Affinage

INCENP

Inner centromere protein · UniProt Q9NQS7

Length
918 aa
Mass
105.4 kDa
Annotated
2026-06-10
80 papers in source corpus 41 papers cited in narrative 42 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

INCENP is the scaffold subunit of the chromosomal passenger complex (CPC), an evolutionarily conserved machine that coordinates chromosome segregation and cytokinesis by positioning and activating Aurora B kinase across mitosis; it localizes to the inner centromere through metaphase and then transfers to the central spindle, contractile ring, and midbody (PMID:3316246, PMID:10996078). INCENP is modular: its N-terminal 58 residues form a three-helix bundle with Survivin and Borealin that is essential and sufficient to target the CPC to inner centromeres independently of Aurora B kinase activity (PMID:16571674, PMID:17956729), while its conserved C-terminal IN-box directly binds Aurora B (and the related Aurora C) and is required to localize the kinase to centromeres and the central spindle (PMID:10996078, PMID:15316025). Binding within this complex allosterically activates Aurora B—the IN-box forms a crown around the kinase small lobe to induce the active T-loop conformation (PMID:15866179)—and Aurora B in turn phosphorylates the INCENP TSS motif (Thr893/Ser894/Ser895), driving a positive-feedback loop that yields the fully active kinase (PMID:12048181, PMID:12925766, PMID:31320618). The central single-alpha-helix (SAH) domain of INCENP directly binds microtubules and acts as a flexible 'dog-leash' spacer that lets centromere-anchored Aurora B reach outer kinetochore substrates, with this microtubule affinity tuned by CDK phosphorylation of flanking segments (PMID:26175154, PMID:28314740). Through these activities the CPC promotes chromosome bi-orientation by destabilizing erroneous kinetochore–microtubule attachments (PMID:11853667), protects centromeric cohesion via substrates such as MEI-S332 (PMID:16824953), and directs central-spindle and midbody assembly by recruiting kinesins MKLP1 and Plk1 (PMID:16378098, PMID:15796717). Relocation from centromeres to the spindle midzone at anaphase is governed by INCENP phosphoregulation: Cdc14 phosphatase, activated by separase, dephosphorylates INCENP/Sli15 to trigger transfer and silence the mitotic checkpoint (PMID:14605209, PMID:20619650), and an electrostatic microtubule-binding switch coupled to H2A dephosphorylation drives the localization change (PMID:26166576). Additional regulatory inputs include Cdk1 phosphorylation controlling Plk1 recruitment (PMID:16378098), Chk2 phosphorylation of Ser91 imposing the abscission checkpoint through Mklp2 binding (PMID:33355621), and PRMT1 methylation of Arg887 that lowers Aurora B binding affinity (PMID:26460953).

Mechanistic history

Synthesis pass · year-by-year structured walk · 21 steps
  1. 1987 High

    Established the existence and dynamic behavior of an inner centromere protein that relocates from chromosomes to the spindle and midbody, defining the phenomenon the gene is named for.

    Evidence Monoclonal antibody immunofluorescence and chromosome scaffold fractionation of mitotic cells

    PMID:3316246

    Open questions at the time
    • No molecular partners or biochemical activity identified
    • Mechanism of relocation unknown
  2. 1998 High

    Mapped INCENP into discrete functional modules, localizing centromere/midbody targeting to the N-terminus and revealing that centromere association is functionally coupled to downstream cytoskeletal events.

    Evidence GFP-tagged truncation/deletion mutagenesis, yeast two-hybrid, and dominant-negative expression in cultured cells

    PMID:9490714 PMID:9864353

    Open questions at the time
    • HP1 interaction not linked to a function
    • Microtubule region not yet characterized molecularly
  3. 2000 High

    Identified INCENP as the direct binding partner and localization determinant for Aurora B kinase via the conserved C-terminal IN-box, defining the core of the CPC across species.

    Evidence Co-IP from Xenopus extracts, in vitro binding, co-localization, and C. elegans RNAi

    PMID:10996078 PMID:11050385

    Open questions at the time
    • Activation mechanism of Aurora B by INCENP not established
    • Structural basis of IN-box binding unknown
  4. 2001 High

    Showed reciprocal interdependence of INCENP and Aurora B for localization/function and extended the complex to include Survivin and direct microtubule/tubulin binding by INCENP.

    Evidence Drosophila RNAi, yeast two-hybrid, in vitro tubulin/microtubule binding, dicentric chromosome imaging

    PMID:11139336 PMID:11352945 PMID:11516652 PMID:11734997

    Open questions at the time
    • Centromere targeting dependence on cohesion only correlative
    • Stoichiometry of multi-subunit complex unresolved
  5. 2002 High

    Defined the positive-feedback activation mechanism—Aurora B phosphorylates the INCENP C-terminus to potentiate its own kinase activity—and established Survivin-INCENP-Aurora B as a stable ternary complex.

    Evidence In vitro kinase assays with phosphosite mutagenesis (C. elegans), co-IP and gel filtration from Xenopus extracts, yeast bi-orientation genetics

    PMID:11809820 PMID:11853667 PMID:12048181 PMID:12221116

    Open questions at the time
    • Atomic basis of allosteric activation not yet known
    • Quantitative activation thresholds undefined
  6. 2003 High

    Pinpointed the human INCENP TSS phosphosites (Thr893/Ser894/Ser895) whose phosphorylation drives Aurora B activation, and identified Cdc14-mediated INCENP dephosphorylation as the trigger coupling separase activation to anaphase CPC relocalization.

    Evidence Recombinant kinase assays with MS phosphosite mapping and mutagenesis (human); in vitro phosphatase assays and yeast genetics linking separase/Cdc14 to Sli15

    PMID:12925766 PMID:14605209

    Open questions at the time
    • How relocalization silences the checkpoint not yet addressed
    • Phosphatase regulation of human INCENP not directly shown
  7. 2004 High

    Extended INCENP's activating partnership to Aurora C, showing INCENP binds and activates a second Aurora kinase as part of a chromosomal passenger complex.

