MLL/WDR5 complex promotes recruitment of KIF2C to midbody to ensure MT depolymerization and furrow initiation during cytokinesis

Mixed-lineage leukemia (MLL) protein is a well-characterised epigenetic regulator whose non-canonical activities remain underappreciated. MLL has been shown to localize on the midbody and loss of this protein leads to binucleation. However, the critical role of the MLL complex in midbody formation remains underexplored. Here, we further characterize the localization of MLL and its associated protein WDR5 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 target it to the midbody. The depolymerase activity of KIF2C promotes correct localization of centralspindlin complex, compaction of midzone MTs, and finally, timely furrow initiation. Thus, we identify a previously unrecognized role for MLL and KIF2C in cytokinesis regulation. Together with earlier findings, this implicates them in the regulation of actin-microtubule cytoskeleton interface—pathways frequently altered in oncogenesis.