Affinage

CENPT

Centromere protein T · UniProt Q96BT3

Length
561 aa
Mass
60.4 kDa
Annotated
2026-06-09
33 papers in source corpus 28 papers cited in narrative 29 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CENP-T is an inner kinetochore protein that physically links centromeric chromatin to the spindle microtubule-binding machinery during chromosome segregation (PMID:22304917, PMID:25660545). Its C-terminal histone fold domain coassembles with CENP-W, CENP-S and CENP-X into a stable heterotetramer that structurally resembles canonical histones and preferentially binds ~100 bp of linker DNA, which it positively supercoils—opposite to nucleosomes—via DNA-contacting regions in CENP-T and CENP-W (PMID:22304917, PMID:24234442). This chromatin-engaging module is centered over the CENP-B box between flanking CENP-A nucleosomes and assembles with the CENP-A/CENP-B/CENP-C complex over α-satellite DNA (PMID:27384170). The N-terminal disordered region of CENP-T acts as a scaffold for outer kinetochore assembly: it directly binds the Spc24/25 RWD domain of the Ndc80 complex, an interaction strengthened by CDK1:Cyclin B phosphorylation, allowing CENP-T to recruit up to two Ndc80 complexes plus one MIS12-bound Ndc80, thereby providing a pathway parallel to and competitive with CENP-C for KMN network recruitment (PMID:23334297, PMID:28012276, PMID:35165266). Phosphorylation control is layered—CDK regulates KMN recruitment through CENP-T while Aurora B acts through CENP-C—establishing two independently regulated routes to connect chromatin to microtubules (PMID:25660545). CENP-T centromeric deposition is chaperone-dependent, mediated by FACT (Spt16/SSRP1) binding to the CENP-T/W histone fold and by HJURP binding the CENP-T C-terminus, and occurs in S/G2 phase uncoupled from bulk DNA synthesis (PMID:27284163, PMID:30459232). The CENP-T pathway is functionally essential when the Mis12 pathway is compromised, and engineered direct tethering of Ndc80 to CENP-T is sufficient to restore kinetochore-microtubule function and chromosome segregation (PMID:30117803, PMID:35165266). CENP-T function is conserved through divergent lineages, supporting CenH3-independent kinetochore assembly in Lepidoptera (PMID:32032508).

Mechanistic history

Synthesis pass · year-by-year structured walk · 24 steps
  1. 2008 Medium

    Established that CENP-T resides in molecular proximity to core centromere components and loads in a cell-cycle-restricted manner, defining it as a bona fide inner centromere protein.

    Evidence Acceptor-bleaching FRET and FRAP in living human cells

    PMID:19412974

    Open questions at the time
    • Does not resolve whether association is direct or chromatin-mediated
    • No structural basis for CENP-A/CENP-B contacts
  2. 2012 High

    Resolved the chromatin-engaging architecture of CENP-T by showing it forms a histone-like CENP-T-W-S-X heterotetramer that binds and supercoils DNA and is required for kinetochore assembly.

    Evidence Crystal structure, in vitro DNA binding/supercoiling assays, mutagenesis, in vivo kinetochore assembly

    PMID:22304917

    Open questions at the time
    • Did not define how the tetramer is positioned relative to CENP-A nucleosomes in vivo
    • Outer kinetochore linkage not yet mapped
  3. 2012 High

    Identified CENP-T (yeast Cnn1) as a direct centromeric receptor for the Ndc80 complex, sufficient to drive chromosome segregation when artificially tethered.

    Evidence Biochemical binding assays and in vivo chromosome segregation rescue by artificial tethering in budding yeast

    PMID:22561346

    Open questions at the time
    • Structural basis of the Cnn1-Spc24/25 interface not yet solved
    • Regulation of the interaction undefined
  4. 2013 High

    Defined the structural and phospho-regulatory logic of the CENP-T-Ndc80 interaction and showed CENP-T and Mis12 bind Ndc80 mutually exclusively, establishing two parallel recruitment pathways.

    Evidence Crystal structure, biochemical binding and phosphorylation assays, mutagenesis (vertebrate)

    PMID:23334297

    Open questions at the time
    • Did not establish stoichiometry of Ndc80 complexes per CENP-T
    • Full phospho-site map incomplete
  5. 2013 High

    Characterized the DNA-binding preference of the heterotetramer, showing it selects linker over nucleosomal DNA as a (CENP-T-W-S-X)2 unit and induces positive supercoils via CENP-T/CENP-W.