    Evidence Co-IP, in vitro kinase assays, transfection imaging in mammalian cells

    PMID:15316025

    Open questions at the time
    • Physiological context distinguishing Aurora B vs C unclear
    • Structural basis of AURKC activation not shown
  8. 2005 High

    Provided the structural and regulatory logic of Aurora B activation by INCENP and defined Cdk1 phosphorylation of INCENP as a node controlling Plk1 recruitment and metaphase-to-anaphase timing.

    Evidence X-ray crystallography of Aurora B:IN-box; in vitro kinase assays and siRNA rescue with INCENP Cdk1-site mutants; co-IP

    PMID:15796717 PMID:15866179 PMID:16378098

    Open questions at the time
    • How phosphorylation states are spatially read out in vivo not resolved
    • MKLP1 recruitment mechanism by INCENP not molecularly defined
  9. 2006 High

    Resolved the minimal centromere-targeting module as a Survivin-Borealin-INCENP(N58) subcomplex and added a meiotic cohesion-protection role through MEI-S332 localization.

    Evidence Minimal subcomplex reconstitution with siRNA rescue; Drosophila incenp mutants with in vitro kinase/binding assays

    PMID:16571674 PMID:16824953

    Open questions at the time
    • Centromeric receptor of the subcomplex not identified
    • How targeting and cohesion protection are temporally coupled unclear
  10. 2007 High

    Solved the high-resolution structure of the Survivin-Borealin-INCENP regulatory core, explaining the structural interdependence of CPC subunits for localization.

    Evidence 1.4 Å X-ray crystallography with siRNA rescue mutants and analytical ultracentrifugation; Dictyostelium actin-binding/Kif12 studies

    PMID:17567958 PMID:17956729

    Open questions at the time
    • Connection between core structure and nucleosome engagement not yet known
    • Actin-binding role conservation in vertebrates not established
  11. 2009 High

    Established that graded Aurora B activity levels, set by INCENP C-terminal interactions and substoichiometric catalytic activation, partition distinct mitotic functions and define a kinetic activation mechanism.

    Evidence INCENP activity-mutant depletion/rescue with checkpoint assays; quantitative in vitro kinase kinetics

    PMID:18767990 PMID:19951914

    Open questions at the time
    • Spatial control of activity thresholds in cells not resolved
    • Link between activity level and localization switch incomplete
  12. 2010 High

    Demonstrated that Cdc14-mediated Sli15/INCENP dephosphorylation both relocates the CPC and silences the mitotic checkpoint after cohesin cleavage, establishing a conserved tension-loss bypass mechanism.

    Evidence Budding yeast genetics, phosphatase mutants, and checkpoint assays

    PMID:20619650

    Open questions at the time
    • Direct biochemical targets of dephosphorylation in human cells not mapped
  13. 2011 High

    Showed that Aurora B-dependent INCENP phosphorylation gates CPC-microtubule binding and that Cdk1 and Aurora cooperatively tune microtubule dynamics through INCENP phosphostate.

    Evidence Yeast phosphomutant genetics, live microtubule dynamics imaging, in vitro CPC-microtubule binding

    PMID:21727193

    Open questions at the time
    • Structural basis of the phospho-controlled microtubule switch not defined
  14. 2012 High

    Determined the human Aurora B:INCENP complex structure, revealing a dimeric arrangement and species-specific INCENP binding mode distinct from Xenopus.

    Evidence X-ray crystallography with analytical ultracentrifugation

    PMID:22920039

    Open questions at the time
    • Functional significance of dimerization in vivo not established
  15. 2014 Medium

    Captured a structural conformation in which the INCENP C-terminus occupies the Aurora B substrate site, hinting at a possible trans-inhibitory state.

    Evidence X-ray crystallography of Xenopus Aurora B-INCENP with inhibitor

    PMID:24598913

    Open questions at the time
    • Potential crystal-packing artifact not functionally validated
    • No cellular evidence for trans-inhibition
  16. 2015 High

    Defined the central INCENP region as a single-alpha-helix microtubule-binding 'dog-leash' spacer and identified additional regulatory layers (electrostatic localization switch coupled to H2A dephosphorylation; PRMT1 methylation of Arg887 modulating Aurora B affinity).

    Evidence Biophysical SAH characterization with microtubule binding and rescue cell lines; in vitro multimerization/binding with phospho-H2A manipulation; in vitro methylation with MS and mitotic phenotyping

    PMID:26166576 PMID:26175154 PMID:26460953

    Open questions at the time
    • Quantitative contribution of each affinity in vivo unresolved
    • PRMT1 methylation findings from single lab
  17. 2016 Medium

    Identified LATS1/2 as an alternative INCENP TSS-motif kinase activating Aurora B during multipolar cytokinesis and linked INCENP actin binding to midzone microtubule stabilization feedback.

    Evidence In vitro kinase assays with phosphomutant rescue; actin-binding mutant live imaging with Taxol/Aurora B inhibition

    PMID:26898472 PMID:27512725

    Open questions at the time
    • LATS1/2 role only shown in multipolar context, single lab
    • Generality of actin-binding requirement across cell types unclear
  18. 2017 High

    Showed the SAH domain contributes to chromatin localization and checkpoint function through dual chromatin/microtubule recognition, and that spindle association rather than kinase clustering underlies Aurora B's bi-orientation function.

    Evidence INCENP mutant rescue in Xenopus extracts and mammalian cells; engineered minimal/dimerized CPC in budding yeast with segregation assays

    PMID:28314740 PMID:28314741

    Open questions at the time
    • Precise chromatin receptor for the SAH domain not identified
  19. 2019 High

    Provided the structural mechanism by which TSS-motif phosphorylation fully activates Aurora kinases, identified an alternative kinetochore recruitment route via the COMA complex, and added Plk1 phosphorylation of the INCENP STD-rich motif as a furrow-inducing input.

