Borealin: a novel chromosomal passenger required for stability of the bipolar mitotic spindle.
The chromosomal passenger complex of Aurora B kinase, INCENP, and Survivin has essential regulatory roles at centromeres and the central spindle in mitosis. Here, we describe Borealin, a novel member of the complex. Approximately half of Aurora B in mitotic cells is complexed with INCENP, Borealin, and Survivin; and Borealin binds Survivin and INCENP in vitro. A second complex contains Aurora B and INCENP, but no Borealin or Survivin. Depletion of Borealin by RNA interference delays mitotic progression and results in kinetochore-spindle misattachments and an increase in bipolar spindles associated with ectopic asters. The extra poles, which apparently form after chromosomes achieve a bipolar orientation, severely disrupt the partitioning of chromosomes in anaphase. Borealin depletion has little effect on histone H3 serine10 phosphorylation. These results implicate the chromosomal passenger holocomplex in the maintenance of spindle integrity and suggest that histone H3 serine10 phosphorylation is performed by an Aurora B-INCENP subcomplex.
Gassmann
Reto
R
Wellcome Trust Centre for Cell Biology, School of Biological Sciences, University of Edinburgh, Kings Buildings, Mayfield Rd., Edinburgh EH9 3JR, Scotland, UK.
Carvalho
Ana
A
Henzing
Alexander J
AJ
Ruchaud
Sandrine
S
Hudson
Damien F
DF
Honda
Reiko
R
Nigg
Erich A
EA
Gerloff
Dietlind L
DL
Earnshaw
William C
WC
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D002455:Cell Division; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism; D002875:Chromosomes; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D046911:Macromolecular Substances; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009154:Mutation; D009363:Neoplasm Proteins; D009687:Nuclear Proteins / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics; D016415:Sequence Alignment; D008941:Spindle Apparatus; D000077022:Survivin
C107489:BIRC5 protein, human; C490157:CDCA8 protein, human; D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; C083767:INCENP protein, human; D051034:Inhibitor of Apoptosis Proteins; D046911:Macromolecular Substances; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D011993:Recombinant Fusion Proteins; D000077022:Survivin