The lysine-specific demethylase 1 is required for cell proliferation in both p53-dependent and -independent manners.
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.
Scoumanne
Ariane
A
Center for Comparative Oncology, University of California at Davis, Davis, California 95616, USA.
Chen
Xinbin
X
D040501:Calgranulin A / Q000096:biosynthesis / Q000235:genetics; D002455:Cell Division / Q000502:physiology*; D045744:Cell Line, Tumor; D042002:Chromatin Assembly and Disassembly / Q000502:physiology*; D002868:Chromosomal Proteins, Non-Histone / Q000096:biosynthesis / Q000235:genetics; D004249:DNA Damage / Q000235:genetics; D016195:G2 Phase / Q000502:physiology*; D020869:Gene Expression Profiling; D056466:Histone Demethylases; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D015513:Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics; D010089:Oxidoreductases, N-Demethylating / Q000172:deficiency / Q000378:metabolism*; D000075223:Poly-ADP-Ribose Binding Proteins; D000090063:Proto-Oncogene Mas; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
D040501:Calgranulin A; D002868:Chromosomal Proteins, Non-Histone; C084738:DEK protein, human; C000715470:MAS1 protein, human; D015513:Oncogene Proteins; D000075223:Poly-ADP-Ribose Binding Proteins; D000090063:Proto-Oncogene Mas; D016159:Tumor Suppressor Protein p53; D056466:Histone Demethylases; C495195:KDM1A protein, human; D010089:Oxidoreductases, N-Demethylating; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2