Chen Yingwei, Jie Wen, Yan Weihui, Zhou Kejun, Xiao Yongtao
Department of Gastroenterology, Shanghai Jiao Tong University, School of Medicine, Xin Hua Hospital, Shanghai, China.
Crit Rev Eukaryot Gene Expr. 2012;22(1):53-9. doi: 10.1615/critreveukargeneexpr.v22.i1.40.
Lysine-specific demethylase 1 (LSD1), the first identified histone demethylase, was belonged to the superfamily of the flavin adenine dinucleotide (FAD)-dependent amine oxidases. LSD1 specifically demethylates mono- or dimethylated dimethylated histone H3 lysine4 (H3K4) and H3 lysine 9 (H3K9) via a redox process. Recently evidences showed that LSD1 played an important role in a broad spectrum of biological processes, including cell proliferation, adipogenesis, spermatogenesis, chromosome segregation and embryonic development. Furthermore, LSD1 also could promote progress of tumor by inhibiting the tumor suppressor activity of p53. To date, as a potential drug for discovering anti-tumor drugs, the medical significance of LSD1 inhibitors have been greatly appreciated. Here, we reviewed the remarkable progress being made in understanding of LSD1, mainly on its structure, basic function and medical application in tumor therapy.
赖氨酸特异性去甲基化酶1（LSD1）是首个被鉴定出的组蛋白去甲基化酶，属于黄素腺嘌呤二核苷酸（FAD）依赖性胺氧化酶超家族。LSD1通过氧化还原过程特异性地使单甲基化或二甲基化的组蛋白H3赖氨酸4（H3K4）和H3赖氨酸9（H3K9）去甲基化。最近的证据表明，LSD1在广泛的生物学过程中发挥重要作用，包括细胞增殖、脂肪生成、精子发生、染色体分离和胚胎发育。此外，LSD1还可通过抑制p53的肿瘤抑制活性促进肿瘤进展。迄今为止，作为发现抗肿瘤药物的潜在药物，LSD1抑制剂的医学意义已得到高度重视。在此，我们综述了在理解LSD1方面取得的显著进展，主要涉及其结构、基本功能以及在肿瘤治疗中的医学应用。