    Evidence Crystal structures of phosphorylated AURKC:INCENP with biochemical assays; yeast genetics and engineered targeting (COMA); conditional-KO rescue with Plk1 phosphomutants

    PMID:31006569 PMID:31320618 PMID:31601613

    Open questions at the time
    • Whether COMA recruitment operates in vertebrates not shown
    • Crosstalk between multiple INCENP phospho-inputs unresolved
  20. 2021 High

    Established an ATM-Chk2-INCENP-Ser91 axis that imposes the abscission checkpoint by promoting Mklp2-dependent CPC midbody localization, defining a DNA-damage-responsive cytokinesis control through INCENP.

    Evidence siRNA, phosphomimetic/non-phosphorylatable mutant rescue, co-IP, and live abscission imaging

    PMID:33355621

    Open questions at the time
    • How chromatin bridges activate ATM at the midbody not detailed
    • Conformational basis of the dog-leash extension supported only computationally
  21. 2025 Medium

    Revealed a non-catalytic, structural role for the CPC in maintaining centromeric chromatin stability via multipartite engagement of H3Thr3-phosphorylated nucleosomes.

    Evidence CryoEM, AFM, MNase protection, and structure-based mutagenesis with cellular rescue (preprint)

    Open questions at the time
    • Preprint not yet peer-reviewed
    • In vivo consequences of chromatin stabilization for segregation fidelity incompletely defined

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the multiple, often competing INCENP phospho- and methyl-regulatory inputs are integrated in space and time to switch the CPC between its sequential mitotic locations remains unresolved.
  • No unified quantitative model coupling INCENP modifications to localization transitions
  • Endogenous receptor(s) coordinating SAH-mediated chromatin/microtubule handoff not fully defined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 5 GO:0098772 molecular function regulator activity 5 GO:0005198 structural molecule activity 3 GO:0008092 cytoskeletal protein binding 3
Localization
GO:0005694 chromosome 3 GO:0005856 cytoskeleton 3 GO:0000228 nuclear chromosome 2
Pathway
R-HSA-1640170 Cell Cycle 4 R-HSA-4839726 Chromatin organization 2 R-HSA-1474165 Reproduction 1
Partners
AURKBAURKCBIRC5CDCA8HP1KIF20AKIF23PLK1
Complex memberships
Chromosomal passenger complex (CPC)

