Affinage

INCENP

Inner centromere protein · UniProt Q9NQS7

Length
918 aa
Mass
105.4 kDa
Annotated
2026-04-28
81 papers in source corpus 46 papers cited in narrative 46 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

INCENP is the central scaffold of the chromosomal passenger complex (CPC), organizing Aurora B kinase activation, centromere targeting, spindle midzone transfer, and cytokinesis signaling throughout cell division. Its N-terminal domain forms a three-helical bundle with Survivin and Borealin that is necessary and sufficient for centromere targeting via phospho-H3T3 nucleosome recognition, while its C-terminal IN-box allosterically induces the active conformation of Aurora B's T-loop and participates in a positive-feedback phosphorylation loop at the TSS motif (Thr893/Ser894/Ser895) that fully activates the kinase (PMID:15866179, PMID:12925766, PMID:17956729). The central single α-helix (SAH) domain binds microtubules directly, driving anaphase midzone relocalization and acting as a flexible tether that extends Aurora B's reach to outer kinetochore substrates; this microtubule binding is negatively regulated by CDK1 phosphorylation, confining the CPC to centromeres before anaphase, while Cdc14-mediated dephosphorylation at anaphase onset triggers spindle transfer (PMID:26175154, PMID:14605209, PMID:21727193). Multiple regulatory inputs converge on INCENP — CDK1 phosphorylation recruits Plk1 to kinetochores, Plk1 phosphorylation of the STD motif promotes cytokinesis, PRMT1 methylation at Arg887 attenuates Aurora B binding, LATS1/2 phosphorylation at Ser894 activates Aurora B during multipolar division, and Chk2 phosphorylation at Ser91 enforces the abscission checkpoint by promoting INCENP–Mklp2 interaction at midbodies (PMID:16378098, PMID:31601613, PMID:26460953, PMID:27512725, PMID:33355621).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 1987 High

    The discovery that INCENP localizes to the inner centromere at metaphase and then transfers to the central spindle and midbody defined a new class of 'chromosomal passenger' proteins and predicted roles in sister chromatid pairing and cytokinesis.

    Evidence Monoclonal antibody immunofluorescence and chromosome scaffold fractionation in mammalian cells

    PMID:3316246

    Open questions at the time
    • No molecular function assigned
    • Mechanism of localization unknown
    • Binding partners unidentified
  2. 1998 High

    Mapping of the N-terminal 68 amino acids as an autonomous centromere- and midbody-targeting module, and demonstration that a dominant-negative truncation mutant disrupts chromosome alignment and cytokinesis, established that centromere association is a prerequisite for subsequent spindle targeting.

    Evidence GFP-fusion truncation mutagenesis, dominant-negative overexpression, immunofluorescence in human cells

    PMID:9490714 PMID:9864353

    Open questions at the time
    • Centromere receptor unknown
    • No enzymatic activity identified for INCENP itself
  3. 2000 High

    Identification of a direct physical interaction between INCENP and Aurora B kinase (conserved from yeast to vertebrates via the C-terminal IN-box) revealed that INCENP functions as the targeting and regulatory scaffold for Aurora B, explaining the shared phenotypes of their loss-of-function.

    Evidence Co-immunoprecipitation from Xenopus extracts, in vitro binding, RNAi in C. elegans, conserved IN-box domain identification

    PMID:10996078 PMID:11050385

    Open questions at the time
    • Mechanism of kinase activation unknown
    • Whether INCENP activates or merely localizes Aurora B unresolved
  4. 2001 High

    Demonstration that Survivin binds both Aurora B and INCENP, that INCENP binds microtubules via a tubulin-binding domain, and that yeast INCENP (Sli15) stimulates Ipl1 kinase activity expanded the CPC model from a binary Aurora B–INCENP pair to a multi-subunit complex with scaffolding, targeting, and kinase-stimulatory functions.

    Evidence Yeast two-hybrid, in vitro pull-down, in vitro kinase assay, microtubule binding/bundling assay, RNAi (Drosophila, yeast)

    PMID:11139336 PMID:11352945 PMID:11516652 PMID:11724818

    Open questions at the time
    • Borealin not yet identified
    • Structural basis of kinase activation unknown
    • Quantitative stimulation mechanism unresolved
  5. 2002 High

    Identification of the INCENP TSS motif (Thr893/Ser894/Ser895) as an Aurora B phosphorylation site required for full kinase activation established a positive-feedback loop and the CPC's role in promoting chromosome bi-orientation by destabilizing incorrect kinetochore–microtubule attachments.

