Affinage

CENPF

Centromere protein F · UniProt P49454

Length
3114 aa
Mass
357.5 kDa
Annotated
2026-06-09
100 papers in source corpus 38 papers cited in narrative 38 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-F is a large, cell-cycle-regulated nuclear matrix protein that functions as a multivalent microtubule-associated scaffold, accumulating during S/G2 and peaking at G2/M before being rapidly degraded after mitosis (PMID:7542657). Its mitotic role centers on the outer kinetochore: it loads onto kinetochores from late G2 through early anaphase downstream of constitutive and checkpoint components, requiring CENP-I and BUB1, with which it forms a direct, biochemically reconstituted complex via a CENP-F coiled-coil and the BUB1 kinase domain (PMID:7904902, PMID:15020684, PMID:12640463, PMID:29748388). A separate C-terminal interface engages the nucleoporin Nup133 to drive nuclear-envelope/pore localization in prophase, while the adjacent BUB1-binding element targets the kinetochore-core domain (PMID:29632243). At kinetochores CENP-F serves as a recruitment hub, linking the Ndel1/Nde1/Lis1/dynein pathway and CLASP to the kinetochore and thereby stabilizing kinetochore-microtubule attachments, building tension, limiting Nde1-dependent dynein stripping of corona cargoes, and supporting biorientation (PMID:15854912, PMID:17600710, PMID:32207772). CENP-F binds microtubules directly through two domains at opposite ends of the molecule, the C-terminal of which stimulates microtubule polymerization in vitro, and it can track growing and shrinking microtubule tips to transport cargo (PMID:16601978, PMID:23892111, PMID:28701340). Its activity extends beyond mitosis: CENP-F regulates centrosomal microtubule nucleation via Hook2, transports mitochondria through a cell-cycle-dependent interaction with Miro, links the SNARE machinery (syntaxin 4/SNAP-25/VAMP2) to microtubule-based vesicular transport, and governs interphase microtubule dynamics underlying migration, focal adhesion turnover, and ciliogenesis (PMID:19793914, PMID:18827011, PMID:26259702, PMID:27146114). CENP-F is farnesylated at its C-terminal CAAX box, a modification required for nuclear-envelope and kinetochore targeting and for post-mitotic degradation (PMID:10852915, PMID:12154071), and its abundance is controlled both by ubiquitin-proteasome turnover counteracted by the deubiquitinase USP4 and by periodic SETDB1-PC4-UPF1-mediated CENPF mRNA degradation (PMID:39922805, PMID:40016337). Loss of CENP-F causes dilated cardiomyopathy in mice and a human ciliopathy (Strømme syndrome) (PMID:22563055, PMID:25564561).

Mechanistic history

Synthesis pass · year-by-year structured walk · 19 steps
  1. 1993 High

    Established that CENP-F is a bona fide kinetochore-associated protein whose binding and release are coupled to mitotic progression rather than to microtubule presence.

    Evidence Affinity-purified antibody immunofluorescence and immunodepletion in HeLa cells

    PMID:7904902

    Open questions at the time
    • Molecular determinant of kinetochore binding unknown
    • No information on cell-cycle regulation of abundance
  2. 1995 High

    Defined CENP-F's molecular architecture and cell-cycle dynamics, showing it is a coiled-coil nuclear matrix protein peaking at G2/M and degraded after mitosis.

    Evidence cDNA cloning, IF across the cell cycle, immunoelectron microscopy, and biochemical fractionation

    PMID:7542657

    Open questions at the time
    • Function of predicted P-loop motif never validated
    • Mechanism of post-mitotic degradation not addressed
  3. 2002 High

    Showed CENP-F is farnesylated and that this lipid modification is required for nuclear-envelope/kinetochore targeting and post-mitotic turnover, defining a regulatory handle exploited by farnesyl transferase inhibitors.

    Evidence In vitro farnesyl transferase assays, metabolic labeling, FTI treatment, and CAAX mutagenesis with localization readouts

    PMID:10852915 PMID:12154071

    Open questions at the time
    • How farnesylation mechanistically promotes membrane/kinetochore targeting unresolved
    • Mouse work later showed farnesylated C-terminus dispensable for development
  4. 2004 High

    Placed CENP-F in a hierarchical kinetochore assembly pathway, showing its recruitment depends on constitutive (CENP-I) and checkpoint (Bub1) components.

    Evidence RNAi depletion of CENP-I and Bub1 with IF localization readouts of CENP-F

    PMID:12640463 PMID:15020684

    Open questions at the time
    • Direct versus indirect recruitment not distinguished at this stage
    • Binding interface not mapped
  5. 2006 High

    Demonstrated that CENP-F maintains kinetochore-microtubule attachment stability, sister tension, and checkpoint integrity, and is itself a direct microtubule-binding protein with polymerization-stimulating activity.

    Evidence RNAi with live-cell Mad1 imaging and inter-kinetochore measurements, plus in vitro MT binding/polymerization assays with purified domains

    PMID:16219694 PMID:16252009 PMID:16601978

    Open questions at the time
    • Structural basis of MT binding not resolved
    • Relative contributions of two MT-binding domains unclear
  6. 2007 High

    Identified CENP-F as the recruitment hub linking the Ndel1/Nde1/Lis1/dynein motor pathway to kinetochores via direct interaction.

    Evidence Co-IP and reciprocal RNAi epistasis with localization readouts

    PMID:17600710

    Open questions at the time
    • Binding interface for Nde1/Ndel1 not mapped at residue level here
  7. 2009 High

    Extended CENP-F function to the centrosome, showing it controls centrosomal (but not Golgi) microtubule nucleation through Hook2.

    Evidence Y2H and co-IP plus MT repolymerization assays in CENP-F(-/-) MEFs

    PMID:19793914

    Open questions at the time
    • Mechanism by which CENP-F-Hook2 promotes nucleation/anchoring unresolved
  8. 2013 High

    Resolved the distinct microtubule-binding properties of CENP-F's two domains, showing the N-terminal domain binds with Ndc80-like affinity in a disordered geometry consistent with initial lateral attachment.

    Evidence Cosedimentation assays and electron microscopy of domain-microtubule complexes

    PMID:23892111

    Open questions at the time
    • In vivo relevance of disordered binding geometry untested
    • Single lab
  9. 2018 High

    Defined the molecular specificity of CENP-F kinetochore recruitment, reconstituting a direct CENP-F coiled-coil/BUB1 kinase-domain interaction and separating Nup133 and BUB1 binding interfaces.

    Evidence Biochemical reconstitution and structure-guided mutagenesis with RNAi/localization readouts

    PMID:29632243 PMID:29748388

    Open questions at the time
    • Whether BUB1 kinase activity is required for binding unclear
    • CENP-E redundancy in recruitment not fully quantified
  10. 2020 High

    Used separation-of-function mutants to assign discrete kinetochore activities, showing MT-binding domains stabilize attachments and transduce force while a distinct Nde1-binding domain limits dynein-mediated corona stripping.

    Evidence CRISPR-engineered mutants, live-cell imaging, quantitative attachment analysis, and co-IP

    PMID:32207772

    Open questions at the time
    • How CENP-F-Nde1 antagonizes dynein mechanistically not fully resolved
  11. 2017 High

    Explained the spatial control of CENP-F's dual nuclear/cytoplasmic life, showing Cdk1 phosphorylation of its bipartite NLS weakens karyopherin-alpha binding to drive G2 nuclear export, and that CENP-F tracks dynamic microtubule tips to transport cargo.

    Evidence NLS phosphosite mutagenesis with karyopherin-alpha binding assays, plus in vitro tip-tracking reconstitution and live imaging

    PMID:28701340 PMID:28723232

    Open questions at the time
    • Identity of export receptor downstream of NLS phospho-regulation not defined
    • How tip-tracking is mechanically achieved unresolved
  12. 2015 High

    Established CENP-F's non-mitotic transport role, showing a cell-cycle-dependent Miro interaction recruits it to mitochondria to drive peripheral mitochondrial spreading at cytokinesis.

    Evidence Co-IP, live imaging, and RNAi with quantitative mitochondrial distribution analysis

    PMID:26259702

    Open questions at the time
    • Coupling between Miro recruitment and tip-tracking not directly demonstrated
  13. 2008 High

    Linked CENP-F to vesicular transport by showing it bridges the SNARE machinery to microtubules and supports GLUT4 trafficking.

    Evidence Y2H, co-IP of endogenous syntaxin 4/SNAP-25/VAMP2, RNAi, and GLUT4 trafficking assays

    PMID:18827011

    Open questions at the time
    • Direct binding interface with syntaxin 4 not mapped
    • Generalizability beyond GLUT4 cargo untested
  14. 2016 High

    Demonstrated that CENP-F broadly governs interphase microtubule dynamics underlying migration, focal adhesion turnover, and ciliogenesis, expanding its role beyond mitosis.

    Evidence CENP-F(-/-) MEFs with live MT-dynamics imaging and functional assays

    PMID:27146114

    Open questions at the time
    • Molecular mechanism connecting CENP-F to MT dynamics not pinpointed
  15. 2023 High

    Refined the conserved kinetochore module, showing BUB-1/HCP-1/2/CLS-2 (the BHC module) synergistically stabilize microtubules and promote pause, meaning CENP-F orthologs actively control MT dynamics rather than merely targeting CLASP.

    Evidence In vitro MT stabilization/pause assays plus in vivo structure-function in C. elegans (building on earlier CLASP-targeting work)

    PMID:15854912 PMID:36799894

    Open questions at the time
    • Direct extrapolation of synergistic activity to human CENP-F kinetochores untested
  16. 2025 Medium

    Defined how CENP-F abundance is set, identifying USP4-mediated deubiquitination as a stabilizer, SETDB1-PC4-UPF1 as a periodic mRNA-degradation machine, and importin-beta/microtubule integrity as controllers of mitotic localization and timed degradation.

    Evidence Co-IP/ubiquitination assays, RNA-IP and mRNA stability assays, and proximity ligation with overexpression/MT-depolymerization experiments

    PMID:39922805 PMID:40016337 PMID:40596417

    Open questions at the time
    • E3 ligase for CENP-F not identified in these findings
    • Importin-beta link rests on proximity ligation rather than classical co-IP
  17. 2012 High

    Provided in vivo disease relevance, showing cardiac-specific CENP-F deletion causes fully penetrant dilated cardiomyopathy with microtubule and intercalated-disc disruption.

    Evidence Cre-loxP conditional knockout in cardiomyocytes with histology, IF, and cardiac functional analysis

    PMID:22563055

    Open questions at the time
    • Whether cardiomyopathy stems from mitotic versus interphase MT defects not resolved
  18. 2015 Medium

    Connected CENP-F to human ciliopathy, showing it localizes to mother-centriole subdistal appendages, co-IPs with IFT88, and that CENPF mutations cause truncated cilia (Strømme syndrome).

    Evidence Whole exome sequencing, co-IP with IFT88, IF co-localization, and patient tissue analysis

    PMID:25564561

    Open questions at the time
    • Mechanism linking CENP-F to IFT-dependent ciliogenesis unresolved
    • Single lab
  19. 2024 Medium

    Revealed a nuclear transcriptional role, showing CENP-F co-regulates G2/M gene expression with FOXM1 by supporting chromatin accessibility and FOXM1-MBB complex formation in a cancer-specific manner.