Evidence

Reading pass · 42 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1987 INCENP (inner centromere protein) was identified as a chromosomal protein that localizes to the inner centromere region between sister chromatids through metaphase, then dissociates from chromosomes at anaphase and transfers to the central spindle and forming contractile ring, ultimately concentrating at the midbody before being discarded at cytokinesis completion. Monoclonal antibody immunofluorescence microscopy of mitotic cells; biochemical fractionation showing INCENP is tightly associated with the chromosome scaffold fraction The Journal of cell biology High 3316246
1998 INCENP has a modular organization: an autonomous N-terminal centromere- and midbody-targeting module within the first 68 amino acids containing two conserved motifs (a 13-aa motif required for centromere targeting/spindle transfer, and an 11-aa motif required for spindle transfer after centromere targeting). INCENP also physically interacts with heterochromatin protein HP1(Hsalpha) via yeast two-hybrid and in vitro binding assays, though this interaction does not appear to mediate centromere targeting. Deletion mutagenesis with GFP-tagged truncation constructs; yeast two-hybrid screen; in vitro binding assays The Journal of cell biology High 9864353
1998 An INCENP truncation mutant (INCENP1-405) that targets to centromeres but lacks the microtubule association region acts as a dominant-negative, displacing endogenous INCENP from centromeres and impairing both prometaphase chromosome alignment and cytokinesis completion, establishing a functional link between centromere association and cytoskeletal events. Expression of truncation mutants in cultured cells; immunofluorescence; dominant-negative phenotype analysis The Journal of cell biology Medium 9490714
2000 INCENP directly binds Aurora B kinase (AIRK2/XAIRK2) in vitro and in vivo; INCENP is required to target Aurora B correctly to centromeres and the central spindle. The conserved C-terminal IN-box domain of INCENP mediates this interaction, and this interaction is evolutionarily conserved (Sli15 is the yeast INCENP ortholog based on the IN-box motif). Co-immunoprecipitation from Xenopus egg extracts; in vitro binding; co-localization by immunofluorescence; yeast genetic analysis Current biology : CB High 10996078
2000 In C. elegans, ICP-1 (INCENP ortholog) and AIR-2 (Aurora B ortholog) form a complex essential for chromosome segregation and cytokinesis; ICP-1 promotes stable localization of ZEN-4 (centralspindlin kinesin) to the central spindle. RNA-mediated interference (RNAi) in C. elegans embryos; in vitro binding; co-immunoprecipitation of mammalian orthologs Current biology : CB High 11050385
2001 In Drosophila, INCENP and Aurora B bind each other in vitro; INCENP is required for Aurora B to localize properly and function as a histone H3 kinase; Aurora B is required for INCENP accumulation at centromeres and transfer to the spindle at anaphase. RNAi of either protein impairs chromosome alignment, causes sister kinetochore disjunction defects, and leads to cytokinesis failure. dsRNA-mediated RNAi in Drosophila cultured cells; in vitro binding; immunofluorescence; biochemical fractionation The Journal of cell biology High 11352945
2001 INCENP localization at the inactive centromere (of stable dicentric chromosomes) correlates strictly with the state of sister chromatid cohesion: loss of cohesion is accompanied by loss of INCENP from the inactive centromere, suggesting INCENP association with centromeres depends on sister chromatid cohesion and not on an active kinetochore. Immunofluorescence on stable dicentric chromosomes with inactive centromeres in human cells Chromosoma Medium 11734997
2001 Survivin directly binds both Aurora B and INCENP by yeast two-hybrid and in vitro pull-down assays; the Survivin-Aurora B interaction resists 3M NaCl. Disruption of INCENP localization in vivo prevents Survivin from concentrating at centromeres or transferring to the anaphase spindle midzone, demonstrating INCENP-dependent targeting of Survivin. Yeast two-hybrid; in vitro pull-down; live-cell Survivin-GFP imaging; co-immunoprecipitation Current biology : CB High 11516652
2001 INCENP binds directly to beta-tubulin (via residues 48–85) and to polymerized microtubules in vitro, and bundles microtubules when expressed in interphase cytoplasm. Targeting of INCENP to the cleavage plane requires dynamic microtubules but not F-actin. Yeast two-hybrid; in vitro binding to purified tubulin/microtubules; treatment with microtubule and actin-depolymerizing drugs; immunofluorescence Experimental cell research High 11139336
2002 In yeast (Ipl1/Aurora B – Sli15/INCENP), the complex promotes chromosome bi-orientation by promoting turnover of kinetochore-spindle pole body connections. In ipl1 mutants, kinetochores remain attached to old SPBs rather than detaching and reattaching to achieve bi-orientation. Yeast genetics; time-lapse microscopy; cell cycle analysis with unreplicated chromosomes; spindle pole body duplication assay Cell High 11853667
2002 C. elegans Aurora B (AIR-2) directly phosphorylates INCENP (ICP-1) at two adjacent serines in the C-terminus; this phosphorylation stimulates AIR-2 kinase activity in a positive feedback loop. Mutation of both serines abolishes the potentiation of AIR-2 activity by ICP-1. In vitro kinase assay with recombinant proteins; site-directed mutagenesis of phosphorylation sites; kinase activity measurements The Journal of biological chemistry High 12048181
2002 Xenopus Survivin, Aurora B, and INCENP form a ternary complex throughout the cell cycle; Survivin and Aurora B bind different domains on INCENP. Survivin binding stimulates Aurora B kinase activity >10-fold (with cell-cycle-dependent phosphorylation required for full activation). The hydrodynamic properties of the complex are cell cycle regulated. Co-immunoprecipitation from Xenopus embryo extracts; kinase activity assays; phosphatase treatment; gel filtration (hydrodynamic analysis) Molecular biology of the cell High 12221116
2002 In Xenopus, the INCENP-Aurora B kinase complex phosphorylates histone H3 and regulates ISWI chromatin remodeling complex association with chromatin; ISWI depletion does not affect chromosome condensation, challenging the model that H3 phosphorylation is required for condensation. Immunodepletion from Xenopus egg extracts; chromatin assembly assays; histone H3 phosphorylation assays Molecular biology of the cell Medium 11809820
2003 Human Aurora B kinase activity is stimulated by INCENP; the C-terminal region (IN-box) of INCENP is sufficient for activation. Aurora B phosphorylates INCENP at Thr893, Ser894, and Ser895 (identified by mass spectrometry); a non-phosphorylatable mutant (TSS893-895AAA) is a poor activator of Aurora B, demonstrating INCENP phosphorylation drives a positive feedback loop for Aurora B activation. Recombinant protein kinase assays; RNA interference (RNAi) depletion; mass spectrometry phosphosite identification; site-directed mutagenesis; immunofluorescence Molecular biology of the cell High 12925766
