The Zinc Finger Transcription Factor Mds1‐Evi1 Forms a Novel Protein Complex in MLL leukemia

TL;DRAbstract

The dual transcription factor‐methyltransferase Mds1‐Evi1 is frequently overexpressed in high‐risk leukemias. Mds1‐Evi1 contributes to leukemias induced by the mixed lineage leukemia (MLL) fusion protein MLL‐AF9, although the mechanism is unknown. MLL contains chromatin‐targeting and histone lysine methyltransferase domains, and fusion to AF9 can cause aberrant protein recruitment to target genes. Although Mds1‐Evi1 contains a methyltransferase domain, it does not appear to act on histones. Therefore, we are interested in how protein‐protein interactions involving Mds1‐Evi1 contribute to leukemogenesis. Many known interactors of MLL and Mds1‐Evi1 include chromatin modifying enzymes, suggesting that coordination between epigenetic modulators is key in leukemia pathogenesis. Here, we report the biochemical purification of a novel Mds1‐Evi1‐containing protein complex using a unique murine model of leukemia. To isolate the complex, we induced acute MLL‐AF9 leukemia in mice containing a tan

Chat with Paper

AI Agents for this Paper