Abstract
Recent studies identified an interaction between the Polymerase Associated Factor complex (PAFc) and Mixed Lineage Leukemia (MLL), including MLL-rearranged oncoproteins. This interaction is critical for MLL transcriptional activity and MLL-rearranged leukemogenesis. Here, we discuss the potential molecular role of the PAFc in transcriptional dysregulation of MLL target genes and the interplay between PAFc and MLL-rearranged oncoproteins in leukemogenesis.
Highlights
The mixed lineage leukemia gene Mixed Lineage Leukemia (MLL), the human homolog of the Drosophila trithorax gene, encodes a histone H3 lysine 4 (H3K4) methyltransferase that positively regulates multiple homeobox transcription factors, including Hoxa9 and MEIS1, which are pivotal for leukemogenesis [1]
We found that the Polymerase Associated Factor complex (PAFc) interacts with this region and that this interaction is critical for MLL transcriptional activity as well as leukemogenesis [11, 12]
By mass spectrum analysis, we demonstrated that PAFc interacts with the CxxC-RD2 region of MLL, a region that is always retained in MLL-rearranged oncoproteins
Summary
The mixed lineage leukemia gene MLL, the human homolog of the Drosophila trithorax gene, encodes a histone H3 lysine 4 (H3K4) methyltransferase that positively regulates multiple homeobox transcription factors, including Hoxa9 and MEIS1, which are pivotal for leukemogenesis [1]. We found that the Polymerase Associated Factor complex (PAFc) interacts with this region and that this interaction is critical for MLL transcriptional activity as well as leukemogenesis [11, 12].
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