2003 Yeast Cdc14 phosphatase dephosphorylates Sli15 (yeast INCENP), directing the Ipl1 (Aurora B)-Sli15 complex from kinetochores to spindles at anaphase. Separase activates Cdc14, which is then sufficient to trigger Sli15 dephosphorylation and relocalization, linking chromosome segregation (cohesin cleavage) to spindle midzone assembly. Yeast genetics; in vitro phosphatase assays; live-cell imaging; conditional mutant analysis Science (New York, N.Y.) High 14605209
2004 Aurora C directly binds INCENP in vivo and in vitro; INCENP binding activates Aurora C kinase activity. Aurora C co-expressed with INCENP phosphorylates endogenous histone H3 in mammalian cells. Aurora C forms a complex with Aurora B and INCENP as a chromosomal passenger protein. Co-immunoprecipitation; in vitro kinase assays; transfection and immunofluorescence in mammalian cells The Journal of biological chemistry High 15316025
2005 Crystal structure of Aurora B kinase in complex with the IN-box segment of INCENP (and inhibitor Hesperadin) reveals that INCENP forms a crown around the small lobe of Aurora B, allosterically inducing the active conformation of the T loop. Phosphorylation of two serines in the INCENP C-terminus generates the fully active kinase from an intermediate state where the Aurora B C-terminal segment stabilizes an open conformation of the catalytic cleft. X-ray crystallography; structure-function analysis Molecular cell High 15866179
2005 Cdk1 phosphorylates INCENP at Thr59 and Thr388, regulating Aurora B localization and activity from prophase to metaphase. Phosphorylation at Thr388 is specifically required for recruitment of Plk1 to the kinetochore; T388A mutant delays metaphase-to-anaphase transition. INCENP thus mediates complex formation between Plk1 and Aurora B on kinetochores. In vitro kinase assays; siRNA rescue with INCENP phosphorylation mutants; immunofluorescence; co-immunoprecipitation Nature cell biology High 16378098
2005 INCENP is required for recruiting MKLP1 (mitotic kinesin-like protein 1) to the spindle midzone/midbody; RNAi depletion of INCENP causes abnormal spindle midzone/midbody formation and binucleation. MKLP1 depletion abrogates midbody formation but not midzone assembly or chromosome segregation. RNA interference; immunofluorescence; 3D reconstruction live-cell imaging The Biochemical journal Medium 15796717
2006 A ternary subcomplex of Survivin, Borealin, and the N-terminal 58 amino acids of INCENP is essential and sufficient for centromere targeting of the chromosomal passenger complex; Aurora B kinase is not required for centromere localization of this subcomplex. CPC centromere targeting does not require CENP-A or hMis12. In vitro binding assays; siRNA rescue with structure-based mutants; co-immunoprecipitation; immunofluorescence; stable cell line generation Molecular biology of the cell High 16571674
2006 INCENP and Aurora B promote meiotic sister chromatid cohesion through localization of the cohesion protector protein MEI-S332; INCENP binds MEI-S332 directly, and MEI-S332 is an in vitro substrate of Aurora B kinase. A MEI-S332 mutant poorly phosphorylated by Aurora B is defective in centromere localization. Drosophila incenp mutant analysis; in vitro kinase assays; co-immunoprecipitation/binding assays; immunofluorescence Developmental cell High 16824953
2007 Crystal structure at 1.4 Å resolution of the Survivin-Borealin-INCENP regulatory core of the CPC reveals that Borealin and INCENP associate with the helical domain of Survivin to form a tight three-helical bundle. siRNA rescue with structure-based mutants shows that intertwined structural interactions of core components create functional interdependence for central spindle and midbody localization. X-ray crystallography (1.4 Å); siRNA rescue with structure-based mutants; analytical ultracentrifugation Cell High 17956729
2007 In Dictyostelium, INCENP localization to the cleavage furrow cortex requires the kinesin-6-related protein Kif12 and involves direct binding of the INCENP N-terminus to the actin cytoskeleton. Kif12 is required for INCENP transfer from the central spindle to the furrow cortex, but not for redistribution from centromeres to the central spindle. Kif12 knockout analysis; domain truncation mutants; in vitro actin binding assays; immunofluorescence Molecular biology of the cell Medium 17567958
2009 INCENP C-terminus interactions with Aurora B modulate the level of kinase activity in vivo, which in turn regulates CPC localization and distinct mitotic functions. Low kinase activity is sufficient for spindle checkpoint response when microtubules are absent, intermediate activity supports robust taxol checkpoint response, but CPC transfer from chromosomes to anaphase spindle midzone requires significantly higher activity levels. INCENP conditional depletion/rescue with activity mutants; kinase activity measurements; live-cell imaging; spindle checkpoint assays The Journal of cell biology High 19951914
2009 INCENP plays a catalytic role in Aurora B (AurB) autophosphorylation at Thr232 (activation loop); substoichiometric INCENP concentrations are sufficient for AurB autophosphorylation. The AurB/INCENP-catalysed phosphorylation of peptide substrate proceeds through a rapid equilibrium random Bi Bi kinetic mechanism. In vitro kinase assays with varying INCENP concentrations; kinetics analysis; mass spectrometry The Biochemical journal High 18767990
2010 Cdc14 phosphatase dephosphorylates Sli15 (INCENP) at anaphase onset, relocating the complex from centromeres to the central spindle and preventing re-engagement of the mitotic checkpoint after cohesin cleavage (which releases tension). This establishes an evolutionarily conserved mechanism coupling separase/Cdc14 activation to mitotic checkpoint silencing. Budding yeast genetics; phosphatase mutant analysis; live-cell imaging; spindle assembly checkpoint assays Current biology : CB High 20619650
2011 Ipl1 (Aurora B)-dependent phosphorylation of Sli15 (INCENP) prevents CPC binding to the preanaphase spindle and central spindle until late anaphase; decreased Ipl1-dependent Sli15 phosphorylation drives direct CPC binding to microtubules, influencing microtubule dynamics. Cdk1 and Ipl1/Aurora cooperatively modulate microtubule dynamics through Sli15 phosphorylation. Yeast genetics; phosphomutant analysis; microtubule dynamics measurements (live imaging); in vitro CPC-microtubule binding assays The Journal of cell biology High 21727193
2012 Crystal structure of human Aurora B kinase domain in complex with human INCENP C-terminal region and inhibitor VX-680 reveals a dimeric arrangement of the Aurora B:INCENP complex confirmed by analytical ultracentrifugation; INCENP binding mode differs significantly from the Xenopus Aurora B:INCENP complex. X-ray crystallography; analytical ultracentrifugation Journal of medicinal chemistry High 22920039
2014 Crystal structure of Xenopus Aurora B-INCENP complex with barasertib inhibitor reveals a crystal-packing contact where the INCENP C-terminus occupies the substrate-binding region of Aurora B, resembling a trans-inhibitory mechanism analogous to protein kinase A inhibition. X-ray crystallography Acta crystallographica. Section F, Structural biology communications Medium 24598913