    Evidence CRISPR loss-of-function with ATAC-seq, ChIP, and FOXM1-MBB co-IP

    PMID:38779933

    Open questions at the time
    • How a kinetochore/MT protein acts in transcription mechanistically unclear
    • Single lab

Open questions

Synthesis pass · forward-looking unresolved questions
  • How CENP-F's many spatially distinct activities — kinetochore scaffolding, tip-tracking cargo transport, centrosomal nucleation, and transcriptional co-regulation — are coordinated by a single molecule, and which E3 ligase drives its post-mitotic destruction, remains unresolved.
  • E3 ubiquitin ligase for CENP-F not identified in the corpus
  • No integrated structural model of the full-length protein
  • Mechanistic basis of cancer-specific transcriptional role unestablished

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008092 cytoskeletal protein binding 3 GO:0060090 molecular adaptor activity 3
Localization
GO:0005856 cytoskeleton 4 GO:0000228 nuclear chromosome 2 GO:0005635 nuclear envelope 2 GO:0005815 microtubule organizing center 2 GO:0005634 nucleus 1
Pathway
R-HSA-1640170 Cell Cycle 4 R-HSA-1852241 Organelle biogenesis and maintenance 3 R-HSA-5653656 Vesicle-mediated transport 3
Complex memberships
FOXM1-MBB complexNdel1/Nde1/Lis1/dynein pathwaykinetochoresyntaxin 4/SNAP-25/VAMP2 SNARE complex

