Scoumanne Ariane, Chen Xinbin
Center for Comparative Oncology, University of California at Davis, Davis, California 95616, USA.
J Biol Chem. 2007 May 25;282(21):15471-5. doi: 10.1074/jbc.M701023200. Epub 2007 Apr 4.
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.
赖氨酸特异性去甲基化酶1（LSD1）是几种组蛋白脱乙酰酶复合物的一个组成部分，在染色质重塑和转录调控中发挥重要作用。在此，我们构建了多个可诱导表达或敲低LSD1的细胞系，发现细胞增殖需要LSD1。此外，我们发现LSD1缺陷会导致细胞在G(2)/M期部分停滞，并使细胞对DNA损伤或MDM2抑制诱导的生长抑制敏感，且这种敏感性以p53依赖的方式出现。我们还表明，LSD1缺陷会延迟DNA损伤诱导的p53稳定，导致p21和MDM2的诱导延迟。最后，我们进行了一项微阵列研究，鉴定了几个新的LSD1靶基因，包括编码一种钙结合蛋白的S100A8和一个原癌基因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。
