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IWASAKI Masayuki
Department Research Institutes and Facilities, Research Institutes and Facilities Position Assistant Professor |
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| Article types | Original article |
| Language | English |
| Peer review | Peer reviewed |
| Title | Epigenetic roles of MLL oncoproteins are dependent on NF-κB. |
| Journal | Formal name：Cancer cell Abbreviation：Cancer Cell ISSN code：18783686/15356108 |
| Domestic / Foregin | Foregin |
| Volume, Issue, Page | 24(4),pp.423-37 |
| Author and coauthor | Kuo Hsu-Ping, Wang Zhong, Lee Dung-Fang, Iwasaki Masayuki, Duque-Afonso Jesus, Wong Stephen H K, Lin Chiou-Hong, Figueroa Maria E, Su Jie, Lemischka Ihor R, Cleary Michael L |
| Publication date | 2013/10 |
| Summary | MLL fusion proteins in leukemia induce aberrant transcriptional elongation and associated chromatin perturbations; however, the upstream signaling pathways and activators that recruit or retain MLL oncoproteins at initiated promoters are unknown. Through functional and comparative genomic studies, we identified an essential role for NF-κB signaling in MLL leukemia. Suppression of NF-κB led to robust antileukemia effects that phenocopied loss of functional MLL oncoprotein or associated epigenetic cofactors. The NF-κB subunit RELA occupies promoter regions of crucial MLL target genes and sustains the MLL-dependent leukemia stem cell program. IKK/NF-κB signaling is required for wild-type and fusion MLL protein retention and maintenance of associated histone modifications, providing a molecular rationale for enhanced efficacy in therapeutic targeting of this pathway in MLL leukemias. |
| DOI | 10.1016/j.ccr.2013.08.019 |
| PMID | 24054986 |