Evidence

Reading pass · 38 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1995 CENP-F is a nuclear matrix protein that accumulates during the cell cycle, peaks at G2/M, localizes to kinetochore plates (outer surface of outer kinetochore plate) from late G2 through early anaphase, then redistributes to the spindle midzone and midbody, and is rapidly degraded after mitosis. The predicted structure consists of two ~1,600-amino acid coiled-coil domains flanking a central flexible core, with a putative P-loop nucleotide binding site (ADIPTGKT) in the globular C-terminus. cDNA cloning, immunofluorescence across cell cycle stages, immunoelectron microscopy, nuclease digestion, cell fractionation The Journal of cell biology High 7542657
1993 CENP-F associates with kinetochores independent of tubulin, and its dissociation from kinetochores is dependent on events connected with the onset of anaphase. CENP-F localizes to the outer surface of the outer kinetochore plate. Immunofluorescence with affinity-purified antibodies, immune depletion experiments, indirect immunofluorescence on HeLa cells Cell motility and the cytoskeleton High 7904902
2000 CENP-F is farnesylated in tumor cells (DLD-1): peptides from the COOH-terminal CAAX box of CENP-F are substrates for farnesyl transferase but not geranylgeranyl transferase-I, and prenylation is completely inhibited by the farnesyl transferase inhibitor SCH 66336. Preventing farnesylation does not affect kinetochore localization of CENP-F but alters the association between CENP-E and microtubules. In vitro farnesyl transferase substrate assay, metabolic labeling in DLD-1 cells, immunohistochemistry with FTI treatment The Journal of biological chemistry High 10852915
2002 Farnesylation of CENP-F is required for its localization to the nuclear envelope at G2/M and to kinetochores in prometaphase, for timely G2/M progression, and for CENP-F degradation after mitosis. Ectopic expression of the kinetochore targeting domain delays G2/M progression in a CAAX motif-dependent manner. Ectopic expression of CENP-F kinetochore targeting domain with CAAX mutation, farnesyl transferase inhibitor treatment, immunofluorescence localization, cell cycle analysis Journal of cell science High 12154071
1998 CENP-F directly interacts with CENP-E (via yeast two-hybrid using CENP-E kinetochore binding domain as bait) and assembles onto kinetochores sequentially after CENP-E. CENP-F, BubR1, and CENP-E define discrete steps along the kinetochore assembly pathway. Yeast two-hybrid screen using CENP-E kinetochore binding domain, immunofluorescence co-localization, sequential kinetochore assembly analysis The Journal of cell biology Medium 9763420
2004 Bub1 is required for kinetochore localization of CENP-F (as well as BubR1, Cenp-E, and Mad2) in human somatic cells; RNAi-mediated depletion of Bub1 prevents subsequent CENP-F kinetochore assembly. RNA interference (RNAi) depletion of Bub1 in human cells, immunofluorescence to assess kinetochore localization of CENP-F and other checkpoint proteins Journal of cell science High 15020684
2003 CENP-I (a constitutive kinetochore protein) is required for kinetochore localization of CENP-F and checkpoint proteins MAD1 and MAD2; depletion of CENP-I causes G2 delay and prevents mitotic arrest. RNAi depletion of CENP-I, immunofluorescence for CENP-F and checkpoint protein localization, cell cycle analysis Nature cell biology High 12640463
2005 In C. elegans, HCP-1/2 (CENP-F orthologs) physically associate with CLASP (CLS-2) and are required for its kinetochore localization; CLASP depletion does not prevent HCP-1/2 targeting. The key role of HCP-1/2 is to target CLASP to kinetochores to promote microtubule polymerization at kinetochore-bound microtubules and ensure sister-chromatid biorientation. Biochemical purification, co-immunoprecipitation, RNAi depletion, immunofluorescence localization in C. elegans embryos, genetic epistasis Current biology : CB High 15854912
2005 CENP-F depletion by RNAi causes reduced stability of kinetochore microtubules, reduced tension between sister kinetochores of aligned chromosomes, merotelic associations, and continuous or intermittent Mad1 recruitment ('twinkling') indicating cycles of spindle checkpoint reactivation and silencing. A subset of CENP-F-depleted cells show complete failure of kinetochore assembly. RNAi depletion, live-cell imaging with YFP-Mad1, inter-kinetochore distance measurements, immunofluorescence The EMBO journal High 16252009
2005 CENP-F RNAi causes failure of metaphase chromosome alignment, anaphase segregation, and cytokinesis; kinetochores can still attach microtubules but oscillatory movements and inter-kinetochore distances are severely reduced. CENP-F depletion also causes premature loss of centromeric chromatid cohesion. The prolonged mitosis induced by CENP-F RNAi is dependent on the spindle checkpoint kinase BubR1. RNAi, immunofluorescence, live-cell imaging, epistasis with BubR1 RNAi Journal of cell science High 16219694
2006 CENP-F is a novel microtubule-binding protein with two microtubule-binding domains at opposite ends of the molecule; the C-terminal microtubule-binding domain stimulates microtubule polymerization in vitro. CENP-F depletion causes cells to exit mitosis despite defective kinetochore attachments and reduces kinetochore levels of Mad1, Mad2, hBUBR1, hBUB1, and hMps1. In vitro microtubule binding and polymerization assays with purified CENP-F domains, RNAi depletion, immunofluorescence quantification of checkpoint proteins Chromosoma High 16601978
2007 CENP-F directly interacts with Ndel1 and Nde1 (NudE-related proteins), and is required for kinetochore localization of Ndel1, Nde1, and Lis1. Nde1 (but not Ndel1) is required for kinetochore localization of dynein. CENP-F thus links the Ndel1/Nde1/Lis1/dynein pathway to kinetochores. Co-immunoprecipitation, RNAi depletion of CENP-F, Nde1, and Ndel1, immunofluorescence for localization, chromosome alignment assays Current biology : CB High 17600710
2009 CENP-F localizes to the centrosome and interacts with Hook2 (a centrosomal linker protein) via yeast two-hybrid and co-immunoprecipitation. Loss of CENP-F in CENP-F(-/-) cells eliminates centrosome-specific microtubule repolymerization after nocodazole treatment, but MT repolymerization from the Golgi is unaffected, indicating CENP-F regulates centrosomal MT nucleation and anchoring. Yeast two-hybrid screen, co-immunoprecipitation, CENP-F(-/-) MEFs, microtubule repolymerization assay after nocodazole washout, immunofluorescence Molecular biology of the cell High 19793914
