INCENP-aurora B interactions modulate kinase activity and chromosome passenger complex localization.
Dynamic localization of the chromosomal passenger complex (CPC) during mitosis is essential for its diverse functions. CPC targeting to centromeres involves interactions between Survivin, Borealin, and the inner centromere protein (CENP [INCENP]) N terminus. In this study, we investigate how interactions between the INCENP C terminus and aurora B set the level of kinase activity. Low levels of kinase activity, seen in INCENP-depleted cells or in cells expressing a mutant INCENP that cannot bind aurora B, are sufficient for a spindle checkpoint response when microtubules are absent but not against low dose taxol. Intermediate kinase activity levels obtained with an INCENP mutant that binds aurora B but cannot fully activate it are sufficient for a robust response against taxol, but cannot trigger CPC transfer from the chromosomes to the anaphase spindle midzone. This transfer requires significantly higher levels of aurora B activity. These experiments reveal that INCENP interactions with aurora B in vivo modulate the level of kinase activity, thus regulating CPC localization and functions during mitosis.
Xu
Zhenjie
Z
Wellcome Trust Centre for Cell Biology, University of Edinburgh, Edinburgh EH9 3JR, Scotland, UK.
Ogawa
Hiromi
H
Vagnarelli
Paola
P
Bergmann
Jan H
JH
Hudson
Damien F
DF
Ruchaud
Sandrine
S
Fukagawa
Tatsuo
T
Earnshaw
William C
WC
Samejima
Kumiko
K
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D064127:Aurora Kinases; D002460:Cell Line; D002503:Centromere / Q000378:metabolism*; D002645:Chickens; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D004789:Enzyme Activation / Q000235:genetics; D008870:Microtubules / Q000502:physiology; D008938:Mitosis / Q000502:physiology; D008969:Molecular Sequence Data; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D016415:Sequence Alignment; D008941:Spindle Apparatus / Q000502:physiology / Q000648:ultrastructure
D002868:Chromosomal Proteins, Non-Histone; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases