INCENP is required for proper targeting of Survivin to the centromeres and the anaphase spindle during mitosis

  title={INCENP is required for proper targeting of Survivin to the centromeres and the anaphase spindle during mitosis},
  author={Sally P. Wheatley and Ana Carvalho and Paola Vagnarelli and William C. Earnshaw},
  journal={Current Biology},

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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*

It is reported that human survivin is specifically phosphorylated in vitro by aurora-B kinase at threonine 117 in its carboxyl α-helical coil, suggesting that phosphorylation of survivin at threxine 117 by aur Nora-B may regulate targeting of Survivin, and possibly the entire passenger complex, in mammals.

Aurora B kinase exists in a complex with survivin and INCENP and its kinase activity is stimulated by survivin binding and phosphorylation.

The data indicate that Aurora B kinase activity is regulated by both Survivin binding and cell cycle-dependent phosphorylation, and the hydrodynamic properties of the Aurora B/Survivin/INCENP complex are cell cycle regulated.

Exploring the functional interactions between Aurora B, INCENP, and survivin in mitosis.

It is found that overexpression of a catalytically inactive, dominant-negative mutant of Aurora B impaired the localization of the entire Aurora B/INCENP/survivin complex to centromeres and the central spindle and severely disturbed mitotic progression.

Perturbation of Incenp function impedes anaphase chromatid movements and chromosomal passenger protein flux at centromeres

New mitotic roles for the CPC in anaphase are uncovered and it is proposed that CPC turnover at centromeres modulates spindle assembly checkpoint signaling.

Relocation of Aurora B from centromeres to the central spindle at the metaphase to anaphase transition requires MKlp2

It is proposed that MKlp2 is involved in the localization of Plk1, Aurora B, and Cdc14A to the central spindle during anaphase, and that the integration of signaling by these proteins is necessary for proper cytokinesis.

Survivin mediates targeting of the chromosomal passenger complex to the centromere and midbody

It is shown that INCENP has an important role in stabilizing the complex, and that Borealin acts to promote binding of Survivin to INCenP, which means Survivin is an important mediator of centromere and midbody docking of Aurora‐B during mitosis.

Borealin: a novel chromosomal passenger required for stability of the bipolar mitotic spindle.

Borealin is described and 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.

Overexpression of an Aurora-C kinase-deficient mutant disrupts the Aurora-B/INCENP complex and induces polyploidy.

Immunofluorescence analysis of ectopically expressed GFP-Aurora-C has revealed that Aurora-C is a new member of the chromosomal passenger proteins localizing first to the centromeres and then to the central spindles during cytokinesis, suggesting that it may serve as a key regulator in cell division.

Targeting the INCENP IN-box–Aurora B interaction to inhibit CPC activity in vivo

It is shown that overexpression of soluble IN-box in HeLa cells affects endogenous CPC localization and produces a significant increase in multinucleated and micronucleated cells consistent with CPC loss of function.



Essential Roles of Drosophila Inner Centromere Protein (Incenp) and Aurora B in Histone H3 Phosphorylation, Metaphase Chromosome Alignment, Kinetochore Disjunction, and Chromosome Segregation

It is revealed that INCENP is required for aurora B kinase function and confirmed that the chromosomal passengers have essential roles in mitosis.

Human Survivin Is a Kinetochore-Associated Passenger Protein

It is concluded that human survivin is positioned to have an important function in the mechanism of cell cleavage.

A Dominant Mutant of Inner Centromere Protein (INCENP), a Chromosomal Protein, Disrupts Prometaphase Congression and Cytokinesis

Experiments provide evidence of an unexpected link between this chromosomal protein and cytokinesis, and suggest that one function of INCENP may be to integrate the chromosomal and cytoskeletal events of mitosis.

INCENP binds directly to tubulin and requires dynamic microtubules to target to the cleavage furrow.

Yeast two-hybrid and in vitro binding data demonstrate that INCENP binds directly to beta-tubulin via a conserved domain encompassing residues 48-85 and appears to bundle microtubules when expressed in the interphase cytoplasm, indicating that INCenP is a microtubule-binding protein that targets to the equatorial cortex through interactions requiring micro Tubulin.

AIR-2: An Aurora/Ipl1-related Protein Kinase Associated with Chromosomes and Midbody Microtubules Is Required for Polar Body Extrusion and Cytokinesis in Caenorhabditis elegans Embryos

The results suggest that during each meiotic and mitotic division, AIR-2 may coordinate the congression of metaphase chromosomes with the subsequent events of polar body extrusion and cytokinesis.