Abstract
The chromosomal passenger complex (CPC) coordinates chromosomal and cytoskeletal events of mitosis. The enzymatic core of this complex (Aurora-B) is guided through the mitotic cell by its companion chromosomal passenger proteins, inner centromere protein (INCENP), Survivin and Borealin/Dasra-B, thereby allowing it to act at the right place at the right time. Here, we addressed the individual contributions of INCENP, Survivin and Borealin to the proper functioning of this complex. We show that INCENP has an important role in stabilizing the complex, and that Borealin acts to promote binding of Survivin to INCENP. Importantly, when Survivin is directly fused to INCENP, this hybrid can restore CPC function at the centromeres and midbody, even in the absence of Borealin and the centromere-targeting domain of INCENP. Thus, Survivin is an important mediator of centromere and midbody docking of Aurora-B during mitosis.
MeSH Terms
Animals
Cell Cycle Proteins/genetics,metabolism
Cell Line
Centromere/metabolism
Chromosomal Proteins, Non-Histone/genetics,metabolism
Cysteine Proteinase Inhibitors/genetics,metabolism
Humans
Inhibitor of Apoptosis Proteins
Macromolecular Substances
Microtubule-Associated Proteins/genetics,metabolism
Mitosis
Neoplasm Proteins/genetics,metabolism
Protein Binding
RNA Interference
RNA, Small Interfering/genetics,metabolism
Recombinant Fusion Proteins/genetics,metabolism
Survivin
Chemicals
BIRC5 protein, human
CDCA8 protein, human
Cell Cycle Proteins
Chromosomal Proteins, Non-Histone
Cysteine Proteinase Inhibitors
INCENP protein, human
Inhibitor of Apoptosis Proteins
Macromolecular Substances
Microtubule-Associated Proteins
Neoplasm Proteins
RNA, Small Interfering
Recombinant Fusion Proteins
Survivin
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Vader Gerben
Division of Molecular Biology, Netherlands Cancer Institute, Amsterdam.
Kauw Jos J W
Medema René H
Lens Susanne M A
References (22)
22 references, click to expand
-
Evidence that the Ipl1-Sli15 (Aurora kinase-INCENP) complex promotes chromosome bi-orientation by altering kinetochore-spindle pole connections.
Cell. 2002 Feb 8;108(3):317-29
PMID: 11853667
-
INCENP is required for proper targeting of Survivin to the centromeres and the anaphase spindle during mitosis.
Curr Biol. 2001 Jun 5;11(11):886-90
PMID: 11516652
-
The small molecule Hesperadin reveals a role for Aurora B in correcting kinetochore-microtubule attachment and in maintaining the spindle assembly checkpoint.
J Cell Biol. 2003 Apr 28;161(2):281-94
PMID: 12707311
-
CSC-1: a subunit of the Aurora B kinase complex that binds to the survivin-like protein BIR-1 and the incenp-like protein ICP-1.
J Cell Biol. 2003 Apr 28;161(2):229-36
PMID: 12707312
-
Aurora B couples chromosome alignment with anaphase by targeting BubR1, Mad2, and Cenp-E to kinetochores.
J Cell Biol. 2003 Apr 28;161(2):267-80
PMID: 12719470
-
Survivin is required for a sustained spindle checkpoint arrest in response to lack of tension.
EMBO J. 2003 Jun 16;22(12):2934-47
PMID: 12805209
-
Exploring the functional interactions between Aurora B, INCENP, and survivin in mitosis.
Mol Biol Cell. 2003 Aug;14(8):3325-41
PMID: 12925766
-
The survivin/Aurora B complex: its role in coordinating tension and attachment.
Cell Cycle. 2003 Nov-Dec;2(6):507-10
PMID: 14504461
-
Aurora-B phosphorylation in vitro identifies a residue of survivin that is essential for its localization and binding to inner centromere protein (INCENP) in vivo.
J Biol Chem. 2004 Feb 13;279(7):5655-60
PMID: 14610074
-
Autophosphorylation of a newly identified site of Aurora-B is indispensable for cytokinesis.
J Biol Chem. 2004 Mar 26;279(13):12997-3003
PMID: 14722118
-
Correcting improper chromosome-spindle attachments during cell division.
Nat Cell Biol. 2004 Mar;6(3):232-7
PMID: 14767480
-
The chromosomal passenger complex is required for chromatin-induced microtubule stabilization and spindle assembly.
Cell. 2004 Jul 23;118(2):187-202
PMID: 15260989
-
Borealin: a novel chromosomal passenger required for stability of the bipolar mitotic spindle.
J Cell Biol. 2004 Jul 19;166(2):179-91
PMID: 15249581
-
Chromosomal passengers: the four-dimensional regulation of mitotic events.
Chromosoma. 2004 Nov;113(5):211-22
PMID: 15351889
-
How cells get the right chromosomes.
Science. 1997 Jan 31;275(5300):632-7
PMID: 9005842
-
INCENP centromere and spindle targeting: identification of essential conserved motifs and involvement of heterochromatin protein HP1.
J Cell Biol. 1998 Dec 28;143(7):1763-74
PMID: 9864353
-
The budding yeast protein kinase Ipl1/Aurora allows the absence of tension to activate the spindle checkpoint.
Genes Dev. 2001 Dec 1;15(23):3118-29
PMID: 11731476
-
Polo-like kinase-1 is a target of the DNA damage checkpoint.
Nat Cell Biol. 2000 Sep;2(9):672-6
PMID: 10980711
-
INCENP binds the Aurora-related kinase AIRK2 and is required to target it to chromosomes, the central spindle and cleavage furrow.
Curr Biol. 2000 Sep 7;10(17):1075-8
PMID: 10996078
-
The aurora-related kinase AIR-2 recruits ZEN-4/CeMKLP1 to the mitotic spindle at metaphase and is required for cytokinesis.
Curr Biol. 2000 Oct 5;10(19):1162-71
PMID: 11050384
-
Incenp and an aurora-like kinase form a complex essential for chromosome segregation and efficient completion of cytokinesis.
Curr Biol. 2000 Oct 5;10(19):1172-81
PMID: 11050385
-
Bi-orienting chromosomes on the mitotic spindle.
Curr Opin Cell Biol. 2002 Jun;14(3):365-71
PMID: 12067660