    Evidence In vitro DNA binding/supercoiling assays, mutagenesis, in vivo kinetochore targeting

    PMID:24234442

    Open questions at the time
    • Precise in vivo DNA register relative to CENP-A nucleosomes not resolved
    • Functional role of positive supercoiling untested in vivo
  6. 2013 Medium

    Identified CSN5/JAB1 as a regulator of CENP-T·CENP-W stability and kinetochore recruitment, linking the complex to ubiquitin-proteasome control.

    Evidence Yeast two-hybrid, Co-IP, proteasome inhibitor and ubiquitination assays, immunofluorescence

    PMID:23926101

    Open questions at the time
    • Whether CSN5 acts as ubiquitin ligase adaptor or indirectly is unclear
    • Physiological trigger for degradation undefined
  7. 2015 High

    Dissected the parallel CENP-T and CENP-C pathways, revealing inverted recruitment hierarchies and distinct kinase control (CDK on CENP-T, Aurora B on CENP-C).

    Evidence Ectopic targeting of CENP-C and CENP-T in human cells with epistasis analysis of KMN recruitment

    PMID:25660545

    Open questions at the time
    • Quantitative contribution of each pathway in native centromeres not measured
    • Cross-talk between pathways unresolved
  8. 2015 Medium

    Mapped the dual localization activities of yeast Cnn1 (HFD and N-terminal Ndc80 motif) and showed Mps1 phosphorylation tunes the Ndc80 interaction across the cell cycle.

    Evidence In vivo localization assays, in vitro binding and phosphorylation assays, mutagenesis (budding yeast)

    PMID:25716979

    Open questions at the time
    • Conservation of Mps1 regulation in vertebrates not tested
    • Anaphase-specific behavior basis incomplete
  9. 2015 Medium

    Placed CENP-T downstream of CENP-C and the CENP-A N-tail in centromere assembly hierarchies using two complementary model systems.

    Evidence Genetic suppressor/epistasis analysis in fission yeast and Xenopus egg extract immunodepletion time-courses

    PMID:25569378 PMID:25619765

    Open questions at the time
    • Molecular basis of CENP-C-dependent recruitment not defined
    • Species-specific differences in dependency not reconciled
  10. 2016 Medium

    Identified FACT as the chaperone driving CENP-T/W centromeric deposition independent of DNA replication, defining a loading mechanism.

    Evidence Proteomic screen, reciprocal Co-IP, FRAP, siRNA depletion, ectopic Spt16 targeting

    PMID:27284163

    Open questions at the time
    • Whether FACT acts on free or chromatin-bound CENP-T/W unresolved
    • Coordination with CENP-A loading machinery unclear
  11. 2016 High

    Quantified Ndc80/Mis12 stoichiometry, showing CDK1 phosphorylation of three CENP-T sites enables binding of one MIS12:NDC80 plus two NDC80 complexes, with CENP-C/CENP-T competing for MIS12.

    Evidence Biochemical reconstitution, CDK1:Cyclin B phosphorylation, EM visualization, mutagenesis

    PMID:28012276

    Open questions at the time
    • In vivo confirmation of full stoichiometry at native kinetochores limited
    • Order of assembly events not directly visualized
  12. 2016 Medium

    Demonstrated that CENP-T/W is required during outer kinetochore assembly for stable incorporation of RZZ, Spindly, Mad1/Mad2 and CENP-E, but is dispensable for their maintenance once assembled.

    Evidence Auxin-inducible degron depletion and quantitative kinetochore mass spectrometry

    PMID:26791246

    Open questions at the time
    • Mechanism of stable retention after CENP-T removal unknown
    • Direct vs indirect requirement for each factor not distinguished
  13. 2016 Medium

    Resolved the genomic positioning of CENP-T over the CENP-B box between CENP-A nucleosomes within α-satellite dimers as part of a nuclease-protected CENP-A/B/C/T complex.

    Evidence Base-pair-resolution ChIP-seq, sequential ChIP, nuclease protection

    PMID:27384170

    Open questions at the time
    • Does not establish causal order of complex assembly
    • Generality beyond young α-satellite arrays untested
  14. 2018 Medium

    Identified HJURP as a CENP-T C-terminal binding partner that recruits CENP-T to centromeres during S/G2 phase, coupling CENP-T loading to the CENP-A chaperone.

    Evidence Co-IP, CRISPR knockout, immunofluorescence, domain mapping and binding-deficient mutant

    PMID:30459232

    Open questions at the time
    • Relationship between HJURP- and FACT-dependent loading pathways unresolved
    • Structural basis of HJURP-CENP-T interface not solved
  15. 2018 Medium

    Established functional redundancy and conditional essentiality of the CENP-T Ndc80-recruitment pathway when the Mis12 pathway is impaired.

    Evidence De novo kinetochore assembly in yeast extracts, genetic epistasis, microtubule binding assays

    PMID:30117803

    Open questions at the time
    • Quantitative balance between pathways in normal cells not measured
    • Conservation to metazoa untested in this study
  16. 2020 Medium

    Provided the structural basis for Cnn1-Wip1 (CENP-T/W) recruitment via the Ctf3 complex and proposed feedback regulation of inner kinetochore assembly.

    Evidence High-resolution structure and live-cell imaging (budding yeast)

    PMID:32679099

    Open questions at the time
    • Vertebrate equivalent of Ctf3-mediated recruitment not defined
    • Feedback mechanism only inferred
  17. 2020 Medium

    Revealed a non-canonical role for CENP-T in the meiotic G2/M transition by restraining APC-CDH1 activity to sustain MPF and meiotic resumption in oocytes.

    Evidence siRNA depletion in mouse oocytes with CCNB1/CDH1 rescue and MPF activity assays

    PMID:31964702

    Open questions at the time
    • Direct molecular link between CENP-T and CDH1 regulation unknown
    • Whether this reflects kinetochore or extra-kinetochore function unclear
  18. 2021 Medium

    Demonstrated competitive exclusion at the CENP-T N-terminus, where CDK1 phosphorylation displaces Ccp1 to allow correct mitotic Ndc80 positioning.

    Evidence Co-IP, phospho-mutant analysis, in vitro CDK1 assay, live-cell imaging, segregation assays (fission yeast)

    PMID:34810257

    Open questions at the time
    • Vertebrate orthologs of Ccp1-type competition not identified
    • Full set of N-terminal competitors unknown
  19. 2022 Medium

    Showed two Ndc80 complexes on CENP-T (one direct, one via Mis12) and that direct tethering of both is functionally sufficient for kinetochore-microtubule attachment and cohesion/checkpoint function.

    Evidence DT40 genetics, engineered tethering constructs, segregation and checkpoint assays

    PMID:35165266

    Open questions at the time
    • Why two Ndc80 routes are normally maintained unresolved
    • In vivo geometry of the two Ndc80 complexes not visualized
  20. 2024 Medium

    Defined the multi-interface, dually phospho-regulated CENP-T-Mis12C interaction, refining the molecular logic of the second Ndc80 recruitment route.

    Evidence AlphaFold2 prediction validated by biochemical and DT40 cell biological mutagenesis

    PMID:39628583

    Open questions at the time
    • Predicted interfaces lack experimental structure
    • Temporal ordering of the three interface engagements unknown
  21. 2024 Medium

    Revealed that Ndc80 binding to CENP-T is a two-step maturation process accelerated by molecular clustering, providing a kinetic model for stable attachment.

    Evidence Quantitative in vitro binding and clustering assays, fluorescence microscopy in dividing human cells

    PMID:39700145

    Open questions at the time
    • Molecular nature of binding-site maturation undefined
    • In vivo trigger for clustering-dependent acceleration unclear
  22. 2024 Medium

    Added an Aurora B regulatory input via CENP-W T60 phosphorylation that strengthens CENP-T/W interaction and promotes accurate chromosome alignment.

    Evidence In vitro Aurora B kinase assay, Co-IP, mutagenesis, mitotic alignment assays

    PMID:38200711

    Open questions at the time
    • Structural effect of T60 phosphorylation not resolved
    • Identity of the uncharacterized CENP-T N-terminal contact region unknown
  23. 2025 Medium

    Characterized evolutionary tuning of the CENP-T histone fold domain affecting centromere binding strength and its consequences for gametogenesis.

    Evidence Transgenic mouse model and oocyte microinjection of chimeric CENP-T variants with quantitative binding assays

    PMID:39947176

    Open questions at the time
    • Molecular determinant of altered binding affinity not pinpointed
    • Mechanism linking binding strength to gamete quality unresolved
  24. 2025 Low

    Reported a divergent non-kinetochore role for CENP-T in regulating glutathione synthesis and ferroptosis in renal cell carcinoma via GCLC binding.

    Evidence Co-IP, in vitro GCLC activity assay, domain mapping, ROS and knockdown/overexpression assays

    PMID:40651948

    Open questions at the time
    • Single lab without structural or reconstitution validation
    • Whether this function involves centromeric or soluble CENP-T unclear
    • Generality beyond renal cell carcinoma untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the CENP-T-W-S-X module is positioned and dynamically remodeled within native centromeric chromatin during the cell cycle, and how its multiple phospho-inputs are integrated in vivo, remains incompletely resolved.
  • No high-resolution in vivo structure of the assembled CENP-T complex on native α-satellite chromatin
  • Integration of CDK1, Aurora B and Mps1 phospho-regulation in a single cell-cycle model untested
  • Functional significance of positive DNA supercoiling in vivo unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003677 DNA binding 4 GO:0060090 molecular adaptor activity 4 GO:0005198 structural molecule activity 2
Localization
GO:0005694 chromosome 3 GO:0000228 nuclear chromosome 2
Pathway
R-HSA-1640170 Cell Cycle 3 R-HSA-1474165 Reproduction 2
Partners
CENPCCENPSCENPWCENPXHJURPMIS12NDC80SUPT16H
Complex memberships
CCAN (CENP-A/B/C/T complex)CENP-T-W-S-X heterotetramerkinetochore

