Author/Authors :
Thiel، نويسنده , , Austin T. and Blessington، نويسنده , , Peter and Zou، نويسنده , , Tao and Feather، نويسنده , , Danielle and Wu، نويسنده , , Xinjiang and Yan، نويسنده , , Jizhou and Zhang، نويسنده , , Hui and Liu، نويسنده , , Zuguo and Ernst، نويسنده , , Patricia and Koretzky، نويسنده , , Gary A. and Hua، نويسنده , , Xianxin، نويسنده ,
Abstract :
Summary
nic fusion proteins are capable of initiating tumorigenesis, but the role of their wild-type counterparts in this process is poorly understood. The mixed lineage leukemia (MLL) gene undergoes chromosomal translocations, resulting in the formation of oncogenic MLL fusion proteins (MLL-FPs). Here, we show that menin recruits both wild-type MLL and oncogenic MLL-AF9 fusion protein to the loci of HOX genes to activate their transcription. Wild-type MLL not only catalyzes histone methylation at key target genes but also controls distinct MLL-AF9-induced histone methylation. Notably, the wild-type Mll allele is required for MLL-AF9-induced leukemogenesis and maintenance of MLL-AF9-transformed cells. These findings suggest an essential cooperation between an oncogene and its wild-type counterpart in MLL-AF9-induced leukemogenesis.
