Affinage

CENPE

Centromere-associated protein E · UniProt Q02224

Length
2701 aa
Mass
316.4 kDa
Annotated
2026-04-28
100 papers in source corpus 44 papers cited in narrative 44 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CENP-E is a kinesin-7 family plus-end-directed motor protein that functions as a central organizer of kinetochore–microtubule attachment, chromosome congression, and mitotic checkpoint signaling during cell division. It localizes to the fibrous corona of kinetochores from prometaphase through anaphase, where it transports pole-proximal chromosomes toward the metaphase plate along spindle microtubules, converts lateral kinetochore–microtubule attachments to stable end-on attachments through a tethered tip-tracking mechanism requiring both its N-terminal motor and C-terminal microtubule-binding domains, and directly activates BubR1 checkpoint kinase activity—silencing it upon microtubule capture in a ternary CENP-E–BubR1–microtubule complex that couples attachment status to checkpoint signaling (PMID:9363944, PMID:16144904, PMID:23955301, PMID:11030625). CENP-E additionally recruits PP1 phosphatase and CLASP1/2 to kinetochores, delivers dynein–dynactin loading at the corona, and organizes PRC1 into the central spindle at mitotic exit (PMID:20691903, PMID:19733075, PMID:37984321, PMID:31174204). Its activity and localization are regulated by autoinhibition relieved by Aurora A/B and CDK1 phosphorylation, SUMO-2/3 modification enabling kinetochore targeting via Nuf2 poly-SUMO chains, linear ubiquitination by LUBAC anchoring it to attached kinetochores through KNL1, and cell-cycle-dependent proteasomal degradation at M/G1 (PMID:18342609, PMID:37658044, PMID:18374647, PMID:33910471, PMID:30655516, PMID:8207059).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 1991 High

    Establishing that a novel centromere protein is required for mitotic progression answered whether kinetochores harbor dedicated proteins that control the metaphase-to-anaphase transition, founding the CENP-E field.

    Evidence Monoclonal antibody generation, immunofluorescence localization to kinetochores, and microinjection blocking anaphase entry in cultured cells

    PMID:2022189

    Open questions at the time
    • Motor identity unknown
    • Mechanism of anaphase block not defined
    • No molecular cloning yet performed
  2. 1992 High

    Cloning CENP-E revealed it encodes a kinesin-like motor protein that accumulates in G2 and is degraded after mitosis, establishing that a dedicated motor links kinetochore function to cell-cycle-regulated proteolysis.

    Evidence Molecular cloning from HeLa cells, sequence analysis revealing kinesin motor domain, cell-cycle staging by immunofluorescence and immunoblot

    PMID:1406971

    Open questions at the time
    • Direction of motor movement unknown
    • Identity of degradation pathway not established
  3. 1994 High

    Defining a second C-terminal microtubule-binding site and its CDK1-dependent phosphoregulation revealed how CENP-E cross-links midzone microtubules only after cyclin B destruction, answering how anaphase-specific midzone organization is temporally controlled.

    Evidence In vitro microtubule binding assays with domain fragments, MPF/CDK1 phosphorylation assay inhibiting C-terminal binding

    PMID:8023161 PMID:8207059

    Open questions at the time
    • In vivo relevance of CDK1 phospho-switch not tested
    • Identity of degradation machinery unknown
  4. 1997 High

    Demonstrating that CENP-E is a plus-end-directed motor essential for metaphase chromosome alignment, and that it resides on corona fibers of the outermost kinetochore, established CENP-E as the congression motor and defined its ultrastructural position.

    Evidence Immunodepletion from Xenopus egg extracts blocking congression, in vitro motility assay showing plus-end directionality, immunoelectron microscopy localizing CENP-E to corona fibers

    PMID:9334346 PMID:9363944 PMID:9396744

    Open questions at the time
    • How CENP-E couples to depolymerizing ends in vivo not resolved
    • Relationship to checkpoint signaling not yet addressed
  5. 1998 High

    Identifying BubR1 and CENP-F as direct kinetochore-binding partners of CENP-E linked the congression motor to mitotic checkpoint components, raising the possibility that CENP-E transduces attachment status to checkpoint kinases.

    Evidence Yeast two-hybrid screen with CENP-E kinetochore-binding domain, reciprocal co-immunoprecipitation from HeLa mitotic extracts

    PMID:9763420

    Open questions at the time
    • Whether CENP-E directly regulates BubR1 kinase activity unknown
    • Direction of dependency (which recruits which) not resolved
  6. 2000 High

    Showing that CENP-E is stoichiometrically associated with BubR1 and required for both establishing and maintaining the spindle checkpoint placed CENP-E at the kinetochore-based origin of checkpoint signal generation, upstream of MAD2.

    Evidence Immunodepletion from Xenopus extracts abolishing nocodazole arrest rescued by excess MAD2; stoichiometric co-IP of CENP-E–BubR1 from mitotic HeLa cells; antisense suppression producing chronic mono-orientation and checkpoint activation

    PMID:10934468 PMID:11030625

    Open questions at the time
    • Enzymatic mechanism of BubR1 activation/silencing by CENP-E not demonstrated
    • How CENP-E senses microtubule attachment biochemically unclear
  7. 2002 High

    Conditional knockout in mice showed CENP-E-free kinetochores capture only half the normal microtubule complement and cause embryonic lethality, providing genetic proof that CENP-E is essential for stable kinetochore–microtubule attachment in vivo.

    Evidence Conditional gene knockout in mouse embryos and tissues, electron microscopy quantifying kinetochore microtubule number

    PMID:12361599

    Open questions at the time
    • Whether reduced microtubule number reflects capture vs. retention defect unclear
    • Tissue-specific phenotypes not fully characterized
  8. 2005 High

    Reconstituting the CENP-E–BubR1–microtubule ternary complex in vitro demonstrated that CENP-E binding directly activates BubR1 kinase and microtubule capture silences it, establishing the molecular switch that converts mechanical attachment into a biochemical checkpoint signal.

    Evidence In vitro kinase assay with purified BubR1, CENP-E, and microtubules showing direct enzymatic activation and silencing

    PMID:16144904

    Open questions at the time
    • In vivo phosphorylation targets of activated BubR1 not mapped
    • Whether silencing is purely steric or involves conformational change unknown
  9. 2008 High

    Three concurrent studies established that full-length CENP-E is autoinhibited by tail–motor interaction, is a slow processive motor with a 230-nm flexible coiled-coil stalk, and requires SUMO-2/3 modification for kinetochore targeting—collectively defining CENP-E as a regulatable flexible tether rather than a fast transporter.

    Evidence Purified full-length Xenopus CENP-E motor assays with tail inhibition and MPS1/CDK1 activation; single-molecule fluorescence and EM; SUMO modification assays with SIM mutagenesis

    PMID:18342609 PMID:18374647 PMID:18427114 PMID:18443223

    Open questions at the time
    • In vivo kinase responsible for relieving autoinhibition at specific cell-cycle stages not resolved
    • SUMO E3 ligase identity not established
    • Structural basis of autoinhibition not determined
  10. 2010 High

    Identifying Aurora A/B phosphorylation of CENP-E as a switch that disrupts PP1 binding revealed a dual mechanism: Aurora activity at poles releases CENP-E for chromosome towing, while PP1 delivery by CENP-E to kinetochores stabilizes end-on attachments.

    Evidence In vitro kinase and PP1-binding assays, phospho-mutant rescue in cells, live imaging of polar chromosome congression

    PMID:20691903

    Open questions at the time
    • How PP1 delivered by CENP-E is handed off to outer kinetochore substrates not defined
    • Relative contributions of Aurora A vs. B at different spindle locations not fully dissected
  11. 2013 High

    Single-molecule reconstitution showed CENP-E converts from lateral transporter to processive tip-tracker on both assembling and disassembling microtubule ends, requiring both motor and tail domains—answering how congressed chromosomes maintain dynamic plus-end attachment.

