Regulation of Ras proteins by reactive nitrogen species.
Regulation of Ras proteins by reactive nitrogen species.
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DOI：
10.1016/j.freeradbiomed.2011.05.003
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发表时间：
2011-08-01
影响因子：
7.4
通讯作者：
Campbell, Sharon L.
中科院分区：
文献类型：
--
作者：
Davis, Michael F.;Vigil, Dom;Campbell, Sharon L.
关键词：
自80年代早期以来，Ras GTP酶一直是深入研究的主题，当时Ras中的单点突变显示出引起失调的细胞生长控制。随后，Ras被鉴定为人类癌症中发现的最普遍的癌基因。Ras蛋白通过在非活性GDP结合和活性GTP结合状态之间循环来调节参与细胞生长、分化和凋亡的许多途径。Ras活性的调节由改变鸟嘌呤核苷酸循环的细胞因子控制。致癌突变阻止蛋白质调节因子下调Ras活性，从而维持Ras处于慢性激活状态。该领域的中心法则是蛋白质调节因子是Ras活性的主要调节因子。然而，自90年代中期以来，越来越多的证据表明，小分子活性氮物质（RNS）也可以影响Ras鸟嘌呤核苷酸循环。在此，我们回顾了RNS形成背后的基本化学，并讨论了各种RNS增强Ras蛋白中核苷酸交换的机制。此外，我们目前的研究表明，在免疫系统功能，脑功能和癌症发展的背景下，RNS介导的Ras激活的生理相关性。我们还强调了未来的方向和实验方法，可能会提高我们的能力，在细胞培养和体内检测RNS介导的激活。这些方法的发展可能最终为检测和阐明Ras蛋白如何受到氧化还原物质的调节以及靶向癌症和其他疾病状态中的氧化还原激活的Ras铺平了新的方向。
Ras GTPases have been a subject of intense investigation since the early-80’s, when single point mutations in Ras were shown to cause deregulated cell growth control. Subsequently, Ras was identified as the most prevalent oncogene found in human cancer. Ras proteins regulate a host of pathways involved in cell growth, differentiation, and apoptosis by cycling between inactive GDP-bound and active GTP-bound states. Regulation of Ras activity is controlled by cellular factors that alter guanine nucleotide cycling. Oncogenic mutations prevent protein regulatory factors from down-regulating Ras activity, thereby maintaining Ras in a chronically activated state. The central dogma in the field is that protein modulatory factors are the primary regulators of Ras activity. Since the mid-90’s, however, evidence has accumulated that small molecule reactive nitrogen species (RNS) can also influence Ras guanine nucleotide cycling. Herein, we review the basic chemistry behind RNS formation and discuss the mechanism through which various RNS enhance nucleotide exchange in Ras proteins. In addition, we present studies that demonstrate the physiological relevance of RNS-mediated Ras activation within the context of immune system function, brain function, and cancer development. We also highlight future directions and experimental methods that may enhance our ability to detect RNS-mediated activation in cell cultures and in vivo. The development of such methods may ultimately pave new directions for detecting and elucidating how Ras proteins are regulated by redox species, as well as for targeting redox-activated Ras in cancer and other disease states.
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影响因子：
4.8
作者：
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通讯作者：
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影响因子：
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DOI：
10.1073/pnas.162095599
发表时间：
2002-08-20
影响因子：
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作者：
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通讯作者：
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