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利用 S-亚硝基化作用进行癌症治疗:事实与展望。

Exploiting S-nitrosylation for cancer therapy: facts and perspectives.

机构信息

Redox Signaling and Oxidative Stress Group, Danish Cancer Society Research Center, 2100 Copenhagen, Denmark.

Center for Healthy Aging, Copenhagen University, Copenhagen, Denmark.

出版信息

Biochem J. 2020 Oct 16;477(19):3649-3672. doi: 10.1042/BCJ20200064.

Abstract

S-nitrosylation, the post-translational modification of cysteines by nitric oxide, has been implicated in several cellular processes and tissue homeostasis. As a result, alterations in the mechanisms controlling the levels of S-nitrosylated proteins have been found in pathological states. In the last few years, a role in cancer has been proposed, supported by the evidence that various oncoproteins undergo gain- or loss-of-function modifications upon S-nitrosylation. Here, we aim at providing insight into the current knowledge about the role of S-nitrosylation in different aspects of cancer biology and report the main anticancer strategies based on: (i) reducing S-nitrosylation-mediated oncogenic effects, (ii) boosting S-nitrosylation to stimulate cell death, (iii) exploiting S-nitrosylation through synthetic lethality.

摘要

S-亚硝基化,即一氧化氮对半胱氨酸的翻译后修饰,已涉及多种细胞过程和组织稳态。因此,在病理状态下,控制 S-亚硝基化蛋白水平的机制发生改变。在过去的几年中,已经提出了 S-亚硝基化在癌症中的作用,这一观点得到了各种癌蛋白在 S-亚硝基化时发生功能获得或功能丧失修饰的证据的支持。在这里,我们旨在深入了解 S-亚硝基化在癌症生物学不同方面的作用的现有知识,并报告主要的基于以下三种策略的抗癌策略:(i)减少 S-亚硝基化介导的致癌作用,(ii)增强 S-亚硝基化以刺激细胞死亡,(iii)通过合成致死作用利用 S-亚硝基化。

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