    Evidence Single-molecule TIRF and laser trapping of CENP-E on dynamic microtubules; high-resolution live imaging of lateral-to-end-on conversion in cells with CENP-E and MCAK perturbation

    PMID:23891108 PMID:23955301

    Open questions at the time
    • Structural basis of tip-tracking conformational switch not resolved
    • Contribution of BubR1 phosphorylation to this switch identified only later
  12. 2019 High

    Three studies revealed new layers of CENP-E regulation: BubR1 phosphorylation switches CENP-E from transporter to tip-tracker, LUBAC-mediated linear ubiquitination anchors CENP-E specifically at attached kinetochores via KNL1, and CENP-E motility reduces Aurora B phosphorylation of Ndc80 in a tension-independent manner.

    Evidence Crystal structure of BubR1 kinase domain with in vitro CENP-E phosphorylation and single-molecule validation; in vitro linear ubiquitination assay plus RNAi; SHREC microscopy with chemical perturbations

    PMID:30655516 PMID:31122175 PMID:31201382

    Open questions at the time
    • Whether BubR1 kinase activity is required in human cells (demonstrated in Drosophila) not confirmed
    • Mechanism by which CENP-E motility reduces Aurora B phosphorylation not structurally explained
    • Deubiquitinase counteracting LUBAC on CENP-E not identified
  13. 2021 High

    Demonstrating that poly-SUMO-2/3 chains on Nuf2 recruit CENP-E through its SIM identified the kinetochore receptor for SUMO-dependent CENP-E targeting, resolving how the 2008 SUMOylation requirement is implemented at the molecular level.

    Evidence SUMO fusion protein rescue assays, in vitro binding with trimeric SUMO-2–Nuf2 vs. SIM-mutant CENP-E, immunofluorescence

    PMID:33910471

    Open questions at the time
    • SUMO E3 ligase modifying Nuf2 not identified
    • Whether SUMO chain length is regulated during mitosis unknown
  14. 2023 High

    Three studies redefined CENP-E as an integrated corona scaffold: Aurora A/B relieve its autoinhibition and control corona disassembly, CENP-E retains the RZZ–Spindly complex and loads dynein–dynactin, and HPV16 E6 hijacks E6AP to degrade CENP-E causing chromosomal instability—expanding CENP-E's role from motor to bidirectional transport coordinator.

    Evidence Aurora kinase inhibitors with phospho-antibodies and live imaging; MPS1 inhibition with CENP-E RNAi epistasis; HPV16 E6 overexpression with proteasome inhibitor rescue and E6AP siRNA

    PMID:36989302 PMID:37658044 PMID:37984321

    Open questions at the time
    • Structural basis of CENP-E–RZZS interaction not determined
    • Whether E6AP-mediated CENP-E degradation occurs outside HPV context not established
    • Full corona disassembly pathway hierarchy not resolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • A complete structural model of full-length CENP-E (including the autoinhibited and active conformations), the identity of SUMO E3 ligases acting on CENP-E and Nuf2, and the precise mechanism by which CENP-E motility reduces Aurora B phosphorylation of kinetochore substrates remain unresolved.
  • No cryo-EM or crystal structure of full-length CENP-E or its autoinhibited state
  • SUMO E3 ligase for Nuf2 and CENP-E not identified
  • Mechanism coupling CENP-E movement to Aurora B substrate dephosphorylation structurally undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003774 cytoskeletal motor activity 4 GO:0008092 cytoskeletal protein binding 4 GO:0060090 molecular adaptor activity 2 GO:0140657 ATP-dependent activity 2
Localization
GO:0005694 chromosome 3 GO:0005856 cytoskeleton 3
Pathway
R-HSA-1640170 Cell Cycle 6 R-HSA-392499 Metabolism of proteins 4
Partners
BUB1BCENPFCLASP1CLASP2KNL1NKAPNUF2PRC1
Complex memberships
CENP-E–BubR1 checkpoint complexkinetochore fibrous corona

