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Searching new targets for anticancer drug design: The families of Ras and Rho GTPases and their effectors

机译:寻找抗癌药物设计的新目标:Ras和Rho GTPases家族及其效应子

摘要

The Ras superfamily of low-molecular-weight GTPases are proteins that, in response to diverse stimuli, control key cellular processes such as cell growth and development, apoptosis, lipid metabolism, cytoarchitecture, membrane trafficking, and transcriptional regulation. More than 100 genes of this superfamily grouped in six subfamilies have been described so far, pointing to the complexities and specificities of their cellular functions. Dysregulation of members of at least two of these families (the Ras and the Rho families) is involved in the events that lead to the uncontrolled proliferation and invasiveness of human tumors. In recent years, the cloning and characterization of downstream effectors for Ras and Rho proteins have given crucial clues to the specific pathways that lead to aberrant cellular growth and ultimately to tumorigenesis. A direct link between the functions of some of these effectors with the appearance of transformed cells and their ability to proliferate and invade surrounding tissues has been made. Accordingly, drugs that specifically alter their functions display antineoplasic properties, and some of these drugs are already under clinical trials. In this review, we survey the progress made in understanding the underlying molecular connections between carcinogenesis and the specific cellular functions elicited by some of these effectors. We also discuss new drugs with antineoplastic or antimetastatic activity that are targeted to specific effectors for Ras or Rho proteins. © 2001.
机译:低分子量GTP酶的Ras超家族是响应各种刺激而控制关键细胞过程(例如细胞生长和发育,细胞凋亡,脂质代谢,细胞结构,膜运输和转录调节)的蛋白质。迄今为止,已经描述了该超家族的100个基因,这些超家族被分为六个亚家族,指出了其细胞功能的复杂性和特异性。这些家族中至少两个家族(Ras和Rho家族)成员的失调与导致人类肿瘤不受控制的增殖和侵袭的事件有关。近年来,Ras和Rho蛋白下游效应子的克隆和表征为导致异常细胞生长并最终导致肿瘤发生的特定途径提供了关键线索。这些效应器中某些效应器的功能与转化细胞的外观及其增殖和侵袭周围组织的能力之间已经建立了直接联系。因此,特异性改变其功能的药物显示出抗肿瘤特性,并且其中一些药物已经在临床试验中。在这篇综述中,我们调查了了解致癌作用与某些效应物引起的特定细胞功能之间潜在的分子联系的进展。我们还将讨论具有抗肿瘤或抗转移活性的新药物,这些药物针对Ras或Rho蛋白的特定效应子。 ©2001。

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