The Ras Superfamily of Small GTPases: The Unlocked Secrets

The Ras Superfamily of Small GTPases: The Unlocked Secrets
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DOI:
10.1007/978-1-62703-791-4_1
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发表时间:
2014-01-01
期刊:
RAS SIGNALING: METHODS AND PROTOCOLS
影响因子:
--
通讯作者:
Retta, Saverio Francesco
Retta, Saverio Francesco
中科院分区:
其他
文献类型:
--
作者:
Goitre, Luca;Trapani, Eliana;Retta, Saverio Francesco

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Ras超家族的小GTP酶由超过150个成员组成,它们具有保守的结构和生化特性,充当通过结合GTP而打开和通过水解GTP为GDP而关闭的二元分子开关。然而,尽管有相当大的结构和生化相似性,这些蛋白质发挥多种和不同的作用,是多才多艺的和关键的监管机构,几乎所有的基本细胞过程。1982年,Ras基因在人类癌细胞系中被突变激活并转化,在此基础上,各种强有力的实验技术被集中用于发现和研究Ras和Ras相关的小GTP酶的结构、生物化学和生物学特性。导致基础研究的突破,大量的Ras超家族成员的识别和结构和功能的表征,以及他们的多个监管机构和effectors.In这篇评论中,我们提供了一个总体概述的主要里程碑,最终允许解开这个大而重要的蛋白质超家族的秘密宝库。
The Ras superfamily of small GTPases is composed of more than 150 members, which share a conserved structure and biochemical properties, acting as binary molecular switches turned on by binding GTP and off by hydrolyzing GTP to GDP. However, despite considerable structural and biochemical similarities, these proteins play multiple and divergent roles, being versatile and key regulators of virtually all fundamental cellular processes. Conversely, their dysfunction plays a crucial role in the pathogenesis of serious human diseases, including cancer and developmental syndromes.Fuelled by the original identification in 1982 of mutationally activated and transforming human Ras genes in human cancer cell lines, a variety of powerful experimental techniques have been intensively focused on discovering and studying structure, biochemistry, and biology of Ras and Ras-related small GTPases, leading to fundamental research breakthroughs into identification and structural and functional characterization of a huge number of Ras superfamily members, as well as of their multiple regulators and effectors.In this review we provide a general overview of the major milestones that eventually allowed to unlock the secret treasure chest of this large and important superfamily of proteins.