Evidence

Reading pass · 44 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1991 CENP-E is a novel centromere-associated protein that localizes to kinetochores from prometaphase through metaphase, relocates to the spindle midzone at anaphase, and is required for metaphase-to-anaphase transition; microinjection of anti-CENP-E antibody blocks or delays progression into anaphase. Monoclonal antibody generation, immunofluorescence, microinjection into metaphase cells The EMBO journal High 2022189
1992 CENP-E is a kinesin-like motor protein (M_r 312,000) that accumulates in G2 phase, associates with kinetochores during congression, relocates to the spindle midzone at anaphase, and is quantitatively degraded at the end of cell division. Molecular cloning, immunofluorescence, cell cycle staging Nature High 1406971
1994 CENP-E accumulates progressively across the cell cycle, peaking at ~22,000 molecules/cell in early mitosis, then is specifically degraded at the M/G1 transition after cyclin B proteolysis; degradation is independent of cytokinesis. Centrifugal elutriation cell cycle separation, immunoblotting, pulse-labeling with [35S]methionine The Journal of cell biology High 8207059
1994 CENP-E cross-links interdigitating microtubules at the spindle midzone via both an N-terminal motor-like site and a distinct 99-amino acid C-terminal microtubule-binding domain; phosphorylation of the C-terminus by MPF (maturation promoting factor/CDK1-cyclin B) inhibits this microtubule-binding activity before anaphase. In vitro microtubule binding assays, MPF phosphorylation assay, domain mapping Science High 8023161
1995 CENP-E couples chromosomes to depolymerizing microtubule ends; antibodies to the neck region of CENP-E completely stop depolymerization-dependent chromosome motion in vitro, while antibodies to the head or tail slow it ~threefold. In vitro chromosome motility assay with depolymerizing microtubules, domain-specific antibody inhibition The Journal of cell biology High 7822408
1997 CENP-E is a plus-end-directed kinetochore motor essential for metaphase chromosome alignment; immunodepletion from Xenopus egg extracts or antibody addition prevents chromosome positioning at the metaphase plate, and purified CENP-E powers movement toward microtubule plus ends in vitro. Immunodepletion from Xenopus egg extracts, antibody addition, in vitro microtubule motility assay Cell High 9363944
1997 CENP-E is an integral component of kinetochore corona fibers; immediately after nuclear envelope breakdown, a plus-end motor traffics cytoplasmic CENP-E toward chromosomes along astral microtubules, targeting it to the outermost kinetochore region before stable microtubule attachment. Immunoelectron microscopy The Journal of cell biology High 9334346
1997 CENP-E function at kinetochores is required for both monopolar chromosomes to establish bipolar microtubule connections and for bipolar chromosomes to align at the metaphase plate; the motor domain is necessary for both functions. Overexpression of a truncated CENP-E (lacking the N-terminal motor domain) competitively displaces endogenous CENP-E from kinetochores and blocks alignment. Antibody microinjection, dominant-negative overexpression, in vivo imaging The Journal of cell biology High 9396744
1998 CENP-E contains a 350-amino acid kinetochore-binding domain sufficient for mitotic (but not interphase) kinetochore targeting; this domain directly interacts with kinetochore proteins CENP-F and hBUBR1 (identified by yeast two-hybrid and confirmed by co-immunoprecipitation from HeLa cells). CENP-E and hBUBR1 assemble sequentially onto kinetochores and colocalize through mid-anaphase. Yeast two-hybrid screen, co-immunoprecipitation from HeLa cells, immunofluorescence The Journal of cell biology High 9763420
1998 Active MAP kinase (ERK1/2) localizes to kinetochores during mitosis and physically associates with CENP-E; MAP kinase phosphorylates CENP-E in vitro on sites known to regulate its microtubule interactions. Immunofluorescence with phospho-MAP kinase antibody, in vitro kinase assay, co-immunoprecipitation The Journal of cell biology Medium 9744883
1999 hBUBR1 monitors CENP-E-dependent kinetochore activities and is required to prevent premature anaphase; hBUBR1 kinase activity is stimulated after spindle disruption in mitosis, and hBUBR1 associates with the cyclosome/APC in mitotically arrested cells. Co-immunoprecipitation, kinase assays, dominant-negative and overexpression studies The Journal of cell biology High 10477750
2000 CENP-E is nearly stoichiometrically associated with the checkpoint kinase BubR1 during mitosis; suppression of CENP-E synthesis produces chronically mono-oriented chromosomes, spindle pole fragmentation, and profound checkpoint activation, indicating CENP-E links spindle microtubule attachment to mitotic checkpoint signaling. Antisense oligonucleotide suppression, immunoprecipitation from mitotic cells, immunofluorescence Nature cell biology High 10934468
2000 CENP-E is required for establishing and maintaining the mitotic checkpoint in Xenopus egg extracts; immunodepletion or antibody addition prevents spindle damage-induced arrest, which is restored by adding excess MAD2, demonstrating CENP-E acts at the kinetochore to generate the checkpoint signal but not in downstream signaling. CENP-E directly binds both spindle microtubules and BUBR1. Immunodepletion from Xenopus egg extracts, antibody addition, MAD2 rescue experiment Cell High 11030625
2000 CENP-E and CENP-F are farnesylated proteins; their prenylation is blocked by farnesyl transferase inhibitor SCH 66336, which does not prevent kinetochore localization but alters the association between CENP-E and microtubules. In vitro farnesylation assay, FTI treatment, immunohistochemistry The Journal of biological chemistry Medium 10852915
2002 Selective mouse CENP-E gene deletion shows that CENP-E-free kinetochores bind only half the normal number of microtubules and some chromosomes remain juxtaposed to spindle poles; embryonic deletion causes early developmental arrest and tissue-specific deletion leads to chromosome missegregation, establishing CENP-E's role in stable microtubule capture. Conditional gene knockout in mice, electron microscopy, immunofluorescence Developmental cell High 12361599
2003 Aurora B kinase activity is required for kinetochore localization of CENP-E (as well as BubR1 and Mad2); inhibition of Aurora B with ZM447439 diminishes CENP-E at kinetochores and compromises the spindle checkpoint. Aurora kinase inhibitor (ZM447439) treatment, RNA interference, immunofluorescence The Journal of cell biology High 12719470
2003 Human MPS1 (hMPS1/TTK) is required for mitotic arrest induced by loss of CENP-E from kinetochores; hMPS1 interacts with kinetochores in a microtubule occupancy-sensitive manner and is required for MAD1/MAD2 (but not BubR1) kinetochore binding downstream of CENP-E. Dominant-negative constructs, immunofluorescence, co-immunoprecipitation Molecular biology of the cell Medium 12686615
2004 Crystal structure of the human CENP-E motor domain with MgADP bound at 2.5 Å resolution reveals the linker region in a 'docked' conformation identical to conventional kinesin, with structural differences from Eg5; this establishes the active site architecture for drug targeting. X-ray crystallography Journal of molecular biology High 15236970
2004 Bub1 is required for kinetochore localization of CENP-E (as well as CENP-F, BubR1, and Mad2) in human somatic cells; RNAi depletion of Bub1 prevents CENP-E from reaching kinetochores and increases lagging chromosomes. RNA interference, immunofluorescence Journal of cell science High 15020684
2005 Direct binding of BubR1 to CENP-E activates BubR1 kinase activity; microtubule capture by the CENP-E motor domain silences BubR1 kinase activity in a ternary CENP-E–BubR1–microtubule complex, establishing CENP-E as the signal transducing linker that silences mitotic checkpoint signaling upon microtubule attachment. In vitro kinase assay with purified BubR1, microtubules, and CENP-E; motorless fragment overexpression The Journal of cell biology High 16144904
2006 CENP-E interacts with Skp1 at the midbody through its coiled-coil domain; Skp1 arrives after CENP-E and promotes CENP-E degradation at the midbody, which is essential for cytokinesis completion. Yeast two-hybrid, in vitro binding, co-immunoprecipitation, siRNA knockdown, immunofluorescence Biochemical and biophysical research communications Medium 16682006
2008 CENP-E is specifically modified by SUMO-2/3 (not SUMO-1) and possesses SUMO-2/3 polymeric chain-binding activity essential for kinetochore localization; global inhibition of SUMOylation causes prometaphase arrest due to loss of CENP-E kinetochore targeting. SUMO modification assays, SUMO-interacting motif mutagenesis, immunofluorescence, SUMOylation inhibition Molecular cell High 18374647