2015 The central region of chicken INCENP (213 residues) is not a coiled coil but a ~32-nm-long single alpha-helix (SAH) domain; the N-terminal half of this SAH domain directly binds microtubules in vitro. The SAH domain acts as a flexible spacer ('dog leash') allowing Aurora B to reach outer kinetochore substrates while the CPC is anchored at the inner centromere. Biophysical analysis (CD spectroscopy, analytical ultracentrifugation); in vitro microtubule binding assays; mutagenesis; INCENP-knockout/rescue cell lines The Journal of biological chemistry High 26175154
2015 PRMT1 arginine methyltransferase methylates INCENP at Arg887 in the Aurora B-binding IN-box region both in vitro and in vivo. R887-methylated INCENP shows lower binding affinity to Aurora B; PRMT1 knockdown or expression of methylation-inactive INCENP attenuates Aurora B activity and causes abnormal chromosome alignment/segregation. In vitro methylation assays; mass spectrometry; co-immunoprecipitation; kinase activity assays; chromosome segregation analysis Oncotarget Medium 26460953
2015 The putative coiled-coil domain within INCENP drives midzone localization of Aurora B via a direct electrostatic interaction with microtubules. The CPC multimerizes via INCENP's centromere-targeting (CEN box) domain, which increases microtubule-binding affinity. At anaphase onset, when H2AT120 is dephosphorylated, the microtubule-binding affinity outcompetes centromere affinity, switching CPC from centromere to microtubule localization. In vitro microtubule binding assays; multimerization assays; cell-based rescue experiments with INCENP mutants; phospho-H2A manipulation Cell reports Medium 26166576
2016 LATS1/2 kinases phosphorylate INCENP at Ser894 (within the TSS motif); this LATS-mediated phosphorylation is necessary and sufficient for Aurora B activation during cytokinesis in cells undergoing multipolar division. In vitro kinase assays; phosphomutant rescue experiments; Aurora B activity assays in cells; RNA interference Heliyon Medium 27512725
2016 INCENP's actin-binding activity is important for cytokinesis and for midzone microtubule stabilization following furrow ingression; midzone microtubule stabilization depends on actomyosin contraction and Aurora B kinase activity, establishing a feedback between furrow ingression and microtubule dynamics mediated by the CPC. INCENP actin-binding mutant expression; live-cell imaging; Taxol rescue experiments; Aurora B inhibition Current biology : CB Medium 26898472
2017 In addition to Survivin and Borealin, the SAH domain of INCENP supports CPC localization to chromatin and mitotic checkpoint function. INCENP SAH domain microtubule binding is negatively regulated by CDK-mediated phosphorylation of flanking segments. Dual recognition of chromatin and microtubules by INCENP is required for robust mitotic arrest. INCENP mutant rescue in Xenopus egg extracts and mammalian cells; microtubule binding assays; phosphomutant analysis; spindle checkpoint assays The Journal of cell biology High 28314740
2017 In budding yeast, spindle association via the INCENP (Sli15) microtubule-binding domain is important for Aurora B (Ipl1) function in chromosome biorientation. Artificial dimerization of a minimal CPC (dimerized last-third of Sli15 + Ipl1) suppresses biorientation defects by promoting spindle association rather than by kinase clustering; a putative helical domain in Sli15 is required even when dimerized. Engineered minimal CPC with artificial dimerization (budding yeast); in vivo chromosome segregation assays; kinase activity measurements The Journal of cell biology Medium 28314741
2019 The COMA inner kinetochore sub-complex physically interacts with Sli15 (INCENP) and recruits Ipl1-Sli15 (Aurora B-INCENP) to the inner kinetochore independently of Bir1 (survivin). Localization of Ipl1-Sli15 at centromeres or inner kinetochores is required for chromosome bi-orientation, established by engineered recruitment when both Bir1 and COMA are defective. Yeast genetics; co-immunoprecipitation; engineered kinetochore targeting; chromosome segregation assays Current biology : CB High 31006569
2019 Crystal structures of the fully active AURKC:INCENP complex (with phosphorylated INCENP TSS motif) reveal that TSS motif phosphorylation stabilizes the kinase activation loop of AURKC and alters the substrate-binding surface, explaining the mechanism of synergistic Aurora C/B activation by INCENP phosphorylation. VX-680 inhibitor disrupts phosphorylated INCENP TSS motif binding. X-ray crystallography; biochemical kinase assays; native MS; thermal stability assays Nature communications High 31320618
2019 Phosphomimetic mutations of the INCENP STD-rich motif (phosphorylated by Plk1 in vitro and during mitosis in vivo) induce ectopic furrows and contractile ring formation in a Plk1- and ROCK1-dependent manner, independent of cell cycle and microtubule status. Non-phosphorylatable mutants cause chromosome congression failure and cytokinesis failure. INCENP conditional-knockout cell line; phosphomimetic and non-phosphorylatable mutant rescue; in vitro Plk1 kinase assay; live-cell imaging Journal of cell science Medium 31601613
2021 An ATM-Chk2-INCENP pathway imposes the abscission checkpoint in response to chromatin bridges. ATM activates Chk2 at late midbodies; Chk2 phosphorylates human INCENP at Ser91, promoting INCENP binding to Mklp2 kinesin, which associates with Cep55 to localize the CPC to the midbody center and delay abscission. Nonphosphorylatable INCENP-Ser91A impairs CPC midbody localization and accelerates abscission; phosphomimetic INCENP-Ser91D rescues abscission delay in Chk2- or ATM-deficient cells. siRNA knockdown; phosphomimetic/non-phosphorylatable mutant rescue; co-immunoprecipitation; in vivo phosphorylation analysis; live-cell abscission imaging The Journal of cell biology High 33355621
2021 Phosphorylation of INCENP's intrinsically disordered region (IDR) expands its conformation by increasing net charge, shifting the IDR from globular collapsed states to extended coil conformations. This phosphorylation-regulated length change modulates how Aurora B reaches its kinetochore targets, supporting the 'dog-leash' model. All-atom and coarse-grain molecular dynamics simulations of INCENP IDR with varying phosphorylation levels Journal of molecular biology Low 34883116
2025 CryoEM structure of the CPC (Borealin-Survivin-INCENP) bound to H3Thr3-phosphorylated nucleosomes reveals multipartite interactions: N-terminus of Borealin and Survivin BIR domain act as pivot and flexible tethering points for CPC engagement at the nucleosome acidic patch and DNA entry-exit site. Perturbation of the CPC-nucleosome interaction compromises MNase protection in vitro and dynamic centromere association in cells, revealing a non-catalytic role for CPC in maintaining centromeric chromatin stability. CryoEM structure determination; atomic force microscopy; MNase protection assays; structure-based mutagenesis with cellular rescue bioRxivpreprint Medium

