Max-Planck Institute of Immunobiology and Epigenetics in Freiburg, Germany.
Brief Funct Genomics. 2013 May;12(3):231-43. doi: 10.1093/bfgp/els065. Epub 2013 Jan 15.
Lysine N-ε-acetylation is a post-translational modification that regulates the function of histone and non-histone proteins. In several malignancies, histone acetyltransferase (HAT) activities are disturbed as a consequence of various genetic or epigenetic alterations. In particular, HATs can function as tumor suppressors, helping cells control cellular proliferation and cell cycle, and also as oncogenes, because abnormal acetylation can activate malignant proteins and contribute to cancer. An impaired acetylation profile can be indicative of a pathological process, and thus evaluation of histone acetylation could be used as a predictive index of patient survival or therapy outcome. Therefore, epigenetic therapy might be a very effective strategy to defeat cancer. With the use of histone deacetylase inhibitors and acetylation modulators (e.g. HAT inhibitors, bromodomain inhibitors), we are paving the way for a future epigenetic drug control of human diseases.
赖氨酸 N-ε-乙酰化是一种翻译后修饰，可调节组蛋白和非组蛋白的功能。在几种恶性肿瘤中，由于各种遗传或表观遗传改变，组蛋白乙酰转移酶 (HAT) 的活性受到干扰。特别是，HAT 可以作为肿瘤抑制因子发挥作用，帮助细胞控制细胞增殖和细胞周期，也可以作为癌基因，因为异常乙酰化可以激活恶性蛋白并导致癌症。乙酰化谱的改变可能表明存在病理过程，因此评估组蛋白乙酰化可以作为预测患者生存或治疗结果的指标。因此，表观遗传治疗可能是战胜癌症的非常有效的策略。通过使用组蛋白去乙酰化酶抑制剂和乙酰化调节剂（例如 HAT 抑制剂、溴结构域抑制剂），我们正在为未来人类疾病的表观遗传药物控制铺平道路。
