Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA.
Acta Biochim Biophys Sin (Shanghai). 2012 Jan;44(1):70-9. doi: 10.1093/abbs/gmr109.
During the last decade, we saw an explosion of studies investigating the role of lysine methylation/demethylation of histones and non-histone proteins, such as p53, NF-kappaB, and E2F1. These 'Ying-Yang' post-translational modifications are important to fine-tuning the activity of these proteins. Lysine methylation and demethylation are catalyzed by protein lysine methyltransferases (PKMTs) and protein lysine demethylases (PKDMs). PKMTs, PKDMs, and their substrates have been shown to play important roles in cancers. Although the underlying mechanisms of tumorigenesis are still largely unknown, growing evidence is starting to link aberrant regulation of methylation to tumorigenesis. This review focuses on summarizing the recent progress in understanding of the function of protein lysine methylation, and in the discovery of small molecule inhibitors for PKMTs and PKDMs. We also discuss the potential and the caveats of targeting protein lysine methylation for the treatment of cancer.
在过去的十年中，我们见证了大量研究的涌现，这些研究探讨了赖氨酸甲基化/去甲基化在组蛋白和非组蛋白蛋白（如 p53、NF-κB 和 E2F1）中的作用。这些“阴阳”的翻译后修饰对于精细调节这些蛋白质的活性非常重要。赖氨酸甲基化和去甲基化由蛋白质赖氨酸甲基转移酶（PKMTs）和蛋白质赖氨酸去甲基酶（PKDMs）催化。PKMTs、PKDMs 及其底物已被证明在癌症中发挥重要作用。尽管肿瘤发生的潜在机制在很大程度上仍不清楚，但越来越多的证据开始将甲基化的异常调节与肿瘤发生联系起来。这篇综述重点总结了近年来对蛋白质赖氨酸甲基化功能的理解以及对 PKMTs 和 PKDMs 的小分子抑制剂的发现的最新进展。我们还讨论了针对蛋白质赖氨酸甲基化治疗癌症的潜力和注意事项。