2008 Full-length CENP-E is autoinhibited: the tail domain directly blocks motor activity via interaction with the motor domain; MPS1 or CDK1-cyclin B phosphorylation of the tail relieves this autoinhibition and activates plus-end-directed motility in vitro. Purified full-length Xenopus CENP-E motor assays, tail-domain inhibition experiments, phosphorylation by MPS1 and CDK1-cyclin B in vitro Molecular cell High 18342609
2008 Full-length CENP-E is a slow (~0.5–2 nm/s), highly processive plus-end-directed motor; single-molecule assays reveal it is a 230-nm flexible coiled-coil separating kinetochore-binding and motor domains, allowing it to serve as a flexible motile tether linking kinetochores to dynamic microtubule plus ends. Single-molecule fluorescence assays, electron microscopy of full-length Xenopus CENP-E The Journal of cell biology High 18443223
2008 CENP-E is a processive transport motor that moves toward microtubule plus ends in a hand-over-hand fashion with 8-nm steps, stall force of ~6 pN, average run length of ~2.6 μm, and K_M,ATP of ~35 μM. Single-molecule FIONA assay, optical trapping PNAS High 18427114
2009 CENP-E recruits both CLASP1 and CLASP2 to kinetochores independently of its motor activity or microtubule presence; depletion of either CLASPs or CENP-E comparably reduces kinetochore microtubule poleward flux and turnover. Proteomic interaction screen (MS), co-immunoprecipitation, RNAi depletion, microtubule dynamics measurements Current biology High 19733075
2010 Aurora A and B phosphorylate a conserved residue on CENP-E; PP1 binds CENP-E via a motif overlapping this phosphorylation site, and Aurora phosphorylation disrupts PP1 binding, reducing CENP-E's microtubule affinity. This Aurora/PP1 switch at spindle poles is required for CENP-E-mediated towing of polar chromosomes, and PP1 delivery by CENP-E to the outer kinetochore is necessary for stable microtubule capture. In vitro kinase assay, phospho-specific antibodies, PP1 binding assays, RNAi rescue with phospho-mutants, live imaging Cell High 20691903
2010 CENP-E promotes microtubule plus-end elongation in vitro; 60% of polarity-marked microtubules show CENP-E-promoted plus-end elongation at a rate of ~1.48 μm/30 min requiring ATP hydrolysis, with CENP-E enriched at elongating plus ends. In vitro microtubule gliding assay, real-time microscopy with polarity-marked microtubules Current biology Medium 20797864
2011 CENP-E interacts with SKAP via its C-terminal tail; SKAP binds microtubules in vitro and this interaction is synergized by CENP-E; depletion of SKAP or CENP-E reduces inter-kinetochore tension and causes chromosome missegregation. Co-immunoprecipitation, in vitro binding, immunoelectron microscopy, RNAi The Journal of biological chemistry Medium 22110139
2013 After chromosomes congress, CENP-E converts from a lateral microtubule transporter to a processive tip-tracker that maintains association with both assembling and disassembling microtubule tips through a tethered motor mechanism requiring both motor and tail domains. Single-molecule TIRF assays, laser trapping, computational modeling Nature cell biology High 23955301
2013 CENP-E mediates lateral-to-end-on kinetochore–microtubule attachment conversion by tethering the lateral kinetochore to microtubule walls; MCAK-mediated microtubule depolymerization releases laterally attached microtubules after partial end-on attachment. High-resolution live imaging assay, RNAi depletion of CENP-E and MCAK Current biology High 23891108
2013 The C-terminal non-motor domain of CENP-E binds microtubules with affinity similar to the Ndc80 complex; electron microscopy shows this domain engages the microtubule surface in a disordered manner, consistent with facilitating initial lateral attachments. Biochemical microtubule binding assays, negative-stain electron microscopy Journal of molecular biology Medium 23892111
2014 The elongated coiled-coil stalk of CENP-E is required for kinetochore-microtubule end-on attachment; 'Bonsai' CENP-E with shortened stalk fails to bind microtubules in vitro without cargo binding and causes chromosome misalignment and lagging chromosomes in cells. In vitro single-molecule motility assays with truncation mutants, live cell imaging of stalk-shortened CENP-E Molecular biology of the cell High 24920822