Evidence

Reading pass · 29 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2012 CENP-T-W and CENP-S-X complexes coassemble into a stable CENP-T-W-S-X heterotetramer with structural similarity to canonical histones within a nucleosome. The heterotetramer binds and supercoils DNA; mutants compromising heterotetramerization or DNA-protein contacts reduce DNA binding and supercoiling in vitro and compromise kinetochore assembly in vivo. High-resolution structural analysis (crystal structure), in vitro DNA binding and supercoiling assays, site-directed mutagenesis, in vivo kinetochore assembly assays Cell High 22304917
2013 The N-terminal region of vertebrate CENP-T directly interacts with the RWD domain of the Spc24/25 portion of the Ndc80 complex. CDK phosphorylation of CENP-T strengthens a cryptic hydrophobic interaction with Spc25 without direct recognition of the phosphorylated residue. CENP-T and the Mis12 complex bind to the Ndc80 complex via mutually exclusive interactions, supporting two distinct pathways for Ndc80 recruitment to kinetochores. High-resolution structural analysis, biochemical binding assays, phosphorylation assays, mutagenesis The EMBO journal High 23334297
2012 The budding yeast CENP-T ortholog Cnn1 acts as a direct centromere receptor of the Ndc80 complex. The amino terminus of Cnn1 contains a conserved peptide motif that mediates stoichiometric binding to the Spc24-25 domain of Ndc80. Artificial tethering of Ndc80 through Cnn1 allows mini-chromosome segregation in the absence of a natural centromere. Biochemical binding assays, in vivo chromosome segregation assay with artificial tethering Nature cell biology High 22561346
2015 CENP-T and CENP-C act in parallel to recruit the KMN network to kinetochores, but via distinct organizational logic: CENP-T directly interacts with Ndc80, which then promotes KNL1/Mis12 complex recruitment through a separate CENP-T region, inverting the hierarchy relative to the CENP-C pathway. CDK regulates KMN recruitment to CENP-T, while Aurora B promotes KMN recruitment to CENP-C. Ectopic targeting of CENP-C and CENP-T to an ectopic chromosomal locus in human cells; functional epistasis analysis of KMN recruitment Current biology : CB High 25660545
2016 CENP-T is phosphorylated by CDK1:Cyclin B at three distinct sites, enabling binding of one MIS12:NDC80 and two NDC80 complexes. CENP-C and CENP-T together recruit two MIS12 and up to four NDC80 complexes in parallel. Binding of CENP-C and CENP-T to MIS12 is competitive. Electron microscopy of reconstituted complexes supported this stoichiometry model. Biochemical reconstitution, in vitro CDK1:Cyclin B phosphorylation assays, electron microscopy visualization of reconstituted complexes, mutagenesis eLife High 28012276
2013 The CENP-T-W-S-X complex binds preferentially to ~100 bp of linker DNA rather than nucleosome-bound DNA, primarily as a (CENP-T-W-S-X)2 structure, and induces positive DNA supercoils (opposite to canonical nucleosomes). The DNA-binding regions in CENP-T or CENP-W (but not CENP-S or CENP-X) are required for positive supercoiling and kinetochore targeting of the complex. In vitro DNA binding assays, supercoiling assays, mutagenesis, in vivo kinetochore targeting assays Nucleic acids research High 24234442
2016 The histone chaperone FACT (subunits Spt16 and SSRP1) interacts with CENP-T/W; the C-terminal region of Spt16 binds specifically to the histone fold region of CENP-T/W. Depletion of Spt16 impairs CENP-T and CENP-W deposition at endogenous centromeres, and site-directed targeting of Spt16 alone is sufficient to drive local de novo CENP-T accumulation. CENP-T deposition at centromeres is uncoupled from DNA synthesis. Proteomic screen, Co-IP, FRAP, siRNA depletion, site-directed targeting assay Genes & development High 27284163
2013 CSN5/JAB1 directly interacts with both CENP-T and CENP-W (identified by yeast two-hybrid and Co-IP). Ectopically expressed CSN5 promotes ubiquitin- and proteasome-dependent degradation of CENP-T·CENP-W. Formation of the CENP-T·CENP-W complex enhances stability of both proteins, and dysregulation of CSN5 impairs kinetochore recruitment of CENP-T·CENP-W during prophase. Yeast two-hybrid screening, Co-immunoprecipitation, proteasome inhibitor assays, ubiquitination assays, immunofluorescence The Journal of biological chemistry Medium 23926101
2008 CENP-T directly associates with CENP-A and CENP-B at centromeres as shown by FRET in living cells. CENP-T exchange into centromeres is restricted to S-phase of the cell cycle, suggesting a co-replicational loading mechanism. Acceptor-bleaching FRET in living human cells, FRAP Journal of biophotonics Medium 19412974
2016 ChIP-seq and sequential ChIP analyses show that CENPT is centered over the CENPB box between two CENPA nucleosomes on young α-satellite dimers, and interacts with the CENPB/CENPC complex. The entire CENPA/CENPB/CENPC/CENPT complex is nuclease-protected over an α-satellite dimer unit. Comparative ChIP with sequencing (base-pair resolution), sequential ChIP, nuclease protection assay Genome research Medium 27384170
2015 In fission yeast, alteration of the CENP-A (Cnp1) N-tail specifically reduces localization of Cnp20/CENP-T (but not CENP-C) to centromeres, and overexpression of Cnp20/CENP-T suppresses centromere inactivation defects of N-tail mutants, placing CENP-T downstream of CENP-A N-tail in the epigenetic stability pathway. Genetic suppressor analysis, fluorescence microscopy, epistasis (double mutant analysis) Current biology : CB Medium 25619765
2015 The budding yeast Cnn1 (CENP-T ortholog) has two kinetochore localization activities: a C-terminal histone-fold domain (HFD) that associates with the centromere region, and an N-terminal Spc24/Spc25 interaction sequence (residues 25-91) that mediates linkage to Ndc80. Mps1 kinase phosphorylates Cnn1-S74 in vitro to modulate the Cnn1-Ndc80 interaction; from G1 through metaphase, Cnn1 uses both localization activities, while at anaphase onset (when Mps1 activity decreases) enrichment is mainly via the N-terminal Spc24/25 interaction. In vivo cell biology (localization assays), in vitro binding assays, phosphorylation assays, mutagenesis Genetics Medium 25716979
2015 In Xenopus egg extracts, CENP-T centromeric recruitment occurs in late interphase (after CENP-C but before CENP-W), is dependent on CENP-C (depletion reduces CENP-T levels at centromeres), but CENP-T does not participate in CENP-A deposition. CENP-T plays a major role in kinetochore assembly; its depletion reduces Ndc80 and Mis12 recruitment. Xenopus egg extract cell-free system, immunodepletion, immunofluorescence, time-course analysis Nucleus (Austin, Tex.) Medium 25569378
2018 CENP-T directly binds Holliday junction recognition protein (HJURP), a chaperone for CENP-A loading; the binding interface was mapped to the C terminus of CENP-T. HJURP knockout by CRISPR minimized CENP-T recruitment to centromeres. HJURP recruits CENP-T to centromeres during S/G2 phase. A HJURP-binding-deficient CENP-T mutant (CENP-T6L) failed to localize to centromeres. Co-IP, CRISPR knockout, immunofluorescence, mutagenesis (domain mapping and binding-deficient mutant) The Journal of biological chemistry Medium 30459232
2018 In budding yeast, the CENP-T (Cnn1) pathway for Ndc80 recruitment becomes essential for viability when the Mis12 pathway is compromised by Dsn1 phosphorylation defects, demonstrating genetic epistasis and redundancy between the two Ndc80 recruitment pathways. De novo kinetochore assembly assay in yeast extracts, genetic epistasis analysis (double mutant), microtubule binding assay eLife Medium 30117803
2020 The budding yeast Cnn1-Wip1 (CENP-T/W) heterodimer structure was determined at high resolution bound to the Ctf3 complex. Live-cell imaging experiments provided a mechanism for Ctf3c and Cnn1-Wip1 recruitment to the kinetochore, suggesting feedback regulation of Ctf19c assembly. High-resolution crystal/cryo structure, live-cell imaging Current biology : CB Medium 32679099
2020 In Lepidoptera (CenH3-deficient organisms), a divergent CENP-T homolog is required for accurate mitotic progression and is sufficient to recruit Mis12 and Ndc80 outer kinetochore complexes. CRISPR-mediated knockout of CENP-T in Bombyx mori establishes an essential in vivo function. CENP-T-based kinetochore assembly functions independently of CenH3 in these insects. CRISPR-mediated gene editing (Bombyx mori), mass spectrometry (kinetochore composition), Co-IP (Mis12/Ndc80 recruitment), functional rescue assay Current biology : CB Medium 32032508
2016 In mitotic CENP-T/W-depleted cells (using auxin-inducible degron approach), stripping of CENP-T from chromosomes in early mitosis reveals the RZZ complex (Rod-Zw10-zwilch), Spindly, Mad1/Mad2, and CENP-E require CENP-T/W function during kinetochore assembly for stable outer kinetochore association, but once assembled, remain associated after CENP-T stripping during mitosis. Auxin-inducible degron (AID) system, quantitative kinetochore proteomics (mass spectrometry of mitotic chromosomes), comparison with conventional knockouts Open biology Medium 26791246
2022 Two copies of Ndc80C exist on CENP-T: one via direct binding and one via Mis12C. Cells lacking both CENP-T-Mis12C and CENP-C-Mis12C interactions show defects in sister chromatid cohesion and spindle checkpoint protein recruitment. Artificial direct tethering of two Ndc80C to CENP-T restores proper kinetochore-microtubule interactions without requiring direct Mis12C-Ndc80C binding, demonstrating that N-N on CENP-T is functionally sufficient. DT40 cell genetics, artificial engineering/tethering constructs, cell biology assays (chromosome segregation, spindle checkpoint) Nature communications Medium 35165266