    Evidence In vitro kinase assay with mutagenesis and mass spectrometry in human and C. elegans systems; yeast genetic epistasis with unreplicated chromosomes

    PMID:11853667 PMID:12048181 PMID:12925766

    Open questions at the time
    • Structural mechanism of feedback unknown
    • Upstream phosphatases not identified in metazoans
  6. 2003 High

    Discovery that Cdc14 phosphatase dephosphorylates INCENP/Sli15 at anaphase onset to trigger centromere-to-spindle transfer identified the molecular switch governing CPC relocalization, and recognition of Borealin as a fourth CPC subunit completed the complex's composition.

    Evidence In vitro dephosphorylation and genetic epistasis in yeast (Cdc14/separase); in vitro reconstitution and RNAi in C. elegans (Borealin/CSC-1)

    PMID:12707312 PMID:14605209

    Open questions at the time
    • Metazoan Cdc14 equivalence debated
    • How Borealin contacts chromatin unclear
  7. 2005 High

    The crystal structure of Aurora B bound to the INCENP IN-box revealed how INCENP allosterically induces the active T-loop conformation, and CDK1 phosphorylation of INCENP Thr388 was shown to recruit Plk1 to kinetochores, uncovering cross-talk between major mitotic kinases converging on INCENP.

    Evidence X-ray crystallography (Xenopus Aurora B–IN-box–Hesperadin), in vitro kinase assay, mutagenesis and RNAi rescue in human cells

    PMID:15866179 PMID:16378098

    Open questions at the time
    • Full-length INCENP structure absent
    • Plk1 recruitment mechanism downstream of Thr388 not structurally resolved
  8. 2006 High

    Reconstitution of the Survivin–Borealin–INCENP(1-58) ternary subcomplex as the minimal centromere-targeting module, and its high-resolution crystal structure revealing a three-helical bundle, established the structural basis for CPC centromere recognition independently of Aurora B.

    Evidence In vitro reconstitution, siRNA rescue with structure-based mutants, X-ray crystallography (1.4 Å)

    PMID:16571674 PMID:17956729

    Open questions at the time
    • Nucleosome-binding interface not resolved
    • Role of histone marks in targeting not structurally defined
  9. 2011 High

    Demonstration that Ipl1/Aurora B-dependent phosphorylation of INCENP/Sli15 prevents premature CPC binding to preanaphase spindle microtubules established a dual CDK1–Aurora B phosphoregulatory switch controlling the timing of CPC–microtubule association.

    Evidence Phosphorylation site mutagenesis, in vitro microtubule binding, yeast genetics, live-cell imaging

    PMID:21727193

    Open questions at the time
    • Precise phosphorylation thresholds for metazoan CPC transfer unclear
    • Direct structural visualization of phospho-regulated binding absent
  10. 2015 High

    Identification of the central INCENP domain as a single α-helix (SAH) rather than a coiled coil, with direct microtubule-binding capacity and mechanical extensibility to ~80 nm, provided a biophysical basis for the 'dog-leash' model explaining how centromere-anchored Aurora B reaches outer kinetochore substrates; concurrently, PRMT1 methylation at Arg887 was shown to modulate Aurora B binding affinity.

    Evidence Biophysical SAH characterization, in vitro microtubule binding, mutagenesis, in vitro methylation assay, mass spectrometry, siRNA

    PMID:26166576 PMID:26175154 PMID:26460953

    Open questions at the time
    • In vivo force measurements on SAH extension not performed
    • Methylation dynamics during mitosis not characterized
  11. 2019 High

    Discovery that Plk1 phosphorylates the INCENP STD motif to promote cytokinesis independently of microtubules, that the COMA inner kinetochore complex recruits INCENP–Aurora B independently of Survivin in yeast, and that crystal structures of fully active Aurora C–phospho-INCENP revealed how TSS phosphorylation reshapes the substrate-binding surface, collectively refined understanding of how INCENP integrates multiple kinase inputs and centromere docking modes.

    Evidence In vitro kinase assay and conditional-KO rescue (Plk1–STD); Co-IP and engineered recruitment in yeast (COMA); X-ray crystallography and native MS (Aurora C–INCENP)

    PMID:31006569 PMID:31320618 PMID:31601613

    Open questions at the time
    • Whether COMA-based recruitment is conserved in metazoans unknown
    • STD motif downstream effectors beyond ROCK1 not mapped
  12. 2021 High

    An ATM–Chk2–INCENP(Ser91) phosphorylation cascade was identified as the molecular basis of the abscission checkpoint, linking DNA damage signaling to CPC localization at midbodies via Mklp2–Cep55, thus extending INCENP's regulatory scope beyond chromosome segregation into genome-integrity-dependent abscission control.

    Evidence Kinase inhibition, phosphomimetic/nonphosphorylatable INCENP mutants, Co-IP, live-cell abscission timing assays

    PMID:33355621

    Open questions at the time
    • Whether Chk2–INCENP interaction is direct not demonstrated by structural data
    • Contribution of Aurora B kinase activity vs. scaffolding at midbody not separated

Open questions

Synthesis pass · forward-looking unresolved questions
  • A full structural model of the intact four-subunit CPC bound to nucleosomes and microtubules simultaneously remains unresolved, as does the precise mechanism by which graded INCENP phosphorylation tunes the conformational dynamics of the SAH domain in vivo to control Aurora B substrate access.
  • No full-length CPC structure available
  • In vivo force/extension measurements of SAH absent
  • Metazoan phosphatase(s) responsible for INCENP dephosphorylation at anaphase not definitively identified

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008092 cytoskeletal protein binding 5 GO:0098772 molecular function regulator activity 5 GO:0060090 molecular adaptor activity 4
Localization
GO:0005856 cytoskeleton 5 GO:0005694 chromosome 4
Pathway
R-HSA-1640170 Cell Cycle 7 R-HSA-4839726 Chromatin organization 2
Partners
AURKBAURKCBIRC5CDCA8CHEK2MKLP1PLK1PRMT1
Complex memberships
Chromosomal Passenger Complex (CPC)

Evidence

Reading pass · 46 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1987 INCENP (INCENPs, two polypeptides of 155 and 135 kD) localizes to the inner centromere region between sister chromatids through metaphase, then dissociates from chromosomes at anaphase, transferring to the central spindle and then to the midbody, suggesting roles in sister chromatid pairing, cleavage plane stabilization, and cytokinesis. Monoclonal antibody immunofluorescence microscopy; chromosome scaffold fractionation The Journal of cell biology High 3316246
1998 The N-terminal 68 amino acids of INCENP constitute an autonomous centromere- and midbody-targeting module containing two conserved motifs: a 13-amino acid motif required for centromere targeting and spindle transfer, and an 11-amino acid 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, though this interaction is not required for centromere targeting. Truncation mutagenesis, transfection of GFP fusions, yeast two-hybrid screen, in vitro binding assay 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, disrupting prometaphase chromosome alignment and cytokinesis completion by displacing endogenous INCENP from centromeres, demonstrating that centromere association is required for proper spindle subdomain targeting at anaphase. Truncation mutant overexpression, immunofluorescence microscopy The Journal of cell biology High 9490714
2000 INCENP binds directly to Aurora B kinase (AIRK2) in vitro and is required to target Aurora B to centromeres and the central spindle in human cells. This interaction is evolutionarily conserved: the yeast INCENP ortholog Sli15 interacts with yeast Aurora kinase Ipl1 via a conserved C-terminal 'IN box' domain. Co-immunoprecipitation from Xenopus egg extracts, in vitro binding assay, immunofluorescence colocalization, identification of conserved IN box domain Current biology : CB High 10996078
2000 C. elegans INCENP ortholog ICP-1 binds C. elegans Aurora B kinase AIR-2 in vitro; depletion of ICP-1 or AIR-2 by RNAi causes identical defects in chromosome segregation and cytokinesis; ICP-1 promotes stable localization of the centralspindlin component ZEN-4 to the central spindle. In vitro binding, RNAi depletion with phenotypic analysis, immunofluorescence Current biology : CB High 11050385
2001 Drosophila INCENP (DmINCENP) and Aurora B (DmAurora B) bind each other in vitro; DmINCENP is required for DmAurora B to localize properly in mitosis and function as a histone H3 kinase; DmAurora B is required for DmINCENP accumulation at centromeres and transfer to the spindle at anaphase. RNAi of either protein inhibits metaphase chromosome alignment, causes defects in sister kinetochore disjunction, and frequently causes cytokinesis failure. In vitro binding, dsRNA-mediated RNAi, immunofluorescence, histone H3 kinase assay The Journal of cell biology High 11352945
2001 Survivin binds directly to both Aurora B and INCENP in yeast two-hybrid and in vitro pull-down assays; disruption of INCENP localization causes Survivin to remain on chromosomes and fail to concentrate at centromeres or transfer to the anaphase spindle midzone, demonstrating functional interdependence for localization. Yeast two-hybrid, in vitro pull-down, GFP live-cell imaging, immunofluorescence with INCENP function disruption Current biology : CB High 11516652
2001 INCENP and Aurora B colocalize on human metaphase chromosomes, consistent with their biochemical complex; INCENP targets Aurora B to centromeres and central spindle. Immunofluorescence colocalization, library screening and RT-PCR for human gene identification Chromosoma Medium 11453556
2001 INCENP targets to the cleavage furrow by binding directly to beta-tubulin via a conserved domain (residues 48-85); this targeting requires dynamic microtubules but not F-actin; INCENP bundles microtubules when expressed in interphase cells. Yeast two-hybrid, in vitro microtubule binding/bundling assay, pharmacological perturbation (nocodazole, cytochalasin D), immunofluorescence Experimental cell research High 11139336
2001 Sli15 (yeast INCENP) stimulates the in vitro kinase activity of Ipl1 (yeast Aurora B); the Ipl1-binding and -stimulating activity of Sli15 resides within the metazoan INCENP homology region. Ipl1-Sli15 and Dam1 (a microtubule-binding protein) interact; Sli15 facilitates Ipl1 association with the mitotic spindle; both Sli15 and Ipl1 bind microtubules directly in vitro and associate with centromeric DNA in vivo. In vitro kinase assay, Co-immunoprecipitation, chromatin immunoprecipitation, microtubule binding assay The Journal of cell biology High 11724818
2002 The C. elegans Aurora B kinase AIR-2 phosphorylates the C. elegans INCENP ICP-1 at two adjacent serines in the C-terminus; ICP-1 (full-length and C-terminal fragment) stimulates AIR-2 kinase activity; this stimulation requires AIR-2 phosphorylation of ICP-1, as mutation of both serines abolishes the potentiation, establishing a positive feedback loop for Aurora B kinase activation by INCENP phosphorylation. In vitro kinase assay, site-directed mutagenesis, phosphorylation site mapping The Journal of biological chemistry High 12048181
2002 All detectable Survivin in Xenopus early embryo is in a complex with both Aurora B and INCENP throughout the cell cycle; Survivin and Aurora B bind different domains on INCENP; Survivin binding stimulates Aurora B activity >10-fold in mitotic extracts; this activation is phosphatase sensitive; hydrodynamic properties of the Aurora B/Survivin/INCENP complex are cell-cycle regulated. Co-immunoprecipitation, Xenopus egg extract fractionation, in vitro kinase assay, sucrose gradient sedimentation Molecular biology of the cell High 12221116
2002 INCENP directly stimulates Aurora B kinase activity; the C-terminal region of INCENP is sufficient for Aurora B activation; Aurora B phosphorylates INCENP at three consecutive residues (Thr893, Ser894, Ser895); a nonphosphorylatable mutant (TSS893-895AAA) is a poor activator of Aurora B, demonstrating that INCENP phosphorylation is important for kinase activation. Dominant-negative Aurora B impairs localization of the entire Aurora B/INCENP/survivin complex. Recombinant protein kinase assay, mass spectrometry phosphorylation site identification, site-directed mutagenesis, RNAi depletion, immunofluorescence Molecular biology of the cell High 12925766
2002 The INCENP-Aurora B kinase complex (ISWI-aurora B) phosphorylates histone H3 during mitosis in Xenopus egg extracts and controls the cell-cycle-regulated association of ISWI chromatin remodeling complexes with chromatin. Xenopus egg extract fractionation, INCENP-aurora B depletion, histone H3 phosphorylation assay Molecular biology of the cell Medium 11809820
2002 In yeast, the Ipl1-Sli15 (Aurora B-INCENP) complex promotes chromosome bi-orientation by facilitating turnover of kinetochore-spindle pole connections; ipl1 mutants fail to detach kinetochores from old spindle pole bodies, whereas wild-type cells show equal reattachment to old and new SPBs. Genetic analysis with unreplicated chromosome system, live-cell imaging, epistasis Cell High 11853667
2003 The conserved phosphatase Cdc14, activated by separase at anaphase onset, dephosphorylates yeast INCENP ortholog Sli15, directing the Sli15-Ipl1 complex from kinetochores to spindle microtubules during anaphase; this establishes the mechanistic trigger for metaphase-to-anaphase transfer of the INCENP-Aurora complex. Epistasis analysis, phosphatase assay, immunofluorescence localization in yeast mutants, in vitro dephosphorylation Science (New York, N.Y.) High 14605209
2003 Aurora B phosphorylates Survivin at Thr117 in vitro; a phosphomimetic T117E mutant fails to localize correctly in mitosis and cannot co-immunoprecipitate INCENP in vivo, suggesting Aurora B phosphorylation of Survivin regulates INCENP-Survivin interaction and passenger complex targeting. In vitro kinase assay, site-directed mutagenesis, immunofluorescence, co-immunoprecipitation The Journal of biological chemistry High 14610074
2003 CSC-1 (Borealin ortholog in C. elegans) binds directly to BIR-1 (Survivin) in vitro; the CSC-1/BIR-1 complex, but not individual subunits, associates with ICP-1 (INCENP); ICP-1 dramatically stimulates AIR-2 (Aurora B) kinase activity whereas CSC-1/BIR-1 does not, indicating they serve as targeting subunits; all four subunits are interdependent for localization. In vitro binding, in vitro kinase assay, RNAi, immunofluorescence The Journal of cell biology High 12707312
2004 Human Aurora C forms a complex with Aurora B and INCENP; INCENP binds and activates Aurora C in vivo and in vitro; Aurora C co-expressed with INCENP elicits phosphorylation of endogenous histone H3. Co-immunoprecipitation, in vitro kinase assay, immunofluorescence, transfection The Journal of biological chemistry High 15316025
2005 Crystal structure of Aurora B in complex with the IN-box segment of INCENP and the inhibitor Hesperadin: INCENP forms a crown around the small lobe of Aurora B and allosterically induces the active conformation of the T loop; phosphorylation of two serines in the INCENP C-terminus generates the fully active kinase; this mechanism is fundamentally different from the Aurora A:TPX2 activation mechanism. X-ray crystallography, in vitro kinase assay Molecular cell High 15866179
2005 CDK1 phosphorylates INCENP at Thr59 and Thr388, regulating Aurora B localization/activity from prophase to metaphase; phosphorylation at Thr388 (not Thr59) is required for Plk1 recruitment to the kinetochore; INCENP T388A replacement delays metaphase-to-anaphase transition; Aurora B, Plk1, and INCENP form a complex. Site-directed mutagenesis, in vitro kinase assay, RNAi rescue, immunofluorescence, co-immunoprecipitation Nature cell biology High 16378098
2005 INCENP is required for recruiting MKLP1 (mitotic kinesin-like protein) to the spindle midzone/midbody; RNAi of INCENP causes abnormal midzone/midbody formation and binucleated/multinucleated cells; RNAi of MKLP1 does not affect chromosome segregation but abrogates midbody formation. RNAi, immunofluorescence, live-cell imaging, 3D reconstruction The Biochemical journal High 15796717
2006 A ternary subcomplex of Survivin, Borealin, and the N-terminal 58 amino acids of INCENP is necessary and sufficient for targeting the chromosomal passenger complex (CPC) to the centromere; Aurora B is not required for centromere localization of this subcomplex; Borealin may direct the CPC to centromeric DNA directly. In vitro reconstitution, siRNA rescue with structure-based mutants, immunofluorescence, co-immunoprecipitation Molecular biology of the cell High 16571674
2006 INCENP and Aurora B are required for meiotic sister chromatid cohesion in Drosophila; INCENP physically binds the cohesion protector protein MEI-S332 (an excellent Aurora B substrate in vitro); an MEI-S332 mutant poorly phosphorylated by Aurora B is defective in centromere localization, implicating the CPC in direct regulation of meiotic cohesion via MEI-S332 phosphorylation. Genetic analysis of Drosophila incenp mutants, in vitro kinase assay, in vitro binding assay, immunofluorescence Developmental cell High 16824953
2007 Crystal structure (1.4 Å) of the Survivin-Borealin-INCENP N-terminal domain core complex 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 demonstrates that intertwined structural interactions create functional interdependence for CPC localization. X-ray crystallography, siRNA rescue with structure-based mutants, immunofluorescence 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 not required for INCENP redistribution from centromeres to central spindle but is required for subsequent cortical furrow targeting. Immunofluorescence, domain analysis, in vitro actin binding, Kif12 knockout analysis Molecular biology of the cell Medium 17567958
2009 INCENP-Aurora B interactions in vivo modulate the level of kinase activity to regulate CPC localization and checkpoint functions: low activity is sufficient for spindle checkpoint response to absent microtubules but not to low-dose taxol; intermediate activity is sufficient for taxol response but not for CPC transfer from chromosomes to anaphase spindle midzone (which requires high Aurora B activity). INCENP depletion and re-expression of activity mutants, Aurora B kinase activity measurement, immunofluorescence, taxol/nocodazole treatment The Journal of cell biology High 19951914
2009 INCENP plays a catalytic role in Aurora B autophosphorylation at Thr232 (activation loop): substoichiometric concentrations of INCENP are sufficient for Aurora B autophosphorylation; Aurora B/INCENP-catalyzed substrate phosphorylation proceeds through a rapid equilibrium random Bi Bi kinetic mechanism. In vitro kinase assay with substoichiometric INCENP, kinetic analysis, mass spectrometry The Biochemical journal High 18767990
2010 Cdc14-mediated dephosphorylation of Sli15 (INCENP) at anaphase onset prevents the mitotic checkpoint from re-engaging when tension between sister chromatids is lost; this represents an evolutionarily conserved mechanism (Sli15 dephosphorylation-dependent relocation from centromeres to central spindle is seen from yeast to human). Genetic epistasis in budding yeast, immunofluorescence, checkpoint assays Current biology : CB High 20619650
2011 Ipl1/Aurora-dependent phosphorylation of Sli15/INCENP prevents CPC binding to the preanaphase spindle and to the central spindle until late anaphase, modulating microtubule dynamics; decreased Ipl1-dependent phosphorylation drives direct CPC binding to microtubules, revealing how CPC influences microtubule dynamics. Cdk1 and Ipl1 cooperatively control microtubule dynamics through INCENP phosphorylation. Yeast genetics, phosphorylation site mutagenesis, in vitro microtubule binding, live-cell imaging The Journal of cell biology High 21727193
2012 Crystal structure of human Aurora B kinase domain in complex with human INCENP C-terminal Aurora-binding region reveals a dimeric arrangement confirmed by analytical ultracentrifugation; INCENP binding differs significantly from that seen in the Xenopus Aurora B:INCENP complex. X-ray crystallography, analytical ultracentrifugation Journal of medicinal chemistry High 22920039
2014 Structure of Xenopus Aurora B-INCENP complex bound to barasertib reveals the first structure with this clinically relevant inhibitor; an unexpected crystal-packing contact shows the INCENP C-terminus occupying the substrate-binding region, resembling a PKA-like trans-inhibitory mechanism. X-ray crystallography Acta crystallographica. Section F, Structural biology communications Medium 24598913
2015 The central region of INCENP (213 residues) is a ~32-nm-long single α-helix (SAH) domain, not a coiled coil; the N-terminal half of the SAH directly binds microtubules in vitro; the SAH may stretch up to ~80 nm under physiological forces, acting as a flexible 'dog leash' allowing Aurora B to phosphorylate outer kinetochore substrates while anchored to inner centromere heterochromatin. Biophysical characterization (SAH identification), in vitro microtubule binding assay, INCENP mutagenesis and cell biology The Journal of biological chemistry High 26175154
2015 PRMT1 methylates INCENP at Arg887 in the Aurora B-binding region, both in vitro and in vivo; R887-methylated INCENP has lower binding affinity to Aurora B in the presence of PRMT1; PRMT1 knockdown or overexpression of methylation-inactive INCENP attenuates Aurora B activity, causing abnormal chromosome alignment/segregation and reduced cancer cell growth. In vitro methylation assay, in vivo mass spectrometry, Co-immunoprecipitation, siRNA knockdown, chromosome alignment assay Oncotarget High 26460953
2015 The CPC multimerizes via INCENP's centromere-targeting domain (CEN box), increasing the microtubule-binding (MTB) affinity of INCENP; in (pro)metaphase, CEN box affinity for centromeres outcompetes MTB affinity; at anaphase onset, when H2AT120 is dephosphorylated, INCENP and Aurora B switch from centromere to microtubule localization. The INCENP coiled-coil/SAH domain drives midzone localization via direct electrostatic interaction with microtubules. In vitro microtubule binding, INCENP mutagenesis, siRNA rescue, immunofluorescence Cell reports High 26166576
