Cdk1 Coordinates Timely Activation of MKlp2 Kinesin with Relocation of the Chromosome Passenger Complex for Cytokinesis

• DOI: 10.1016/j.celrep.2014.02.034
• Publication Date: 2014-03-22T04:38:49Z
• Authors: Mayumi Kitagawa; Suet Yin Sarah Fung; Umar Farook Shahu...; Hidemasa Goto; Masaki Inagaki; Sang Hyun Lee
• Keywords: 0301 basic medicine; QH301-705.5; Molecular Sequence Data; Kinesins; Mitosis; Cyclin-Dependent Kinases; Genomic Instability; Enzyme Activation; 03 medical and health sciences; CDC2 Protein Kinase; Mutagenesis, Site-Directed; Animals; Humans; Amino Acid Sequence; Biology (General); Cyclin B1; Phosphorylation; Cytokinesis; HeLa Cells

The chromosome passenger complex (CPC) must relocate from anaphase chromosomes to the cell equator for successful cytokinesis. Although this landmark event requires the mitotic kinesin MKlp2, the spatiotemporal mechanistic basis remains elusive. Here, we show that phosphoregulation of MKlp2 by the mitotic kinase Cdk1/cyclin B1 coordinates proper mitotic transition with CPC relocation. We identified multiple Cdk1/cyclin B1 phosphorylation sites within the stalk and C-terminal tail that inhibit microtubule binding and bundling, oligomerization/clustering, and chromosome targeting of MKlp2. Specifically, inhibition of these abilities by Cdk1/cyclin B1 phosphorylation is essential for proper early mitotic progression. Upon anaphase onset, however, reversal of Cdk1/cyclin B1 phosphorylation promotes MKlp2-CPC complex formation and relocates the CPC from anaphase chromosomes for successful cytokinesis. Thus, we propose that phosphoregulation of MKlp2 by Cdk1/cyclin B1 ensures that activation of MKlp2 kinesin and relocation of the CPC occur at the appropriate time and space for proper mitotic progression and genomic stability.