Affinage

CENPW

Centromere protein W · UniProt Q5EE01

Length
88 aa
Mass
10.1 kDa
Annotated
2026-06-09
26 papers in source corpus 15 papers cited in narrative 15 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CENPW (also known as CUG2 or C6orf173) encodes an inner kinetochore protein that ensures the fidelity of chromosome segregation in both mitosis and meiosis (PMID:19533040, PMID:32446395). It forms a centromeric complex with CENP-T and CENP-A, co-localizes with centromeric markers, and is required for accurate chromosome segregation; its depletion causes aberrant cell division, multipolar spindle fragmentation, loss of Hec1 from kinetochores, and acentriolar spindle poles in a manner dependent on microtubules and Eg5 motor activity, indicating it sustains kinetochore-microtubule attachments against motor-generated traction forces (PMID:19533040, PMID:25329824). In mouse oocytes CENP-W concentrates on kinetochores during meiotic maturation, and its loss produces kinetochore-microtubule detachment, chromosome misalignment, metaphase I arrest, and spindle assembly checkpoint activation (PMID:32446395). CENP-W abundance is set by proteasomal control: CSN5/JAB1 directly drives ubiquitin-dependent degradation of both CENP-T and CENP-W, while heterodimer formation with CENP-T mutually stabilizes the pair and is required for their kinetochore recruitment (PMID:23926101). Stability and proper prophase localization are further controlled by nucleophosmin/B23 (NPM1), with which CENP-W physically associates in the nucleolus and nuclear matrix (PMID:22002061), and by hnRNP U, which co-stabilizes CENP-W and co-localizes with it at the microtubule-kinetochore interface (PMID:26881882). Beyond the kinetochore, CENP-W incorporates into the SCFβ-TrCP1 ubiquitin ligase through SKP1-overlapping sites, promoting complex disassembly and β-TrCP1 degradation, thereby preserving CDC25A levels to permit timely G2/M entry (PMID:29863914), and it associates with EZH2 to enhance its stability and facilitate PRC2-mediated H3K27me3 gene silencing at target promoters (PMID:26111449).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 2007 Medium

    Established CENPW as a nuclear protein with oncogenic potential, raising the question of its normal molecular role.

    Evidence EGFP-fusion localization plus soft-agar and nude-mouse xenograft transformation assays in NIH3T3 cells

    PMID:17610844

    Open questions at the time
    • No mechanism linking nuclear localization to transformation
    • Overexpression phenotype only, no loss-of-function
  2. 2009 High

    Defined CENPW as a centromere component by showing it binds CENP-T and CENP-A and is required for chromosome segregation, anchoring its function at the kinetochore.

    Evidence Yeast two-hybrid, Co-IP, immunofluorescence, and siRNA knockdown with division phenotype

    PMID:19533040

    Open questions at the time
    • Stoichiometry and architecture of the CENP-T/CENP-W complex not resolved
    • Mechanism of microtubule attachment not addressed
  3. 2010 Medium

    Identified Sp1/Sp3 control of the CENPW promoter, explaining how its expression is coupled to proliferative cues.

    Evidence Promoter deletion, EMSA with mutagenesis, and supershift assays under serum stimulation

    PMID:20180024

    Open questions at the time
    • Does not connect transcriptional control to cell-cycle timing of CENP-W function
  4. 2010 Medium

    Placed CUG2-driven oncogenic signaling through Ras and p38 MAPK by epistasis with selective kinase inhibitors.

    Evidence Pharmacological inhibitor epistasis in stable CUG2-overexpressing cells with viral replication readout

    PMID:20075984

    Open questions at the time
    • Direct biochemical link between CENP-W and these kinases not established
    • Overexpression context only
  5. 2011 High

    Showed nucleophosmin/B23 controls CENP-W stability and prophase localization, identifying a nucleolar regulator of the protein.

    Evidence Subnuclear fractionation, RNA/DNA association, Co-IP, and B23 siRNA with localization readout

    PMID:22002061

    Open questions at the time
    • Functional consequence of RNA/nuclear-matrix association unresolved
    • Mechanism of B23-dependent stabilization unknown
  6. 2011 Medium

    Demonstrated an in vivo mitotic requirement for cug2 in vertebrate neurogenesis, validating the segregation role in a whole organism.

    Evidence Morpholino knockdown in zebrafish with spindle/chromosome immunofluorescence and apoptosis assays

    PMID:21838932

    Open questions at the time
    • Morpholino off-target effects not excluded
    • Molecular partners in vivo not examined
  7. 2013 High

    Resolved how CENP-W levels are set, showing CSN5/JAB1 degrades it while CENP-T heterodimerization protects it, coupling complex assembly to kinetochore recruitment.

    Evidence Yeast two-hybrid, Co-IP, ubiquitination/proteasome degradation assays, and kinetochore recruitment imaging

    PMID:23926101

    Open questions at the time
    • Ubiquitin ligase acting downstream of CSN5 not identified
    • Quantitative balance of degradation vs. stabilization not measured
  8. 2014 High

    Defined the mechanical role of CENP-W in maintaining kinetochore-microtubule attachments that resist motor-generated forces.

    Evidence RNAi, live imaging, nocodazole/monastrol epistasis, and TPX2 overexpression rescue in HeLa cells

    PMID:25329824

    Open questions at the time
    • Direct role in load-bearing not biochemically measured
    • Link to centriole splitting mechanism unclear
  9. 2015 Medium

    Connected CENP-W to transcriptional repression by showing it stabilizes EZH2 and localizes to PRC2 target promoters.