2008 Murine CENP-F interacts with syntaxin 4 (a SNARE complex component) via yeast two-hybrid and co-immunoprecipitation. Endogenous CENP-F forms a complex with syntaxin 4, SNAP-25, and VAMP2. CENP-F depletion disrupts GLUT4 trafficking, and dominant-negative CENP-F inhibits cell coupling, demonstrating a role in vesicular transport through linking the SNARE system to the microtubule network. Yeast two-hybrid, co-immunoprecipitation, confocal colocalization, RNAi depletion, dominant-negative expression, GLUT4 trafficking assay Journal of cell science High 18827011
2013 The N-terminal microtubule-binding domain of CENP-F binds microtubules with affinity similar to the Ndc80 complex, while the C-terminal domain shows much lower affinity. EM analysis reveals both domains engage the microtubule surface in a disordered manner with no favored binding geometry, suggesting they may facilitate initial lateral attachments. Biochemical microtubule binding assays (cosedimentation), electron microscopy of domain-microtubule complexes Journal of molecular biology High 23892111
2015 CENP-F interacts directly with the mitochondrial protein Miro in a cell cycle-dependent manner. Cenp-F is recruited to mitochondria by Miro at the time of cytokinesis and associates with microtubule growing tips. Loss of CENP-F or Miro decreases spreading of the mitochondrial network and causes cytokinesis-specific defects in mitochondrial transport toward the cell periphery. Co-immunoprecipitation, live-cell imaging, RNAi depletion of CENP-F and Miro, quantitative mitochondrial distribution analysis Nature communications High 26259702
2017 CENP-F tracks growing microtubule ends in living cells. In vitro reconstitution demonstrates that microtubule tips can transport CENP-F-coated artificial cargoes over micrometer-long distances during both growing and shrinking phases, establishing CENP-F as a tip-tracking transporter for mitochondria and other cargoes. Live-cell imaging of CENP-F tracking, in vitro reconstitution assay with CENP-F-coated beads and dynamic microtubules Molecular biology of the cell High 28701340
2017 CENP-F contains a bipartite classical nuclear localization signal (cNLS) with three Cdk1 phosphorylation sites. Phosphomimetic mutations at these sites strongly reduce the interaction between the CENP-F cNLS and karyopherin α (importin α), and diminish nuclear localization. Cdk1-mediated phosphorylation of the cNLS in G2 phase thus regulates CENP-F nuclear export, enabling its cytoplasmic functions. Identification and mutagenesis of cNLS phosphorylation sites, binding assay between cNLS peptides and karyopherin α, cell localization assay with phosphomimetic mutants Cell cycle (Georgetown, Tex.) High 28723232
2018 CENP-F directly and specifically interacts with BUB1 (but not BUBR1), whereas CENP-E directly interacts with BUBR1 (but not BUB1). The CENP-F/BUB1 interaction requires a dimeric coiled-coil in CENP-F and the kinase domain of BUB1, established by biochemical reconstitution. BUB1 is stringently required for CENP-F kinetochore localization while BUBR1 is dispensable for CENP-E localization. Both are recruited to kinetochores independently of the RZZ complex. Biochemical reconstitution of direct interactions, mutagenesis of binding determinants, RNAi depletion of BUB1/BUBR1 with immunofluorescence localization readout The Journal of biological chemistry High 29748388
2018 The Cenp-F C-terminal region contains separate binding sites for Nup133 and Bub1. Nup133 interacts with a conserved helix within its β-propeller and a short leucine zipper-containing dimeric segment of Cenp-F, mediating localization to nuclear pores in prophase. A point mutation in an adjacent leucine zipper impairs Bub1 interaction and kinetochore targeting of the Cenp-F KT-core domain without affecting Nup133 binding. Cenp-E redundantly contributes with Bub1 to Cenp-F kinetochore recruitment. In silico structural modeling, yeast two-hybrid assays, structure-guided mutagenesis, immunofluorescence localization of mutants EMBO reports High 29632243
2020 CENP-F contains two microtubule-binding domains that make distinct contributions: they stabilize kinetochore-microtubule attachments and contribute to force transduction but are dispensable for chromosome congression. A specialized domain interacts directly with Nde1 to limit dynein-mediated stripping of corona cargoes; this antagonistic activity is crucial for maintaining corona composition and ensuring efficient kinetochore biorientation. CRISPR gene editing, engineered separation-of-function mutants, live-cell imaging, quantitative kinetochore attachment analysis, co-immunoprecipitation The Journal of cell biology High 32207772
2011 Rab5 (a small GTPase that regulates vesicular trafficking) forms a complex with a subset of CENP-F in mitotic cells and regulates the kinetics of CENP-F release from the nuclear envelope and its accumulation on kinetochores. Simultaneous depletion of both Rab5 and CENP-F recapitulates the individual depletion mitotic defects, indicating epistatic roles for these two proteins in chromosome congression. RNAi, co-immunoprecipitation of Rab5 and CENP-F from mitotic cells, immunofluorescence, double-depletion epistasis analysis Proceedings of the National Academy of Sciences of the United States of America Medium 21987812
2010 Both the amino and carboxy termini of KSHV LANA bind to CENP-F, and LANA co-localizes with CENP-F at centromeric regions. LANA also associates with Bub1, which forms a complex with CENP-F. FISH demonstrates co-localization of Bub1, LANA, and KSHV episome tethered to host chromosome. Knockdown of Bub1 (but not CENP-F) dramatically reduces KSHV genome copy number, suggesting the LANA-CENP-F/Bub1 interaction contributes to viral genome persistence. Co-immunoprecipitation, immunofluorescence co-localization, FISH, shRNA knockdown of Bub1 and CENP-F with genome copy number quantification Journal of virology Medium 20660191
2015 CENP-F co-localizes with Ninein at the subdistal appendages of the mother centriole and co-immunoprecipitates with IFT88 from mitotic and serum-starved HEK293 cells. Mutations in CENPF cause ciliopathy with truncated cilia and failure of IFT88 to co-localize with CENP-F along ciliary axonemes, establishing a role for CENP-F in ciliogenesis. Whole exome sequencing, co-immunoprecipitation of CENP-F with IFT88, immunofluorescence co-localization in renal epithelial cells, analysis of patient tissue with CENPF mutations Journal of medical genetics Medium 25564561
2010 RNAi depletion of CENP-F markedly downregulates methylation of histone H3 at K4 and K9, and decreases association of HP1α with mitotic chromosomes, revealing a role for CENP-F in regulating epigenetic histone H3 modifications. RNAi, immunofluorescence for H3K4me and H3K9me, HP1α localization analysis Acta biochimica et biophysica Sinica Low 20213041
