کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2107698 | 1083695 | 2010 | 12 صفحه PDF | دانلود رایگان |
SummaryOncogenic 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.
Graphical AbstractFigure optionsDownload high-quality image (167 K)Download as PowerPoint slideHighlights
► Menin recruits both wild-type MLL protein and MLL-AF9 to loci of HOX genes
► Wild-type MLL controls both H3K4 methylation and MLL-AF9-induced H3K79 methylation
► Wild-type MLL allele is required for MLL-AF9-induced leukemogenesis
► Wild-type MLL is crucial for maintenance of MLL-AF9-transformed leukemia cells
Journal: - Volume 17, Issue 2, 17 February 2010, Pages 148–159