The lysine-specific demethylase 1 is required for cell proliferation in both p53-dependent and -independent manners
The lysine-specific demethylase 1 is required for cell proliferation in both p53-dependent and -independent manners
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DOI：
10.1074/jbc.m701023200
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发表时间：
2007-05-25
影响因子：
4.8
通讯作者：
Chen, Xinbin
中科院分区：
文献类型：
--
作者：
Scoumanne, Ariane;Chen, Xinbin
赖氨酸特异性去甲基化酶1 （LSD1）是多种组蛋白去乙酰化酶复合物的组成部分，在染色质重塑和转录调控中起重要作用。在这里，我们生成了多个LSD1被诱导表达或敲低的细胞系，发现LSD1是细胞增殖所必需的。此外，我们发现LSD1的缺失导致G(2)/M部分细胞周期阻滞，并以p53依赖的方式使细胞对DNA损伤或MDM2抑制诱导的生长抑制敏感。我们还发现LSD1缺陷延迟了DNA损伤诱导的p53稳定，导致p21和MDM2的延迟诱导。最后，我们进行了微阵列研究，并鉴定了几个新的LSD1靶基因，包括编码钙结合蛋白的S100A8和原癌基因DEK。综上所述，我们发现LSD1通过调节促生存基因表达和p53转录活性具有促癌功能。
The lysine-specific demethylase 1 (LSD1), a component of several histone deacetylase complexes, plays an important role in chromatin remodeling and transcriptional regulation. Here, we generated multiple cell lines in which LSD1 is inducibly expressed or knocked down and found that LSD1 is required for cell proliferation. In addition, we found that deficiency in LSD1 leads to a partial cell cycle arrest in G(2)/M and sensitizes cells to growth suppression induced by DNA damage or MDM2 inhibition in a p53-dependent manner. We also showed that LSD1 deficiency delays p53 stabilization induced by DNA damage, leading to a delayed induction of p21 and MDM2. Finally, we performed a microarray study and identified several novel LSD1 target genes, including S100A8, which encodes a calcium-binding protein, and DEK, a proto-oncogene. Taken together, we uncovered that LSD1 has a pro-oncogenic function by modulating pro-survival gene expression and p53 transcriptional activity.