2010 Overexpression of C-terminal CENP-F deletion mutants induces interphase chromatin condensation into aggregates. CENP-F associates with DNA-dependent protein kinase (DNA-PK) by co-immunoprecipitation, and the DNA-PK association activity of CENP-F mutants correlates with their ability to induce chromatin aggregation. Overexpression of truncation mutants, co-immunoprecipitation with DNA-PK, in situ hybridization with chromosome painting probes Acta biochimica et biophysica Sinica Low 20978035
2012 Cardiac-specific deletion of CENP-F in murine cardiomyocytes causes decreased cell division, blunted trabeculation, disruption of intercalated discs, loss of microtubule integrity at the costamere, and 100% development of progressive dilated cardiomyopathy with heart block and scarring, establishing a direct genetic link between CENP-F loss and cardiomyopathy. Cre-loxP conditional knockout in murine cardiomyocytes, histology, immunofluorescence for microtubule and intercalated disc components, cardiac functional analysis Disease models & mechanisms High 22563055
2016 CENP-F(-/-) mouse embryonic fibroblasts show severely diminished microtubule dynamics during interphase, which underlies defects in cell migration, focal adhesion dynamics, and primary cilia formation, demonstrating CENP-F regulates MT dynamics and heterogeneous cellular functions outside of cell division. Genetic deletion model (CENP-F(-/-) MEFs), live-cell microtubule dynamics imaging, cell migration assays, immunofluorescence for focal adhesions and cilia Molecular biology of the cell High 27146114
2019 Miro-deficient CENP-F point mutant (deficient in Miro binding) causes a defect in mitochondrial spreading in cultured cells similar to Miro depletion. Mice with this mutation or truncations lacking the farnesylated C-terminus develop normally, indicating the Miro-dependent mitochondrial pool of CENP-F and its farnesylated C-terminus are dispensable for normal murine development. CRISPR/Cas9-engineered CENP-F point mutation abolishing Miro binding, mouse knock-in models, live-cell mitochondrial distribution imaging PLoS genetics High 30856164
2025 Importin beta generates proximity ligation products with CENP-F during mitosis. Importin beta overexpression alters CENP-F mitotic localization (promoting accumulation at spindle poles and decreasing kinetochore association) and causes persistence of CENP-F into late mitosis when it normally disappears, in a process requiring microtubule integrity. This implicates importin beta in the spatial and temporal control of CENP-F during mitosis and reveals a protective role of microtubules against premature CENP-F ubiquitination. Proximity ligation assay, importin beta overexpression, immunofluorescence, microtubule depolymerization experiments Scientific reports Medium 40596417
2025 USP4 interacts with and stabilizes CENP-F via deubiquitination. CENP-F undergoes degradation via the ubiquitination-proteasome pathway in colorectal cancer cells. Clinical samples confirm that USP4 expression positively correlates with CENP-F protein but not mRNA levels, establishing USP4 as a deubiquitinase that controls CENP-F stability. Co-immunoprecipitation, ubiquitination assays, siRNA knockdown, Western blot for protein levels, clinical sample correlation analysis Cell death & disease Medium 39922805
2025 SETDB1-PC4-UPF1 constitutes a post-transcriptional machinery that controls periodic degradation of CENPF mRNA. In early G2, newly synthesized CENPF mRNAs bind to PC4; SETDB1 then dimethylates PC4 at K35. In late G2, dimethylated PC4 interacts with UPF1 to promote deadenylation-dependent degradation of CENPF mRNAs. RNA immunoprecipitation, protein interaction assays, methylation assays, mRNA stability assays, cell cycle synchronization Cell death and differentiation Medium 40016337
2023 CENPF mRNA is subject to N6-methyladenosine (m6A) modification mediated by METTL3. This modification is recognized by HNRNPA2B1, which promotes CENPF mRNA stability. CENPF binds FAK and promotes its cytoplasmic localization; the metastatic function of CENPF is dependent on the MAPK signaling pathway. MeRIP-seq, RNA immunoprecipitation-qPCR, RNA pulldown, co-immunoprecipitation, mass spectrometry, immunofluorescence, gain/loss-of-function experiments Cancer communications Medium 37256823
2024 CENP-F functions with FOXM1 to co-regulate G2/M transcription and proper chromosome segregation. Loss of CENP-F results in altered chromatin accessibility at G2/M genes and reduced FOXM1-MBB complex formation. This FOXM1-CENP-F transcriptional co-regulation is cancer-specific and involves CENP-F acting as an outer kinetochore component that also has a nuclear transcriptional role. CRISPR loss-of-function, ATAC-seq (chromatin accessibility), ChIP, co-immunoprecipitation for FOXM1-MBB complex, chromosome segregation assays Molecular and cellular biology Medium 38779933
2003 DNA damage-induced G2 arrest in HeLa cells (TP53-independent) occurs in early G2, before redistribution of CENP-F to the nuclear envelope and kinetochores and before chromosome condensation commences, using CENP-F localization as a precise cell cycle marker to define the arrest point. DNA damage treatment, immunofluorescence for CENP-F localization as a G2 stage marker, cell cycle analysis Radiation research Medium 12710871
2023 In C. elegans, BUB-1, HCP-1/2 (CENP-F orthologs), and CLS-2 (CLASP) form a BHC kinetochore module that synergistically stabilizes microtubules and promotes microtubule pause. BUB-1 and HCP-1/2 do not only act as targeting factors for CLS-2 but also actively participate in controlling kinetochore-microtubule dynamics to promote meiotic spindle formation and accurate chromosome segregation. In vivo structure-function analysis with RNAi/mutations, in vitro microtubule stabilization and pause assays, live imaging eLife High 36799894
2023 CENPF targets Chk1-mediated G2/M phase arrest and binds to Rb to compete with E2F1 in triple-negative breast cancer cells; this competition at the Rb-E2F1 axis modulates the DNA damage response. Co-immunoprecipitation of CENPF with Rb, ChIP, siRNA knockdown, cell cycle analysis Scientific reports Low 36720923
2025 CENPF interacts with PLA2G4A by co-immunoprecipitation and molecular docking. Silencing CENPF reduces mTORC1 signaling and EMT in glioma cells; the CENPF-PLA2G4A interaction promotes downstream oncogenic signaling. Combined silencing of CENPF and a PLA2G4A inhibitor shows synergistic anti-glioma effects. Molecular docking, co-immunoprecipitation, siRNA knockdown, Western blot for mTORC1 pathway, cell proliferation and invasion assays Cancer cell international Low 40025532