2016 INCENP binds actin directly; this INCENP-actin interaction is important for cytokinesis and for midzone microtubule stabilization following furrow ingression; midzone MT stabilization is dependent on actomyosin contraction and Aurora B kinase activity, revealing a feedback between furrowing and microtubule dynamics mediated by the CPC. In vitro actin binding assay, INCENP actin-binding mutant expression, live-cell imaging, taxol rescue experiment Current biology : CB High 26898472
2016 LATS1 and LATS2 tumor suppressor kinases phosphorylate INCENP at Ser894 in the TSS motif; this LATS-mediated phosphorylation is necessary and sufficient for Aurora B activation required for cytokinesis completion in cells undergoing multipolar division. In vitro kinase assay, site-directed mutagenesis, immunofluorescence, RNAi Heliyon Medium 27512725
2017 The INCENP SAH domain supports CPC localization to chromatin and the mitotic checkpoint in addition to Survivin and Borealin; INCENP SAH-mediated 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 domain deletion/mutation analysis, immunofluorescence, mitotic arrest assays, microtubule binding The Journal of cell biology High 28314740
2017 In budding yeast, an engineered minimal CPC consisting of dimerized Sli15/INCENP C-terminal fragment and Ipl1/Aurora B suppresses bi-orientation defects; artificial dimerization promotes spindle association but not kinase activation clustering; a putative helical domain in Sli15 is essential for targeting kinetochore substrates even when dimerized, suggesting spindle association is important for Aurora B to preferentially destabilize misattached kinetochores. Protein engineering (artificial dimerization), yeast genetics, in vitro kinase assay, immunofluorescence The Journal of cell biology High 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) in budding yeast; this centromere/inner kinetochore localization of Ipl1-Sli15 is required for chromosome bi-orientation (demonstrated by engineered recruitment rescue). Co-immunoprecipitation, immunofluorescence, engineered kinetochore recruitment, yeast genetics Current biology : CB High 31006569
2019 Crystal structures of fully active Aurora C bound to phosphorylated INCENP (phospho-TSS motif) reveal that TSS motif phosphorylation stabilizes the kinase activation loop of Aurora C; TSS phosphorylations alter the substrate-binding surface consistent with altered substrate selectivity; VX-680 disrupts binding of the phosphorylated INCENP TSS motif to Aurora kinases. X-ray crystallography, in vitro kinase assay, native mass spectrometry Nature communications High 31320618
2019 A conserved acidic STD-rich motif of INCENP is phosphorylated during mitosis in vivo and by Plk1 in vitro; phosphomimetic mutations of this motif rescue cytokinesis and induce ectopic furrows and contractile ring formation in a Plk1- and ROCK1-dependent manner independent of cell cycle and microtubule status; nonphosphorylatable INCENP STD motif disrupts chromosome congression. In vitro kinase assay (Plk1 on INCENP STD motif), conditional-knockout cell line, INCENP mutant rescue, live-cell imaging, immunofluorescence Journal of cell science High 31601613
2021 An ATM-Chk2-INCENP pathway imposes the abscission checkpoint: ATM activates Chk2 at late midbodies; Chk2 phosphorylates INCENP Ser91, promoting INCENP binding to Mklp2 kinesin and CPC localization to the midbody center via Mklp2-Cep55 association; nonphosphorylatable INCENP-Ser91A impairs CPC midbody localization and accelerates abscission; phosphomimetic INCENP-Ser91D rescues abscission delay in ATM- or Chk2-deficient cells. Kinase inhibition, siRNA, phosphomimetic/nonphosphorylatable INCENP mutants, co-immunoprecipitation, immunofluorescence, live-cell imaging, abscission timing assays The Journal of cell biology High 33355621
2021 Phosphorylation of INCENP's intrinsically disordered region (IDR) expands its conformational ensemble by increasing net charge; the IDR undergoes globule-to-coil conformational transitions that non-monotonically depend on phosphorylation degree; phosphorylation regulates IDR cohesiveness and phase behavior, potentially modulating Aurora B's reach to its targets via the 'dog-leash' mechanism. All-atom and coarse-grain molecular dynamics simulations Journal of molecular biology Low 34883116
2025 Cryo-EM structure of CPC (Borealin-Survivin-INCENP N-terminus) bound to H3Thr3-phosphorylated nucleosome reveals multipartite interactions including engagement at the nucleosome acidic patch and DNA entry-exit site; perturbing CPC-nucleosome interaction compromises protection against MNase digestion in vitro and centromeric chromatin stability in cells, uncovering a non-catalytic role for CPC in maintaining centromeric chromatin. Cryo-EM structure determination, atomic force microscopy, biochemical MNase protection assay, cellular assays of centromere stability bioRxivpreprint High bio_10.1101_2025.05.15.654082
2025 Cryo-EM structure of the CPC targeting module (Survivin-Borealin-INCENP N-terminus) in complex with haspin-phosphorylated H3pT3-nucleosome: the N-terminus of Borealin and the Survivin BIR domain act as a pivot and flexible tethering point, respectively, increasing CPC affinity for H3pT3 nucleosomes without restricting orientation; this 'pivot-tether' arrangement is important for spindle assembly checkpoint control by Aurora B. Cryo-EM structure determination, mutagenesis, spindle assembly checkpoint assays bioRxivpreprint High bio_10.1101_2025.01.22.634029

