Autophosphorylation of a newly identified site of Aurora-B is indispensable for cytokinesis.
Mitotic kinases regulate cell division and its checkpoints, errors of which can lead to aneuploidy or genetic instability. One of these is Aurora-B, a key kinase that is required for chromosome alignment at the metaphase plate and for cytokinesis in mammalian cells. We report here that human Aurora-B is phosphorylated at Thr-232 through interaction with the inner centromere protein (INCENP) in vivo. The phosphorylation of Thr-232 occurs by means of an autophosphorylation mechanism, which is indispensable for the Aurora-B kinase activity. The activation of Aurora-B spatio-temporally correlated with the site-specific phosphorylation of its physiological substrates, histone H3 and vimentin. Overexpression of the TA mutant of Aurora-B, in which Thr-232 was changed into alanine, frequently induced multinuclearity in cells. These results indicate that the phosphorylation of Thr-232 is an essential regulatory mechanism for Aurora-B activation.
Yasui
Yoshihiro
Y
Division of Biochemistry, Aichi Cancer Center Research Institute, Chikusa-ku, Nagoya, Aichi 464-8681, Japan.
Urano
Takeshi
T
Kawajiri
Aie
A
Nagata
Koh-ichi
K
Tatsuka
Masaaki
M
Saya
Hideyuki
H
Furukawa
Koichi
K
Takahashi
Toshitada
T
Izawa
Ichiro
I
Inagaki
Masaki
M
D000409:Alanine / Q000737:chemistry; D000595:Amino Acid Sequence; D000818:Animals; D064107:Aurora Kinase B; D064127:Aurora Kinases; D001665:Binding Sites; D019556:COS Cells; D002455:Cell Division; D002467:Cell Nucleus / Q000378:metabolism; D002875:Chromosomes / Q000648:ultrastructure; D006367:HeLa Cells; D006657:Histones / Q000737:chemistry; D006801:Humans; D013058:Mass Spectrometry; D008856:Microscopy, Fluorescence; D008938:Mitosis; D008969:Molecular Sequence Data; D009154:Mutation; D010766:Phosphorylation; D010957:Plasmids / Q000378:metabolism; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry*; D017386:Sequence Homology, Amino Acid; D013912:Threonine / Q000737:chemistry; D013997:Time Factors; D014162:Transfection; D014746:Vimentin / Q000737:chemistry
D006657:Histones; D014746:Vimentin; D013912:Threonine; C576921:AURKB protein, human; D064107:Aurora Kinase B; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases; D000409:Alanine