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1995 CENP-F is a protein of the nuclear matrix that assembles onto kinetochores at late G2 and is rapidly degraded after mitosis. The Journal of cell biology 336 7542657
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
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
1993 CENP-F is a .ca 400 kDa kinetochore protein that exhibits a cell-cycle dependent localization. Cell motility and the cytoskeleton 192 7904902
2007 Cenp-F links kinetochores to Ndel1/Nde1/Lis1/dynein microtubule motor complexes. Current biology : CB 139 17600710
2002 Farnesylation of Cenp-F is required for G2/M progression and degradation after mitosis. Journal of cell science 137 12154071
2003 Human CENP-I specifies localization of CENP-F, MAD1 and MAD2 to kinetochores and is essential for mitosis. Nature cell biology 129 12640463
2019 The Human-Specific and Smooth Muscle Cell-Enriched LncRNA SMILR Promotes Proliferation by Regulating Mitotic CENPF mRNA and Drives Cell-Cycle Progression Which Can Be Targeted to Limit Vascular Remodeling. Circulation research 122 31339449
2005 Unstable microtubule capture at kinetochores depleted of the centromere-associated protein CENP-F. The EMBO journal 105 16252009
2016 Dysregulation of miRNAs-COUP-TFII-FOXM1-CENPF axis contributes to the metastasis of prostate cancer. Nature communications 98 27108958
2005 Silencing Cenp-F weakens centromeric cohesion, prevents chromosome alignment and activates the spindle checkpoint. Journal of cell science 95 16219694
2019 HnRNPR-CCNB1/CENPF axis contributes to gastric cancer proliferation and metastasis. Aging 93 31527303
2015 Mitotic redistribution of the mitochondrial network by Miro and Cenp-F. Nature communications 90 26259702
2006 Cenp-F (mitosin) is more than a mitotic marker. Chromosoma 88 16565862
2012 Frequent amplification of CENPF, GMNN and CDK13 genes in hepatocellular carcinomas. PloS one 81 22912832
2006 CENP-F is a novel microtubule-binding protein that is essential for kinetochore attachments and affects the duration of the mitotic checkpoint delay. Chromosoma 80 16601978
2015 The kinetochore protein, CENPF, is mutated in human ciliopathy and microcephaly phenotypes. Journal of medical genetics 75 25564561
2005 The CENP-F-like proteins HCP-1 and HCP-2 target CLASP to kinetochores to mediate chromosome segregation. Current biology : CB 73 15854912
2000 Nonrandom chromosomal imbalances in esophageal squamous cell carcinoma cell lines: possible involvement of the ATF3 and CENPF genes in the 1q32 amplicon. Japanese journal of cancer research : Gann 70 11092977
2018 The kinetochore proteins CENP-E and CENP-F directly and specifically interact with distinct BUB mitotic checkpoint Ser/Thr kinases. The Journal of biological chemistry 69 29748388
1999 HCP-1, a protein involved in chromosome segregation, is localized to the centromere of mitotic chromosomes in Caenorhabditis elegans. The Journal of cell biology 67 10545493
2010 Historical perspectives on the discovery and elucidation of autoantibodies to centromere proteins (CENP) and the emerging importance of antibodies to CENP-F. Autoimmunity reviews 64 20933614
2007 Farnesyl transferase inhibitors impair chromosomal maintenance in cell lines and human tumors by compromising CENP-E and CENP-F function. Molecular cancer therapeutics 62 17431110
1997 High frequency of neoplasia in patients with autoantibodies to centromere protein CENP-F. Clinical and investigative medicine. Medecine clinique et experimentale 61 9336656
2018 Centromere protein F (CENPF), a microtubule binding protein, modulates cancer metabolism by regulating pyruvate kinase M2 phosphorylation signaling. Cell cycle (Georgetown, Tex.) 60 30526248
2020 LncRNA MCM3AP-AS1 promotes breast cancer progression via modulating miR-28-5p/CENPF axis. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 58 32485570
2010 Bub1 and CENP-F can contribute to Kaposi's sarcoma-associated herpesvirus genome persistence by targeting LANA to kinetochores. Journal of virology 58 20660191
2022 CENPF/CDK1 signaling pathway enhances the progression of adrenocortical carcinoma by regulating the G2/M-phase cell cycle. Journal of translational medicine 48 35123514
2011 Small GTPase Rab5 participates in chromosome congression and regulates localization of the centromere-associated protein CENP-F to kinetochores. Proceedings of the National Academy of Sciences of the United States of America 48 21987812
2001 CENP-F gene amplification and overexpression in head and neck squamous cell carcinomas. Head & neck 46 11303627
2007 Heme carrier protein (HCP-1) spatially interacts with the CD163 hemoglobin uptake pathway and is a target of inflammatory macrophage activation. Journal of leukocyte biology 41 17947394
2023 N6-methyladenosine modification of CENPF mRNA facilitates gastric cancer metastasis via regulating FAK nuclear export. Cancer communications (London, England) 38 37256823
2019 Loss of CENPF leads to developmental failure in mouse embryos. Cell cycle (Georgetown, Tex.) 35 31478449
2020 CENP-F stabilizes kinetochore-microtubule attachments and limits dynein stripping of corona cargoes. The Journal of cell biology 32 32207772
2017 CENP-F couples cargo to growing and shortening microtubule ends. Molecular biology of the cell 31 28701340
2009 Murine CENP-F regulates centrosomal microtubule nucleation and interacts with Hook2 at the centrosome. Molecular biology of the cell 30 19793914
2008 Expression of centromere protein F (CENP-F) associated with higher FDG uptake on PET/CT, detected by cDNA microarray, predicts high-risk patients with primary breast cancer. BMC cancer 30 19102762
1994 Chromosomal localization of the genes encoding the kinetochore proteins CENPE and CENPF to human chromosomes 4q24-->q25 and 1q32-->q41, respectively, by fluorescence in situ hybridization. Genomics 30 7851898
2020 TOP2A and CENPF are synergistic master regulators activated in cervical cancer. BMC medical genomics 29 33023625
2019 Downregulation of CENPF Remodels Prostate Cancer Cells and Alters Cellular Metabolism. Proteomics 28 30957416
2011 The kinetochore protein Cenp-F is a potential novel target for zoledronic acid in breast cancer cells. Journal of cellular and molecular medicine 28 20015195
1999 Immunohistochemical analysis of the proliferation associated nuclear antigen CENP-F in non-Hodgkin's lymphoma. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 28 9950165
2020 Anti-platelet adhesion and in situ capture of circulating endothelial progenitor cells on ePTFE surface modified with poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) and hemocompatible peptide 1 (HCP-1). Colloids and surfaces. B, Biointerfaces 26 32447201
2021 CENPF promotes papillary thyroid cancer progression by mediating cell proliferation and apoptosis. Experimental and therapeutic medicine 25 33680123
2013 The microtubule binding properties of CENP-E's C-terminus and CENP-F. Journal of molecular biology 25 23892111
2016 Strømme Syndrome Is a Ciliary Disorder Caused by Mutations in CENPF. Human mutation 24 26820108
2016 Progerin impairs chromosome maintenance by depleting CENP-F from metaphase kinetochores in Hutchinson-Gilford progeria fibroblasts. Oncotarget 24 27015553
2009 Silencing CENPF in bovine preimplantation embryo induces arrest at 8-cell stage. Reproduction (Cambridge, England) 23 19651849
2008 Murine CENPF interacts with syntaxin 4 in the regulation of vesicular transport. Journal of cell science 23 18827011