Source papers

Stage 0 corpus · 81 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 602 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 440 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 398 11352945
1987 The inner centromere protein (INCENP) antigens: movement from inner centromere to midbody during mitosis. The Journal of cell biology 353 3316246
2005 Mechanism of Aurora B activation by INCENP and inhibition by hesperadin. Molecular cell 335 15866179
2007 Structure of a Survivin-Borealin-INCENP core complex reveals how chromosomal passengers travel together. Cell 285 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 272 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 238 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 227 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 183 9864353
2005 Complex formation of Plk1 and INCENP required for metaphase-anaphase transition. Nature cell biology 155 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 117 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
1999 Defective chromosome segregation, microtubule bundling and nuclear bridging in inner centromere protein gene (Incenp)-disrupted mice. Human molecular genetics 85 10369859
2012 Crystal structure of human aurora B in complex with INCENP and VX-680. Journal of medicinal chemistry 83 22920039
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
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 81 12707312
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 58 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 52 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 36 23562843
2017 Dual recognition of chromatin and microtubules by INCENP is important for mitotic progression. The Journal of cell biology 34 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 32 24598913
2015 PRMT1 promotes mitosis of cancer cells through arginine methylation of INCENP. Oncotarget 31 26460953
2011 Female gametophytic cell specification and seed development require the function of the putative Arabidopsis INCENP ortholog WYRD. Development (Cambridge, England) 31 21752930
2010 Centromere localization of INCENP-Aurora B is sufficient to support spindle checkpoint function. Cell cycle (Georgetown, Tex.) 25 20372054
2019 Targeting the Chromosomal Passenger Complex Subunit INCENP Induces Polyploidization, Apoptosis, and Senescence in Neuroblastoma. Cancer research 24 31416840
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
2008 Perturbation of Incenp function impedes anaphase chromatid movements and chromosomal passenger protein flux at centromeres. Chromosoma 23 18784935
2017 An engineered minimal chromosomal passenger complex reveals a role for INCENP/Sli15 spindle association in chromosome biorientation. The Journal of cell biology 22 28314741
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