过去的十年中对于组蛋白和非组蛋白如p53、NF-κB和E2F1蛋白的赖氨酸残基的甲基化/去甲基化作用的研究非常多。这些'阴-阳'的翻译后修饰能够精细地微调这些蛋白质的活性。赖氨酸的甲基化和去甲基化是由蛋白赖氨酸甲基转移（PKMTs）及蛋白赖氨酸去甲基化酶（PKDMs）催化完成的。PKMTs、PKDMs以及它们的底物在癌症中有着重要的作用。虽然肿瘤发生的基本机制仍然知之甚少，越来越多的证据表明甲基化的异常调节和肿瘤发生有着密切的关系。这篇文章综述了蛋白质的赖氨酸甲基化的生物学功能研究以及针对PKMTs和PKDMs的小分子抑制剂的研究中的一些新进展，同时还讨论了以赖氨酸甲基化为靶点进行癌症治疗的可能性和难点。

图例1 p53的赖氨酸甲基化位点

Targeting protein lysine methylation and demethylation in cancers

Yunlong He, Ilia Korboukh, Jian Jin, and Jing Huang

Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA

During the last decade, we saw an explosion of studies investigating the role of lysinemethylation/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. Lysinemethylation and demethylation are catalyzed by proteinlysine 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 proteinlysinemethylation, and in the discovery of small molecule inhibitors for PKMTs and PKDMs. We also discuss the potential and the caveats of targetingproteinlysinemethylation for the treatment of cancer.

Acta Biochim Biophys Sin (Shanghai). 2012 Jan;44(1):70-9. doi: 10.1093/abbs/gmr109.

全文: http://abbs.oxfordjournals.org/content/44/1/70.full.pdf+html