2008 Genetic analysis of the spindle checkpoint genes san-1, mdf-2, bub-3 and the CENP-F homologues hcp-1 and hcp-2 in Caenorhabditis elegans. Cell division 22 18248670
2021 Knockdown of CENPF inhibits the progression of lung adenocarcinoma mediated by ERβ2/5 pathway. Aging 20 33428600
2012 Cardiac-specific deletion of the microtubule-binding protein CENP-F causes dilated cardiomyopathy. Disease models & mechanisms 20 22563055
2018 Disentangling the molecular determinants for Cenp-F localization to nuclear pores and kinetochores. EMBO reports 19 29632243
2023 CENPF knockdown inhibits adriamycin chemoresistance in triple-negative breast cancer via the Rb-E2F1 axis. Scientific reports 17 36720923
2022 Investigation of Functional Synergism of CENPF and FOXM1 Identifies POLD1 as Downstream Target in Hepatocellular Carcinoma. Frontiers in medicine 17 35865168
2018 The different roles of hcp1 and hcp2 of the type VI secretion system in Escherichia coli strain CE129. Journal of basic microbiology 17 30247772
2017 Mechanism for G2 phase-specific nuclear export of the kinetochore protein CENP-F. Cell cycle (Georgetown, Tex.) 17 28723232
2018 Loss of CENP-F Results in Dilated Cardiomyopathy with Severe Disruption of Cardiac Myocyte Architecture. Scientific reports 16 29765066
2021 Endothelial cell adhesion and blood response to hemocompatible peptide 1 (HCP-1), REDV, and RGD peptide sequences with free N-terminal amino groups immobilized on a biomedical expanded polytetrafluorethylene surface. Biomaterials science 15 33336665
2019 Miro-dependent mitochondrial pool of CENP-F and its farnesylated C-terminal domain are dispensable for normal development in mice. PLoS genetics 15 30856164
2016 Loss of CENP-F results in distinct microtubule-related defects without chromosomal abnormalities. Molecular biology of the cell 15 27146114
2021 Upregulation of CENPF is linked to aggressive features of osteosarcoma. Oncology letters 14 34386070
2003 DNA damage in HeLa cells induced arrest at a discrete point in G2 phase as defined by CENP-F localization. Radiation research 14 12710871
2021 Identification of potential key genes and functional role of CENPF in osteosarcoma using bioinformatics and experimental analysis. Experimental and therapeutic medicine 13 34934449
2019 Malformations in the Murine Kidney Caused by Loss of CENP-F Function. Anatomical record (Hoboken, N.J. : 2007) 13 30408335
2020 Expanding the phenotype and the genotype of Stromme syndrome: A novel variant of the CENPF gene and literature review. European journal of medical genetics 12 31953238
2017 A further family of Stromme syndrome carrying CENPF mutation. American journal of medical genetics. Part A 12 28407396
2024 Contribution of CENP-F to FOXM1-Mediated Discordant Centromere and Kinetochore Transcriptional Regulation. Molecular and cellular biology 11 38779933
2018 Regulation of Cenp-F localization to nuclear pores and kinetochores. Cell cycle (Georgetown, Tex.) 11 30198378
2024 Knockdown of NFIC Promotes Bovine Myoblast Proliferation through the CENPF/CDK1 Axis. Journal of agricultural and food chemistry 10 38780097
2023 Synergistic stabilization of microtubules by BUB-1, HCP-1, and CLS-2 controls microtubule pausing and meiotic spindle assembly. eLife 10 36799894
2022 MiR-1-3p targets CENPF to repress tumor-relevant functions of gastric cancer cells. BMC gastroenterology 10 35346060
2023 CENPF promotes the proliferation of renal cell carcinoma in vitro. Translational andrology and urology 8 36915885
2010 Involvement of CENP-F in histone methylation. Acta biochimica et biophysica Sinica 8 20213041
2022 CircDLG1 promotes malignant development of non-small cell lung cancer through regulation of the miR-630/CENPF axis. Strahlentherapie und Onkologie : Organ der Deutschen Rontgengesellschaft ... [et al] 7 35748916
2021 miR-383-5p inhibits human malignant melanoma cells function via targeting CENPF. Reproductive biology 7 34274651
2025 CENPF interaction with PLA2G4A promotes glioma growth by modulating mTORC1 and NF-κB pathways. Cancer cell international 6 40025532
2022 Biallelic variants in CENPF causing a phenotype distinct from Strømme syndrome. American journal of medical genetics. Part C, Seminars in medical genetics 6 35488810
2025 USP4-mediated CENPF deubiquitylation regulated tumor metastasis in colorectal cancer. Cell death & disease 5 39922805
2025 CENPF (+) cancer cells promote malignant progression of early-stage TP53 mutant lung adenocarcinoma. Oncogenesis 5 40044674
2022 Combined multiomics analysis reveals the mechanism of CENPF overexpression-mediated immune dysfunction in diffuse large B-cell lymphoma in vitro. Frontiers in genetics 5 36644760
2020 XBP1 negatively regulates CENPF expression via recruiting ATF6α to the promoter during ER stress. Cancer cell international 5 32973403
2025 PSMD14/E2F1 Axis-Mediated CENPF Promotes the Metastasis of Triple-Negative Breast Cancer Through Inhibiting Ferroptosis. Cancer science 4 40365861
2023 The Role of BDNF, YBX1, CENPF, ZSCAN4, TEAD4, GLIS1 and USF1 in the Activation of the Embryonic Genome in Bovine Embryos. International journal of molecular sciences 4 38003209
2017 Calcium depletion destabilises kinetochore fibres by the removal of CENP-F from the kinetochore. Scientific reports 4 28779172
2025 The SETDB1-PC4-UPF1 post-transcriptional machinery controls periodic degradation of CENPF mRNA and maintains mitotic progression. Cell death and differentiation 3 40016337
2025 Reduction of NFX1-123 and HPV 16 E6 and E7 Decreased Telomerase and CENP-F in Cervical Cancer Cell Lines. Cancers 3 40563693
2024 Knockdown of CENPF induces cell cycle arrest and inhibits epithelial‑mesenchymal transition progression in glioma. Oncology letters 3 39611064
2022 Centromere Protein F (CENPF): A novel marker for salivary gland pathology. Journal of oral and maxillofacial pathology : JOMFP 3 36588828
2010 Involvement of Cenp-F in interphase chromatin organization possibly through association with DNA-dependent protein kinase. Acta biochimica et biophysica Sinica 3 20978035
2025 CENPF as a Potential Biomarker Associated with the Immune Microenvironment of Renal Cancer. Technology in cancer research & treatment 2 40165474
2025 The localisation and stability of the CENP-F protein are regulated by importin beta and microtubules in mitotic cells. Scientific reports 2 40596417
2024 CENPF Upregulation is Associated with Immunosuppressive Status and Poor Clinical Outcomes in Lung Adenocarcinoma Validated by qRT-PCR. Combinatorial chemistry & high throughput screening 2 37287300
2024 Role of CENPF and NDC80 in the rehabilitation nursing of hepatocellular carcinoma and cirrhosis: An observational study. Medicine 2 38701255
2023 Novel Loss of Function Variants in CENPF Including a Large Intragenic Deletion in Patients with Strømme Syndrome. Genes 2 38002928
2025 CENPF overexpression in bladder cancer cells enhances proliferation, migration, invasion, and apoptosis. Scientific reports 1 40659783
2025 CENP-F promotes HCC cell proliferation mediated by super enhancer reader BRD4. Discover oncology 1 41160272
2023 Contribution of CENP-F to FOXM1-mediated discordant centromere and kinetochore transcriptional regulation. bioRxiv : the preprint server for biology 1 38234763
2019 CUGC for Stromme syndrome and CENPF-related disorders. European journal of human genetics : EJHG 1 31488893

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