Source papers

Stage 0 corpus · 80 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 Evidence that the Ipl1-Sli15 (Aurora kinase-INCENP) complex promotes chromosome bi-orientation by altering kinetochore-spindle pole connections. Cell 603 11853667
2003 Exploring the functional interactions between Aurora B, INCENP, and survivin in mitosis. Molecular biology of the cell 453 12925766
2000 Survivin and the inner centromere protein INCENP show similar cell-cycle localization and gene knockout phenotype. Current biology : CB 441 11084331
2001 Essential roles of Drosophila inner centromere protein (INCENP) and aurora B in histone H3 phosphorylation, metaphase chromosome alignment, kinetochore disjunction, and chromosome segregation. The Journal of cell biology 399 11352945
1987 The inner centromere protein (INCENP) antigens: movement from inner centromere to midbody during mitosis. The Journal of cell biology 354 3316246
2005 Mechanism of Aurora B activation by INCENP and inhibition by hesperadin. Molecular cell 337 15866179
2007 Structure of a Survivin-Borealin-INCENP core complex reveals how chromosomal passengers travel together. Cell 287 17956729
2000 INCENP binds the Aurora-related kinase AIRK2 and is required to target it to chromosomes, the central spindle and cleavage furrow. Current biology : CB 273 10996078
2002 Aurora B kinase exists in a complex with survivin and INCENP and its kinase activity is stimulated by survivin binding and phosphorylation. Molecular biology of the cell 271 12221116
2000 Incenp and an aurora-like kinase form a complex essential for chromosome segregation and efficient completion of cytokinesis. Current biology : CB 267 11050385
2001 INCENP is required for proper targeting of Survivin to the centromeres and the anaphase spindle during mitosis. Current biology : CB 239 11516652
2002 Phosphorylation of the carboxyl terminus of inner centromere protein (INCENP) by the Aurora B Kinase stimulates Aurora B kinase activity. The Journal of biological chemistry 228 12048181
2003 Separase regulates INCENP-Aurora B anaphase spindle function through Cdc14. Science (New York, N.Y.) 224 14605209
1998 INCENP centromere and spindle targeting: identification of essential conserved motifs and involvement of heterochromatin protein HP1. The Journal of cell biology 184 9864353
2005 Complex formation of Plk1 and INCENP required for metaphase-anaphase transition. Nature cell biology 156 16378098
2006 Centromere targeting of the chromosomal passenger complex requires a ternary subcomplex of Borealin, Survivin, and the N-terminal domain of INCENP. Molecular biology of the cell 145 16571674
2001 Functional cooperation of Dam1, Ipl1, and the inner centromere protein (INCENP)-related protein Sli15 during chromosome segregation. The Journal of cell biology 144 11724818
1998 A dominant mutant of inner centromere protein (INCENP), a chromosomal protein, disrupts prometaphase congression and cytokinesis. The Journal of cell biology 135 9490714
2004 Direct association with inner centromere protein (INCENP) activates the novel chromosomal passenger protein, Aurora-C. The Journal of biological chemistry 128 15316025
2002 ISWI remodeling complexes in Xenopus egg extracts: identification as major chromosomal components that are regulated by INCENP-aurora B. Molecular biology of the cell 118 11809820
2006 INCENP and Aurora B promote meiotic sister chromatid cohesion through localization of the Shugoshin MEI-S332 in Drosophila. Developmental cell 111 16824953
2003 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. The Journal of biological chemistry 111 14610074
2001 Human INCENP colocalizes with the Aurora-B/AIRK2 kinase on chromosomes and is overexpressed in tumour cells. Chromosoma 107 11453556
2012 Crystal structure of human aurora B in complex with INCENP and VX-680. Journal of medicinal chemistry 85 22920039
1999 Defective chromosome segregation, microtubule bundling and nuclear bridging in inner centromere protein gene (Incenp)-disrupted mice. Human molecular genetics 85 10369859
2003 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. The Journal of cell biology 83 12707312
2005 Recruitment of MKLP1 to the spindle midzone/midbody by INCENP is essential for midbody formation and completion of cytokinesis in human cells. The Biochemical journal 82 15796717
2010 Sli15(INCENP) dephosphorylation prevents mitotic checkpoint reengagement due to loss of tension at anaphase onset. Current biology : CB 71 20619650
1999 Cleavage furrows formed between centrosomes lacking an intervening spindle and chromosomes contain microtubule bundles, INCENP, and CHO1 but not CENP-E. Molecular biology of the cell 71 9950678
2009 INCENP-aurora B interactions modulate kinase activity and chromosome passenger complex localization. The Journal of cell biology 68 19951914
2001 INCENP binds directly to tubulin and requires dynamic microtubules to target to the cleavage furrow. Experimental cell research 68 11139336
2003 Dynamic relocalization of the chromosomal passenger complex proteins inner centromere protein (INCENP) and aurora-B kinase during male mouse meiosis. Journal of cell science 67 12584241
2015 The Inner Centromere Protein (INCENP) Coil Is a Single α-Helix (SAH) Domain That Binds Directly to Microtubules and Is Important for Chromosome Passenger Complex (CPC) Localization and Function in Mitosis. The Journal of biological chemistry 59 26175154
2008 Dual roles of Incenp crucial to the assembly of the acentrosomal metaphase spindle in female meiosis. Development (Cambridge, England) 55 18755775
2019 Aurora B-INCENP Localization at Centromeres/Inner Kinetochores Is Required for Chromosome Bi-orientation in Budding Yeast. Current biology : CB 54 31006569
1998 Colocalization of TD-60 and INCENP throughout G2 and mitosis: evidence for their possible interaction in signalling cytokinesis. Chromosoma 47 9914378
2015 Inter-domain Cooperation in INCENP Promotes Aurora B Relocation from Centromeres to Microtubules. Cell reports 45 26166576
2005 Overexpression of an Aurora-C kinase-deficient mutant disrupts the Aurora-B/INCENP complex and induces polyploidy. Journal of biomedical science 42 15917996
2011 Ipl1/Aurora-dependent phosphorylation of Sli15/INCENP regulates CPC-spindle interaction to ensure proper microtubule dynamics. The Journal of cell biology 39 21727193
