的核心激酶，并与该通路相互作用。其中一些具有相同的相互作用分子，如 MDM2，并以类似的方式发挥肿瘤抑制作用。然而，每个 C-RASSF 蛋白都有其独特的特征。在这篇综述中，我们总结了目前关于 C-RASSF 蛋白如何发挥肿瘤抑制作用的知识，并讨论了 C-RASSF 蛋白之间的相似性和差异性。
