The dimerization domains of MLL are potential therapeutic targets in t(4;11)-leukemias

The human MLL protein – as well as the leukemogenic AF4-MLL fusion protein are specifically hydrolyzed by the endopeptidase Taspase1. The resulting protein fragments are able to form an intramolcular dimer which is necessary for complex formation and stability of both proteins. We have dissected the two dimerization domains, named FYRN and FYRC, by B-2-H experiments, pull-down experiments using recombinant proteins and Co-IP studies in mammalian cells. The minimal interaction domains was experimentally defined as 50 amino acid long peptides that are still able to confer specific binding in vitro and in vivo. Ove…