Chan Jia Jia, Katan Matilda
Institute of Structural and Molecular Biology, Division of Biosciences, University College London, Gower Street, London WC1E 6BT, UK.
Adv Biol Regul. 2013 Sep;53(3):258-79. doi: 10.1016/j.jbior.2013.07.008. Epub 2013 Aug 1.
Not all proteins implicated in direct binding to Ras appear to have a positive role in the generation and progression of tumours; examples include Phospholipase C epsilon (PLCɛ) and some members of the Ras-association domain family (RASSF). The RASSF family comprises of ten members, known as RASSF1 to RASSF10. PLCɛ and RASSF members carry a common Ras-association domain (RA) that can potentially bind Ras oncoproteins and mediate Ras-regulated functions. RASSF1 to RASSF6 also share a common SARAH domain that facilitates protein-protein interactions with other SARAH domain proteins. The majority of the family are frequently downregulated by epigenetic silencing in cancers. They are implicated in various important biological processes including apoptosis, microtubule stabilisation and cell cycle regulation. Recent studies have reinforced the tumour suppressive properties of the RASSF family, with new evidence of emerging pathways and novel functions that suggest a wider role for these proteins. This review will first describe an emerging role of PLCɛ in tumour suppression and then focus on and summarise the new findings on the RASSF family in the last five years to consolidate their well-established functions, and highlight the new regulatory roles of specific RASSF members.
并非所有与Ras直接结合相关的蛋白质在肿瘤的发生和发展中都起积极作用；例如磷脂酶Cε（PLCɛ）和Ras关联结构域家族（RASSF）的一些成员。RASSF家族由十个成员组成，即RASSF1至RASSF10。PLCɛ和RASSF成员携带一个共同的Ras关联结构域（RA），该结构域可能与Ras癌蛋白结合并介导Ras调节的功能。RASSF1至RASSF6还共享一个共同的SARAH结构域，该结构域促进与其他SARAH结构域蛋白的蛋白质-蛋白质相互作用。该家族的大多数成员在癌症中经常因表观遗传沉默而下调。它们参与各种重要的生物学过程，包括细胞凋亡、微管稳定和细胞周期调控。最近的研究强化了RASSF家族的肿瘤抑制特性，有新的证据表明出现了新的途径和新功能，这表明这些蛋白质具有更广泛的作用。本综述将首先描述PLCɛ在肿瘤抑制中的新作用，然后重点总结过去五年中关于RASSF家族的新发现，以巩固其已确立的功能，并突出特定RASSF成员的新调控作用。
