MLL/WDR5 Complex Regulates Kif2A Localization to Ensure Chromosome Congression and Proper Spindle Assembly during Mitosis

Publication date: 19 June 2017
Source:Developmental Cell, Volume 41, Issue 6
Author(s): Aamir Ali, Sailaja Naga Veeranki, Akash Chinchole, Shweta Tyagi
Mixed-lineage leukemia (MLL), along with multisubunit (WDR5, RbBP5, ASH2L, and DPY30) complex catalyzes the trimethylation of H3K4, leading to gene activation. Here, we characterize a chromatin-independent role for MLL during mitosis. MLL and WDR5 localize to the mitotic spindle apparatus, and loss of function of MLL complex by RNAi results in defects in chromosome congression and compromised spindle formation. We report interaction of MLL complex with several kinesin and dynein motors. We further show that the MLL complex associates with Kif2A, a member of the Kinesin-13 family of microtubule depolymerase, and regulates the spindle localization of Kif2A during mitosis. We have identified a conserved WDR5 interaction (Win) motif, so far unique to the MLL family, in Kif2A. The Win motif of Kif2A engages in direct interactions with WDR5 for its spindle localization. Our findings highlight a non-canonical mitotic function of MLL complex, which may have a direct impact on chromosomal stability, frequently compromised in cancer.

Graphical abstract

Teaser

Ali et al. characterize a non-canonical function of the histone methyltransferase family member MLL during mitosis. They find that the MLL complex interacts with kinesin motor protein Kif2A and regulates chromosome alignment and spindle assembly. A "Win" motif in Kif2A directly interacts with WDR5 and regulates its spindle localization.


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