2005 Suppressors of Bir1p (Survivin) identify roles for the chromosomal passenger protein Pic1p (INCENP) and the replication initiation factor Psf2p in chromosome segregation. Molecular and cellular biology 38 16199877
2013 v-Src causes delocalization of Mklp1, Aurora B, and INCENP from the spindle midzone during cytokinesis failure. Experimental cell research 37 23562843
2017 Dual recognition of chromatin and microtubules by INCENP is important for mitotic progression. The Journal of cell biology 35 28314740
2020 lncRNA MIAT promotes esophageal squamous cell carcinoma progression by regulating miR-1301-3p/INCENP axis and interacting with SOX2. Journal of cellular physiology 33 31943174
2019 Structural mechanism of synergistic activation of Aurora kinase B/C by phosphorylated INCENP. Nature communications 33 31320618
2014 Structure of Aurora B-INCENP in complex with barasertib reveals a potential transinhibitory mechanism. Acta crystallographica. Section F, Structural biology communications 33 24598913
2015 PRMT1 promotes mitosis of cancer cells through arginine methylation of INCENP. Oncotarget 31 26460953
2019 Targeting the Chromosomal Passenger Complex Subunit INCENP Induces Polyploidization, Apoptosis, and Senescence in Neuroblastoma. Cancer research 25 31416840
2010 Centromere localization of INCENP-Aurora B is sufficient to support spindle checkpoint function. Cell cycle (Georgetown, Tex.) 25 20372054
2007 The localization of inner centromeric protein (INCENP) at the cleavage furrow is dependent on Kif12 and involves interactions of the N terminus of INCENP with the actin cytoskeleton. Molecular biology of the cell 24 17567958
2021 An ATM-Chk2-INCENP pathway activates the abscission checkpoint. The Journal of cell biology 23 33355621
2017 An engineered minimal chromosomal passenger complex reveals a role for INCENP/Sli15 spindle association in chromosome biorientation. The Journal of cell biology 23 28314741
2008 Perturbation of Incenp function impedes anaphase chromatid movements and chromosomal passenger protein flux at centromeres. Chromosoma 23 18784935
2014 Targeting the INCENP IN-box-Aurora B interaction to inhibit CPC activity in vivo. Open biology 22 25392451
2016 The Timing of Midzone Stabilization during Cytokinesis Depends on Myosin II Activity and an Interaction between INCENP and Actin. Current biology : CB 21 26898472
2016 Aurora-C Interactions with Survivin and INCENP Reveal Shared and Distinct Features Compared with Aurora-B Chromosome Passenger Protein Complex. PloS one 21 27332895
2006 EVI5 protein associates with the INCENP-aurora B kinase-survivin chromosomal passenger complex and is involved in the completion of cytokinesis. Experimental cell research 19 16764853
2001 INCENP loss from an inactive centromere correlates with the loss of sister chromatid cohesion. Chromosoma 18 11734997
2004 Recapitulation of the Roberts syndrome cellular phenotype by inhibition of INCENP, ZWINT-1 and ZW10 genes. Gene 17 15094189
2009 The catalytic role of INCENP in Aurora B activation and the kinetic mechanism of Aurora B/INCENP. The Biochemical journal 16 18767990
2015 Inherited variants in the inner centromere protein (INCENP) gene of the chromosomal passenger complex contribute to the susceptibility of ER-negative breast cancer. Carcinogenesis 15 25586992
2006 Drosophila Incenp is required for cytokinesis and asymmetric cell division during development of the nervous system. Journal of cell science 14 16507586
2016 Functional SNPs of INCENP Affect Semen Quality by Alternative Splicing Mode and Binding Affinity with the Target Bta-miR-378 in Chinese Holstein Bulls. PloS one 13 27669152
2021 Phosphorylation tunes elongation propensity and cohesiveness of INCENP's intrinsically disordered region. Journal of molecular biology 12 34883116
2009 The COMA complex is required for Sli15/INCENP-mediated correction of defective kinetochore attachments. Cell cycle (Georgetown, Tex.) 11 19597337
2007 Autoantibodies against the chromosomal passenger protein INCENP found in a patient with Graham Little-Piccardi-Lassueur syndrome. Journal of autoimmune diseases 10 17222351
2016 Large tumor suppressors 1 and 2 regulate Aurora-B through phosphorylation of INCENP to ensure completion of cytokinesis. Heliyon 9 27512725
2012 Translation of incenp during oocyte maturation is required for embryonic development in Xenopus laevis. Biology of reproduction 9 22378760
2008 Regulation of Sli15/INCENP, kinetochore, and Cdc14 phosphatase functions by the ribosome biogenesis protein Utp7. The Journal of cell biology 8 18794331
2019 Switching of INCENP paralogs controls transitions in mitotic chromosomal passenger complex functions. Cell cycle (Georgetown, Tex.) 7 31306061
2008 INCENP (inner centromere protein) is overexpressed in high grade non-Hodgkin B-cell lymphomas. Pathology oncology research : POR 7 18752045
1998 Genetic mapping of mouse centromere protein (Incenp and Cenpe) genes. Cytogenetics and cell genetics 5 9763662
2022 Computational study of the potential impact of AURKC missense SNPs on AURKC-INCENP interaction and their correlation to macrozoospermia. Journal of biomolecular structure & dynamics 4 36326488
2021 An ATM-CHK2-INCENP pathway prevents chromatin breakage by regulating the abscission checkpoint. Molecular & cellular oncology 4 33860082
2016 A small molecule identified through an in silico screen inhibits Aurora B-INCENP interaction. Chemical biology & drug design 4 27390292
2019 Cell cycle-independent furrowing triggered by phosphomimetic mutations of the INCENP STD motif requires Plk1. Journal of cell science 2 31601613
2024 Robust approach for production of the human oncology target Aurora kinase B in complex with its binding partner INCENP. Biochimie 1 39424257
2016 [Functional haplotypes of INCENP affect promoter activity and bovine semen quality]. Yi chuan = Hereditas 1 26787524
2026 INCENP and CDCA8 predict neoadjuvant chemotherapy response and outcomes in esophageal squamous cell carcinoma. Nature communications 0 41565643
2025 Aurora B and INCENP co-overexpression severely disrupts mitosis and distinctly modifies the global transcriptional landscape. iScience 0 40530423
2013 Structural basis for binding of aurora-AG198N- INCENP complex: MD simulations and free energy calculations. Protein and peptide letters 0 23848594

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