MLL/WDR5 complex recruits KIF2C to midbody to ensure MT depolymerization and furrow compaction during cytokinesis

Mixed-lineage leukemia (MLL) protein is a well characterized epigenetic regulator whose non-canonical activities remain under appreciated. Here we show that MLL and its associated protein WDR5, localize to the midbody. Loss of MLL/WDR5 results in defective midbody formation, which displays a wide midzone-like microtubule structure, along with chromosome bridges, resulting in binucleated cells. We show that MLL and WDR5 interact with kinesin 13 motor—KIF2C, and targets it to the midbody. The depolymerase activity of KIF2C promotes correct localization of centralspindlin complex, compaction of midzone MTs and finally furrow completion. By characterizing the previously undiscovered role of MLL and KIF2C in the regulation of cytokinesis, our work underscores the importance of these proteins at the interface of actin and microtubule cytoskeleton regulation, pathways that are frequently altered in oncogenesis.