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Targeting MLL1 H3K4 Methyltransferase Activity in Mixed-Lineage Leukemia
文献类型：期刊论文
| 作者 | Cao, F; Townsend, EC; Karatas, H; Xu, J; Li, L; Lee, S; Liu, L; Chen, Y; Ouillette, P; Zhu, JD |
| 刊名 | MOLECULAR CELL
 |
| 出版日期 | 2014 |
| 卷号 | 53期号:2页码:247-261 |
| 通讯作者 | Wang, SM (reprint author), Univ Michigan, Dept Med Chem, Ann Arbor, MI 48109 USA.,shaomeng@umich.edu |
| 英文摘要 | Here we report a comprehensive characterization of our recently developed inhibitor MM-401 that targets the MLL1 H3K4 methyltransferase activity. MM-401 is able to specifically inhibit MLL1 activity by blocking MLL1-WDR5 interaction and thus the complex assembly. This targeting strategy does not affect other mixed-lineage leukemia (MLL) family histone methyltransferases (HMTs), revealing a unique regulatory feature for the MLL1 complex. Using MM-401 and its enantiomer control MM-NC-401, we show that inhibiting MLL1 methyltransferase activity specifically blocks proliferation of MLL cells by inducing cell-cycle arrest, apoptosis, and myeloid differentiation without general toxicity to normal bone marrow cells or non-MLL cells. More importantly, transcriptome analyses show that MM-401 induces changes in gene expression similar to those of MLL1 deletion, supporting a predominant role of MLL1 activity in regulating MLL1-dependent leukemia transcription program. We envision broad applications for MM-401 in basic and translational research. |
| 学科主题 | Biochemistry & Molecular Biology ; Cell Biology |
| 类目[WOS] | Biochemistry & Molecular Biology ; Cell Biology |
| 关键词[WOS] | TRANSCRIPTIONAL REGULATION ; HISTONE METHYLTRANSFERASE ; FUSION PROTEINS ; METHYLATION ; COMPLEX ; WDR5 ; LEUKEMOGENESIS ; HEMATOPOIESIS ; MECHANISMS ; INHIBITION |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000330496400008 |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.143/handle/331003/151]  |
| 专题 | 上海生化细胞研究所_上海生科院生化细胞研究所 |
| 推荐引用方式 GB/T 7714 | Cao, F,Townsend, EC,Karatas, H,et al. Targeting MLL1 H3K4 Methyltransferase Activity in Mixed-Lineage Leukemia[J]. MOLECULAR CELL,2014,53(2):247-261. |
| APA | Cao, F.,Townsend, EC.,Karatas, H.,Xu, J.,Li, L.,...&Dou, YL.(2014).Targeting MLL1 H3K4 Methyltransferase Activity in Mixed-Lineage Leukemia.MOLECULAR CELL,53(2),247-261. |
| MLA | Cao, F,et al."Targeting MLL1 H3K4 Methyltransferase Activity in Mixed-Lineage Leukemia".MOLECULAR CELL 53.2(2014):247-261. |
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