title: Mad2 inhibits the mitotic kinesin MKlp2.
abstract: We identified the mitotic kinesin-like protein 2 (MKlp2), a kinesin required for chromosome passenger complex (CPC)-mediated cytokinesis, as a target of the mitotic checkpoint protein Mad2. MKlp2 possesses a consensus Mad2-binding motif required for Mad2 binding. Mad2 prevents MKlp2 from loading onto the mitotic spindle, a prerequisite step for its function as a mitotic kinesin. Furthermore, Mad2 inhibits the ability of MKlp2 to relocate the CPC from centromeres, an essential step to promote cytokinesis. An MKlp2 mutant that is refractory to Mad2-mediated inhibition prematurely translocates to the mitotic spindle and mislocalizes the CPC component Aurora B from the midbody of dividing cells. This correlates with an increased incidence of cytokinesis failure. Together, these findings reveal that MKlp2 is a novel mitotic target of Mad2 necessary for proper mitotic progression and cytokinesis.
authors.affiliation: Program in Cancer and Stem Cell Biology, Graduate Medical School, Duke-National University of Singapore, 169857 Singapore. hsaya@a5.keio.jp
authors.forename: Sang Hyun
authors.initials: SH
authors.lastname: Lee
authors.forename: Frank
authors.initials: F
authors.lastname: McCormick
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Saya
mesh_terms: D000595:Amino Acid Sequence; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D006367:HeLa Cells; D006801:Humans; D016547:Kinesins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D064246:Mad2 Proteins; D008969:Molecular Sequence Data; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
chemical_list: D002135:Calcium-Binding Proteins; D018797:Cell Cycle Proteins; C410089:KIF20A protein, human; C577697:MAD2L1 protein, human; D064246:Mad2 Proteins; D012097:Repressor Proteins; D016547:Kinesins