Benhar Moran
Department of Biochemistry, Rappaport Institute for Research in the Medical Sciences, Faculty of Medicine, Technion-Israel Institute of Technology, Haifa 31096, Israel.
Curr Med Chem. 2016;23(24):2602-2617. doi: 10.2174/0929867323666160627114839.
Despite long and intensive investigation, the mechanisms by which nitric oxide (NO) regulates immune function and carcinogenesis remain incompletely understood. Protein S-nitrosylation, the covalent attachment of a nitroso group to a cysteine thiol, has emerged as a central mechanism of NO-dependent cellular regulation. In particular, recent research has revealed important roles for S-nitrosylation/denitrosylation in modulating the activity of macrophage and tumor cell proteins, implicating Snitrosylation in the regulation of macrophage function as well as in tumor development and response to therapy. This review summarizes recent progress in the identification and characterization of S-nitrosylated proteins in macrophages and cancer cells. The review highlights key findings and insights obtained from functional and proteomic studies about the roles of S-nitrosylation in signaling, transcription, apoptosis and other cellular processes relevant to macrophage function and cancer progression. Some of the implications of recent discoveries for the development of novel anticancer approaches are also discussed.
尽管进行了长期深入的研究，但一氧化氮（NO）调节免疫功能和致癌作用的机制仍未完全明了。蛋白质S-亚硝基化，即亚硝基基团与半胱氨酸硫醇的共价连接，已成为NO依赖性细胞调节的核心机制。特别是，最近的研究揭示了S-亚硝基化/去亚硝基化在调节巨噬细胞和肿瘤细胞蛋白活性方面的重要作用，这表明S-亚硝基化参与巨噬细胞功能调节以及肿瘤发展和对治疗的反应。本综述总结了巨噬细胞和癌细胞中S-亚硝基化蛋白鉴定和表征的最新进展。该综述强调了从功能和蛋白质组学研究中获得的关于S-亚硝基化在信号传导、转录、细胞凋亡以及与巨噬细胞功能和癌症进展相关的其他细胞过程中作用的关键发现和见解。还讨论了近期发现对新型抗癌方法开发的一些影响。