2021 In fission yeast, Ccp1 directly interacts with CENP-T via a Ccp1-interaction motif (CIM) at the N terminus of CENP-T, adjacent to the Ndc80 receptor motif. CDK1 phosphorylation of the CIM domain weakens Ccp1 interaction, causing Ccp1 to dissociate from centromeres in mitosis. Phospho-null CIM mutant retains Ccp1 at centromeres during mitosis and disrupts Ndc80 positioning, causing chromosome missegregation, demonstrating competitive exclusion between Ccp1 and Ndc80 at the CENP-T N terminus. Co-IP, mutagenesis (phosphomimetic and phospho-null mutants), in vitro CDK1 kinase assay, live-cell imaging, chromosome segregation assay Proceedings of the National Academy of Sciences of the United States of America Medium 34810257
2024 CENP-T-Mis12C interaction involves three binding surfaces (identified by AlphaFold2 predictions combined with cell biological and biochemical analyses), and is cooperatively regulated by dual phosphorylation of Dsn1 (Mis12C component) and CENP-T. Each interface is important for Mis12C recruitment to CENP-T in cells. AlphaFold2 structure prediction validated by biochemical binding assays and cell biology (DT40 cells lacking CENP-C-Mis12C interaction), mutagenesis iScience Medium 39628583
2024 Ndc80 binding to CENP-T is a two-step process: initial rapid association/dissociation from disordered N-terminal sites, followed by binding site maturation resulting in stronger Ndc80 retention. Within CENP-T clusters (high molecular density), maturation is markedly accelerated compared to soluble CENP-T monomers. The two Ndc80 binding sites in human CENP-T exhibit distinct maturation rates correlating with differences in amino acid content. Quantitative in vitro binding assays, molecular clustering assays, fluorescence microscopy in dividing human cells Proceedings of the National Academy of Sciences of the United States of America Medium 39700145
2024 Aurora B phosphorylates CENP-W at threonine 60, which enhances the interaction between CENP-W and the histone fold domain and an uncharacterized N-terminal region of CENP-T, promoting robust metaphase chromosome alignment and accurate chromosome segregation. In vitro Aurora B kinase assay, Co-IP, mutagenesis, chromosome alignment assays in mitosis Journal of molecular cell biology Medium 38200711
2020 In mouse oocytes, depletion of CENP-T by siRNA increases CDH1 (FZR1) levels, leading to increased APC-CDH1 activity, decreased CCNB1 levels, attenuated MPF activity, and severely compromised meiotic resumption. This defect is rescued by CCNB1 overexpression or CDH1 knockdown, placing CENP-T upstream of CDH1/APC-CDH1 in the meiotic G2/M transition pathway. siRNA injection in mouse oocytes, Western blot, rescue experiments (overexpression and siRNA knockdown), MPF activity assay Journal of cell science Medium 31964702
2015 CENP-T C-terminus is specifically proximal to H3.1 (but not H3.2, H3.3, or H3.1 mutants C96A and C110A) at centromeres, as shown by in vivo FRET, suggesting that CENP-T bridges a CENP-A-containing and an H3.1-containing nucleosome at centromeres. In vivo acceptor-bleaching FRET in human cells International journal of molecular sciences Low 25775162
2025 CENPT interacts with γ-glutamyl-cysteine ligase catalytic subunit (GCLC) by directly binding to GCLC residues 213-424, competitively displacing GCLM, and increasing GCLC catalytic activity, thereby promoting glutathione synthesis and inhibiting ferroptosis in renal cell carcinoma cells. GSH in turn increases CENPT expression via ATF2-mediated transcriptional regulation, forming a feedback loop. Co-IP, in vitro GCLC activity assay, domain mapping, ROS assay, knockdown/overexpression Cell death & disease Low 40651948
2025 Cryo-EM structures of CCAN bound to free DNA and monomeric/dimeric CENP-A nucleosomes show that the CENP-T-W-S-X (TWSX) module engages 65-70 bp of DNA including 30-35 bp of an upstream α-satellite repeat in a manner resembling nucleosome DNA wrapping. On a dimeric α-satellite array, CCAN accommodation requires unwrapping of DNA from the TWSX module and 25 bp from the upstream nucleosome. Cryo-EM structure determination of CCAN complexes with DNA and CENP-A nucleosomes bioRxivpreprint Medium
2025 Lepidopteran CENP-T forms a stable monomer due to a structural rearrangement repositioning HFD helix α3, bringing a conserved two-helical extension to take over the role of CENP-W partner. This change does not affect DNA-binding ability of lepidopteran CENP-T. Structural analysis, biochemical solubility/stability assays, DNA binding assays EMBO reports Medium 41162737
2025 Adaptive evolution of the histone fold domain of mouse CENP-T reduced centromere binding. Chimeric CENP-T variants with HFD from closely related species showed increased centromere binding when expressed in mouse oocytes or in a transgenic mouse model, and this adaptation supports robust female gametogenesis. This effect was independent of specific centromeric DNA sequence. Transgenic mouse model, oocyte microinjection of chimeric CENP-T variants, quantitative centromere binding assays Current biology : CB Medium 39947176