2015 CTCF interacts with CENP-E both in vitro and in vivo; CTCF binds to pericentric/centromeric DNA via its C-terminal fingers and recruits CENP-E to these regions early in mitosis; overexpression of a CTCF-targeted CENP-E fragment delays chromosome alignment. Co-immunoprecipitation, ChIP, overexpression experiments, immunofluorescence Cell reports Medium 26321640
2016 SUMOylated NKAP anchors CENP-E to kinetochores; Bub3 recruits NKAP to stabilize CENP-E–BubR1 binding at kinetochores; a SUMOylation-deficient NKAP mutant cannot support CENP-E kinetochore localization; NKAP is SUMOylated predominantly in mitosis. RNAi knockdown, co-immunoprecipitation, immunofluorescence, SUMO mutant rescue Nature communications High 27694884
2018 CENP-E and CENP-F interact directly and specifically with BUBR1 and BUB1, respectively; biochemical reconstitution demonstrates these are direct interactions requiring a dimeric coiled-coil in CENP-E/CENP-F and the kinase domain of BUBR1/BUB1; BUBR1 is dispensable for CENP-E kinetochore localization but BUB1 is required for CENP-F localization. Biochemical reconstitution, yeast two-hybrid, immunofluorescence, RNAi The Journal of biological chemistry High 29748388
2019 BubR1 phosphorylates CENP-E to switch it from a lateral microtubule transporter to a plus-end tip-tracker; BubR1 kinase domain structure (from Drosophila) reveals a catalytically active conformation; inhibition of this phosphorylation prevents proper microtubule capture and central spindle assembly. Crystal structure of BubR1 kinase domain, in vitro kinase assay with CENP-E substrate, single-molecule assays, bubristatin inhibitor Cell research High 31201382
2019 LUBAC catalyzes linear ubiquitination of CENP-E, which is specifically required for CENP-E localization to attached (not unattached) kinetochores; KNL1 acts as a receptor for linear ubiquitin chains to anchor CENP-E at attached kinetochores. In vitro ubiquitination assay, co-immunoprecipitation, RNAi, immunofluorescence Nature communications High 30655516
2019 CENP-E motor motility mediates a tension-independent reduction in Aurora B-mediated phosphorylation of outer kinetochore components (Ndc80); CENP-E undergoes structural rearrangements upon microtubule capture detected by SHREC microscopy, dependent on its flexible coiled-coil. Single-molecule high-resolution colocalization (SHREC) microscopy, chemical inhibition of CENP-E motor and Aurora B Cell cycle Medium 31122175
2020 CENP-E forms a complex with PRC1 in mitotic cells and is required for temporal assembly of PRC1 to the spindle midzone; chemical inhibition of CENP-E in metaphase prevents accurate central spindle assembly, revealing a role for CENP-E in organizing kinetochore microtubules into stable midzone arrays. Biotinylated syntelin affinity pulldown, co-immunoprecipitation, light sheet microscopy, 3D organoids Journal of molecular cell biology Medium 31174204
2021 Poly-SUMO-2/3 chain modification of the kinetochore protein Nuf2 facilitates CENP-E kinetochore localization through CENP-E's SUMO-interacting motif (SIM); trimeric SUMO-2 chain-modified Nuf2 shows higher binding affinity to wild-type CENP-E but not SIM-mutant CENP-E. SUMO fusion protein rescue assays, in vitro binding assays, immunofluorescence, mutagenesis of CENP-E SIM Cell cycle High 33910471
2023 HPV16 E6 causes degradation of CENP-E in a proteasome-dependent manner via the ubiquitin ligase E6AP/UBE3A, independently of p53; CENP-E degradation produces chronically misaligned polar chromosomes and chromosomal instability. HPV16 E6 overexpression, proteasome inhibitor rescue, E6AP siRNA, immunofluorescence, patient tumor analysis PNAS High 36989302
2023 Aurora A and B kinases phosphorylate CENP-E to release it from autoinhibition; at kinetochores Aurora B prevents premature CENP-E removal by dynein, while at spindle poles Aurora A promotes chromosome congression; this Aurora A/B–CENP-E axis drives fibrous corona disassembly. Aurora kinase inhibitors, phospho-specific antibodies, live imaging, immunofluorescence in human cells Nature communications High 37658044
2023 CENP-E is required to retain the RZZ–Spindly (RZZS) complex at kinetochores when MPS1-dependent corona assembly is prevented; conversely with active MPS1, CENP-E is strictly required for physiological dynein–dynactin kinetochore loading, identifying CENP-E as an integrated scaffold coordinating bidirectional motor transport in the corona. MPS1 inhibition, CENP-E RNAi, phosphomimetic RZZS mutants, immunofluorescence The EMBO journal High 37984321

