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Epigenetic roles of MLL oncoproteins are dependent on NF-κB.

Cancer cell (2013-09-24)
Hsu-Ping Kuo, Zhong Wang, Dung-Fang Lee, Masayuki Iwasaki, Jesus Duque-Afonso, Stephen H K Wong, Chiou-Hong Lin, Maria E Figueroa, Jie Su, Ihor R Lemischka, Michael L Cleary
ABSTRACT

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.

MATERIALS
Product Number
Brand
Product Description

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