Source papers

Stage 0 corpus · 33 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2012 CENP-T-W-S-X forms a unique centromeric chromatin structure with a histone-like fold. Cell 208 22304917
2013 CENP-T provides a structural platform for outer kinetochore assembly. The EMBO journal 171 23334297
2012 CENP-T proteins are conserved centromere receptors of the Ndc80 complex. Nature cell biology 152 22561346
2015 Distinct organization and regulation of the outer kinetochore KMN network downstream of CENP-C and CENP-T. Current biology : CB 116 25660545
2016 Molecular basis of outer kinetochore assembly on CENP-T. eLife 109 28012276
2017 Integrity of the human centromere DNA repeats is protected by CENP-A, CENP-C, and CENP-T. Proceedings of the National Academy of Sciences of the United States of America 96 28167779
2013 The centromeric nucleosome-like CENP-T-W-S-X complex induces positive supercoils into DNA. Nucleic acids research 65 24234442
2020 CenH3-Independent Kinetochore Assembly in Lepidoptera Requires CCAN, Including CENP-T. Current biology : CB 52 32032508
2018 An assay for de novo kinetochore assembly reveals a key role for the CENP-T pathway in budding yeast. eLife 52 30117803
2016 The CENP-T/-W complex is a binding partner of the histone chaperone FACT. Genes & development 47 27284163
2016 CENPT bridges adjacent CENPA nucleosomes on young human α-satellite dimers. Genome research 38 27384170
2015 The CENP-A N-tail confers epigenetic stability to centromeres via the CENP-T branch of the CCAN in fission yeast. Current biology : CB 38 25619765
2008 Live-cell imaging reveals sustained centromere binding of CENP-T via CENP-A and CENP-B. Journal of biophotonics 26 19412974
2022 Recruitment of two Ndc80 complexes via the CENP-T pathway is sufficient for kinetochore functions. Nature communications 25 35165266
2016 Auxin/AID versus conventional knockouts: distinguishing the roles of CENP-T/W in mitotic kinetochore assembly and stability. Open biology 20 26791246
2015 The distinct functions of CENP-C and CENP-T/W in centromere propagation and function in Xenopus egg extracts. Nucleus (Austin, Tex.) 19 25569378
2020 The Structural Basis for Kinetochore Stabilization by Cnn1/CENP-T. Current biology : CB 16 32679099
2013 CSN5/JAB1 interacts with the centromeric components CENP-T and CENP-W and regulates their proteasome-mediated degradation. The Journal of biological chemistry 15 23926101
2015 The Mps1 kinase modulates the recruitment and activity of Cnn1(CENP-T) at Saccharomyces cerevisiae kinetochores. Genetics 14 25716979
2018 Holliday junction recognition protein interacts with and specifies the centromeric assembly of CENP-T. The Journal of biological chemistry 10 30459232
2017 A defect in the inner kinetochore protein CENPT causes a new syndrome of severe growth failure. PloS one 10 29228025
2020 CENP-T regulates both the G2/M transition and anaphase entry by acting through CDH1 in meiotic oocytes. Journal of cell science 7 31964702
2025 Adaptive evolution of CENP-T modulates centromere binding. Current biology : CB 6 39947176
2025 CENPT prevents renal cell carcinoma against ferroptosis by enhancing the synthesis of glutathione. Cell death & disease 6 40651948
2021 Ccp1-Ndc80 switch at the N terminus of CENP-T regulates kinetochore assembly. Proceedings of the National Academy of Sciences of the United States of America 4 34810257
2015 The CENP-T C-terminus is exclusively proximal to H3.1 and not to H3.2 or H3.3. International journal of molecular sciences 4 25775162
2024 Molecular details and phosphoregulation of the CENP-T-Mis12 complex interaction during mitosis in DT40 cells. iScience 2 39628583
2024 Binding site maturation modulated by molecular density underlies Ndc80 binding to kinetochore receptor CENP-T. Proceedings of the National Academy of Sciences of the United States of America 2 39700145
2024 Aurora B promotes the CENP-T-CENP-W interaction to guide accurate chromosome segregation in mitosis. Journal of molecular cell biology 1 38200711
2024 Binding Site Maturation Modulated by Molecular Density Underlies Ndc80 Binding to Kinetochore Receptor CENP-T. bioRxiv : the preprint server for biology 1 38464265
2025 Insects evolved a monomeric histone-fold domain in the CENP-T protein family. EMBO reports 0 41162737
2025 Fused in Sarcoma (FUS) promotes renal cell carcinoma progression via the KCMF1/FUS/CENPT axis and activation of the JNK signaling pathway. Journal of translational medicine 0 41184988
2023 Bioinformatics insights into CENP-T and CENP-W protein-protein interaction disruptive amino acid substitution in the CENP-T-W complex. Journal of cellular biochemistry 0 37943107

Missed literature

Know a paper Affinage missed for CENPT? Flag it for the maintainers and the community.

No submissions yet.