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2003 Aurora B couples chromosome alignment with anaphase by targeting BubR1, Mad2, and Cenp-E to kinetochores. The Journal of cell biology 1049 12719470
1992 CENP-E is a putative kinetochore motor that accumulates just before mitosis. Nature 373 1406971
1997 CENP-E is a plus end-directed kinetochore motor required for metaphase chromosome alignment. Cell 357 9363944
1991 CENP-E, a novel human centromere-associated protein required for progression from metaphase to anaphase. The EMBO journal 346 2022189
2000 CENP-E forms a link between attachment of spindle microtubules to kinetochores and the mitotic checkpoint. Nature cell biology 320 10934468
1999 Human BUBR1 is a mitotic checkpoint kinase that monitors CENP-E functions at kinetochores and binds the cyclosome/APC. The Journal of cell biology 314 10477750
2000 Farnesyl transferase inhibitors block the farnesylation of CENP-E and CENP-F and alter the association of CENP-E with the microtubules. The Journal of biological chemistry 292 10852915
2004 Bub1 is required for kinetochore localization of BubR1, Cenp-E, Cenp-F and Mad2, and chromosome congression. Journal of cell science 288 15020684
1997 CENP-E function at kinetochores is essential for chromosome alignment. The Journal of cell biology 275 9396744
2002 Unstable kinetochore-microtubule capture and chromosomal instability following deletion of CENP-E. Developmental cell 267 12361599
1998 Characterization of the kinetochore binding domain of CENP-E reveals interactions with the kinetochore proteins CENP-F and hBUBR1. The Journal of cell biology 239 9763420
2001 CENP-E is essential for reliable bioriented spindle attachment, but chromosome alignment can be achieved via redundant mechanisms in mammalian cells. Molecular biology of the cell 220 11553716
2008 SUMO-2/3 modification and binding regulate the association of CENP-E with kinetochores and progression through mitosis. Molecular cell 203 18374647
2010 Aurora kinases and protein phosphatase 1 mediate chromosome congression through regulation of CENP-E. Cell 199 20691903
1997 The microtubule-dependent motor centromere-associated protein E (CENP-E) is an integral component of kinetochore corona fibers that link centromeres to spindle microtubules. The Journal of cell biology 199 9334346
2001 Spindle checkpoint protein Bub1 is required for kinetochore localization of Mad1, Mad2, Bub3, and CENP-E, independently of its kinase activity. The Journal of cell biology 196 11402067
1998 Active MAP kinase in mitosis: localization at kinetochores and association with the motor protein CENP-E. The Journal of cell biology 196 9744883
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