Polo-like kinase 1 triggers the initiation of cytokinesis in human cells by promoting recruitment of the RhoGEF Ect2 to the central spindle.
Cytokinesis of animal cells requires ingression of the actomyosin-based contractile ring between segregated sister genomes. Localization of the RhoGEF Ect2 to the central spindle at anaphase promotes local activation of the RhoA GTPase, which induces assembly and ingression of the contractile ring. Here we have used BI 2536, an inhibitor of the mitotic kinase Plk1, to analyze the functions of this enzyme during late mitosis in human cells. We show that Plk1 acts after Cdk1 inactivation and independently from Aurora B to promote RhoA accumulation at the equator, contractile ring formation, and cleavage furrow ingression. Inhibition of Plk1 abolishes the interaction of Ect2 with its activator and midzone anchor, HsCyk-4, thereby preventing localization of Ect2 to the central spindle. We propose that late mitotic Plk1 activity promotes recruitment of Ect2 to the central spindle, triggering the initiation of cytokinesis and contributing to cleavage plane specification in human cells.
Petronczki
Mark
M
Research Institute of Molecular Pathology, A-1030 Vienna, Austria.
Glotzer
Michael
M
Kraut
Norbert
N
Peters
Jan-Michael
JM
D064107:Aurora Kinase B; D064127:Aurora Kinases; D016203:CDC2 Protein Kinase / Q000378:metabolism; D002384:Catalysis / Q000187:drug effects; D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002877:Chromosomes, Human / Q000235:genetics; D048749:Cytokinesis / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008954:Models, Biological; D011485:Protein Binding / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D021381:Protein Transport / Q000187:drug effects; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011621:Pteridines / Q000494:pharmacology; D064067:Rho Guanine Nucleotide Exchange Factors; D008941:Spindle Apparatus / Q000187:drug effects / Q000378:metabolism*; D020742:rhoA GTP-Binding Protein / Q000378:metabolism; D000097869:Polo-Like Kinase 1
D064107:Aurora Kinase B; D064127:Aurora Kinases; D016203:CDC2 Protein Kinase; D018797:Cell Cycle Proteins; D020662:Guanine Nucleotide Exchange Factors; D008869:Microtubule-Associated Proteins; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D011621:Pteridines; D064067:Rho Guanine Nucleotide Exchange Factors; D020742:rhoA GTP-Binding Protein; D000097869:Polo-Like Kinase 1; C518477:BI 2536; C489850:ECT2 protein, human; C576921:AURKB protein, human