Complex formation of Plk1 and INCENP required for metaphase-anaphase transition.
Mitotic chromosomal dynamics is regulated by the coordinated activities of many mitotic kinases, such as cyclin-dependent kinase 1 (Cdk1), Aurora-B or Polo-like kinase 1 (Plk1), but the mechanisms of their coordination remain unknown. Here, we report that Cdk1 phosphorylates Thr 59 and Thr 388 on inner centromere protein (INCENP), which regulates the localization and kinase activity of Aurora-B from prophase to metaphase. INCENP depletion disrupts Plk1 localization specifically at the kinetochore. This phenotype is rescued by the exogenous expression of INCENP wild type and INCENP mutated at Thr 59 to Ala (T59A), but not at Thr 388 to Ala (T388A). The replacement of endogenous INCENP with T388A resulted in the delay of progression from metaphase to anaphase. We propose that INCENP phosphorylation by Cdk1 is necessary for the recruitment of Plk1 to the kinetochore, and that the complex formation of Plk1 and Aurora-B on INCENP may play crucial roles in the regulation of chromosomal dynamics.
Goto
Hidemasa
H
Division of Biochemistry, Aichi Cancer Center Research Institute, Nagoya, Aichi 464-8681, Japan.
Kiyono
Tohru
T
Tomono
Yasuko
Y
Kawajiri
Aie
A
Urano
Takeshi
T
Furukawa
Koichi
K
Nigg
Erich A
EA
Inagaki
Masaki
M
D000595:Amino Acid Sequence; D000705:Anaphase / Q000502:physiology*; D000818:Animals; D064107:Aurora Kinase B; D064127:Aurora Kinases; D016203:CDC2 Protein Kinase / Q000378:metabolism; D019556:COS Cells; D018797:Cell Cycle Proteins / Q000378:metabolism*; D048750:Cell Nucleus Division / Q000502:physiology; D018385:Centrosome / Q000378:metabolism; D002522:Chlorocebus aethiops; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D018386:Kinetochores / Q000378:metabolism; D008677:Metaphase / Q000502:physiology*; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008954:Models, Biological; D009154:Mutation / Q000235:genetics; D009363:Neoplasm Proteins / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D017386:Sequence Homology, Amino Acid; D000077022:Survivin; D014162:Transfection; D000097869:Polo-Like Kinase 1
D064107:Aurora Kinase B; D064127:Aurora Kinases; D016203:CDC2 Protein Kinase; D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D034741:RNA, Small Interfering; D000077022:Survivin; D000097869:Polo-Like Kinase 1; C107489:BIRC5 protein, human; C083767:INCENP protein, human; C513185:Incenp protein, mouse; C576921:AURKB protein, human; C576924:Aurkb protein, mouse