Nonhistone Lysine Methylation in the Regulation of Cancer Pathways.
Nonhistone Lysine Methylation in the Regulation of Cancer Pathways.
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DOI：
10.1101/cshperspect.a026435
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发表时间：
2016-11-01
影响因子：
5.4
通讯作者：
Gozani O
中科院分区：
文献类型：
--
作者：
Carlson SM;Gozani O
蛋白质受一系列令人难以置信的翻译后修饰（PTM）的调节。组蛋白上赖氨酸残基的甲基化是一种PTM，在调节染色质和表观遗传过程中具有公认的作用。最近发现，数百个和可能数千个非组蛋白的赖氨酸甲基化也开辟了一个巨大的新的研究领域。参与癌症的主要细胞途径，如生长信号和DNA损伤反应，受赖氨酸甲基化调节。虽然该领域近年来发展迅速，但仍有许多基本问题有待解决。本文综述了赖氨酸甲基化的历史和分子功能。然后我们讨论了催化赖氨酸残基甲基化的酶，去除赖氨酸甲基化的酶，以及已知由赖氨酸甲基化调控的癌症途径。文章的其余部分重点关注两个开放的问题，我们建议作为未来研究的路线图。首先是了解大量的候选甲基转移酶和脱甲基酶，其酶活性尚未确定，并且通过遗传研究可能与癌症相关。其次是研究生物学过程和癌症机制可能受到最近发现的大量赖氨酸甲基化位点的调控。
Proteins are regulated by an incredible array of posttranslational modifications (PTMs). Methylation of lysine residues on histone proteins is a PTM with well-established roles in regulating chromatin and epigenetic processes. The recent discovery that hundreds and likely thousands of nonhistone proteins are also methylated at lysine has opened a tremendous new area of research. Major cellular pathways involved in cancer, such as growth signaling and the DNA damage response, are regulated by lysine methylation. Although the field has developed quickly in recent years many fundamental questions remain to be addressed. We review the history and molecular functions of lysine methylation. We then discuss the enzymes that catalyze methylation of lysine residues, the enzymes that remove lysine methylation, and the cancer pathways known tobe regulated by lysine methylation. The rest of the article focuses on two open questions that we suggest as a roadmap for future research. First is understanding the large number of candidate methyltransferase and demethylation enzymes whose enzymatic activity is not yet defined and which are potentially associated with cancer through genetic studies. Second is investigating the biological processes and cancer mechanisms potentially regulated by the multitude of lysine methylation sites that have been recently discovered.
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