    Evidence Co-IP, protein stability assays, and ChIP

    PMID:26111449

    Open questions at the time
    • Whether EZH2 stabilization is direct not resolved
    • Genome-wide repression scope not defined
  10. 2016 Medium

    Identified hnRNP U as a mutual-stabilization partner linking CENP-W to microtubule organization.

    Evidence Co-IP, proteasome inhibitor assays, co-localization, siRNA, and microtubule drug manipulation

    PMID:26881882

    Open questions at the time
    • Reciprocal validation of interaction limited
    • Mechanism coupling protein stability to microtubule state unknown
  11. 2018 High

    Uncovered a cell-cycle role distinct from the kinetochore: CENP-W disassembles SCFβ-TrCP1 to preserve CDC25A and enable G2/M entry.

    Evidence Co-IP, complex disassembly assays, and siRNA with CDC25A and mitotic-timing readout

    PMID:29863914

    Open questions at the time
    • How nuclear pool is partitioned between kinetochore and SCF roles unclear
    • Direct contribution to other β-TrCP1 substrates not assessed
  12. 2018 Medium

    Refined β-TrCP1 engagement, showing isoform-selective binding and CENP-W-dependent nuclear-cytoplasmic shuttling of β-TrCP1.

    Evidence Co-transfection binding assays and fluorescence imaging with NLS-defective CENP-W mutant

    PMID:30267325

    Open questions at the time
    • Functional significance of isoform preference not tested
    • Limited mechanistic depth
  13. 2019 Medium

    Linked CUG2-induced stemness to an NPM1→TGF-β axis, extending its oncogenic activity to a defined signaling route.

    Evidence NPM1 siRNA, sphere formation, TGF-β reporter, and Smad2 siRNA epistasis

    PMID:31113615

    Open questions at the time
    • Direct molecular trigger of TGF-β activity not defined
    • Overexpression-driven phenotype
  14. 2020 Medium

    Established a meiotic requirement, showing CENP-W is needed for kinetochore-microtubule attachment and metaphase I progression in oocytes.

    Evidence Confocal localization and siRNA microinjection in mouse oocytes with attachment and SAC readouts

    PMID:32446395

    Open questions at the time
    • Meiosis-specific partners not identified
    • Single-lab loss-of-function
  15. 2023 Low

    Predicted residues governing CENP-T/CENP-W dimerization, offering a structural hypothesis for complex assembly.

    Evidence Molecular docking, binding free energy, and MD simulations with in silico mutagenesis

    PMID:37943107

    Open questions at the time
    • Computational only, awaits experimental validation of LEU83/ARG53
    • No structure of the human complex determined

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the kinetochore, SCFβ-TrCP1/cell-cycle, and PRC2/transcriptional activities of CENP-W are spatially and temporally coordinated within a single cell remains unresolved.
  • No experimental partitioning of CENP-W pools across its distinct functions
  • No high-resolution structure of any CENP-W complex

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 2 GO:0098772 molecular function regulator activity 2 GO:0003723 RNA binding 1
Localization
GO:0005634 nucleus 2 GO:0005694 chromosome 2 GO:0005730 nucleolus 1
Pathway
R-HSA-1640170 Cell Cycle 3 R-HSA-4839726 Chromatin organization 1
Partners
BTRCCENPACENPTCSN5/JAB1CUL1EZH2HNRNPUNPM1
Complex memberships
CENP-T/CENP-W heterodimerSCFβ-TrCP1 ubiquitin ligasekinetochore

Evidence

Reading pass · 15 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2007 CENPW (CUG2) protein localizes predominantly to the nucleus when expressed as EGFP fusion, and overexpression in NIH3T3 mouse fibroblasts induces cancer-specific phenotypes in vitro and tumor formation in nude mice, establishing proto-oncogenic activity. EGFP fusion protein localization imaging; soft-agar and nude mouse xenograft assays Biochemical and biophysical research communications Medium 17610844
2009 CENPW (CUG2) physically interacts with CENP-T (a component of the CENP-A nucleosome complex) and CENP-A in a centromeric complex, co-localizes with centromeric markers, and is required for proper chromosome segregation during mitosis; its depletion induces aberrant cell division. Yeast two-hybrid screening; co-immunoprecipitation; immunofluorescent staining; siRNA knockdown with cell viability and division phenotype readout Molecules and cells High 19533040
2010 The CENPW promoter contains a GC-rich Sp1-binding site (-46 to -36) that is critical for basal and serum-induced expression; Sp1 and Sp3 transcription factors specifically bind this site and mediate transactivation of CENPW. Promoter deletion analysis; competitive EMSA with mutated oligos; supershift assays with Sp1/Sp3 antibodies; serum stimulation experiments Molecular biology reports Medium 20180024
2010 CUG2 expression activates MAPK (ERK, JNK, p38), Src kinase, and Ras signaling; inhibition of Ras or p38 MAPK (but not ERK, JNK, or Src) blocks reoviral replication in CUG2-expressing cells, establishing Ras and p38 as necessary downstream effectors of CUG2-mediated permissiveness to reovirus. Pharmacological inhibitors of specific kinases; stable CUG2-overexpressing NIH3T3 cells; viral replication assays Cancer gene therapy Medium 20075984
2011 CENPW (CENP-W) localizes to the nucleolus and nuclear matrix, associates with both RNA and DNA by fractionation, and physically interacts with the nucleolar phosphoprotein nucleophosmin (B23/NPM1); depletion of B23 by siRNA decreases CENP-W protein stability and causes its severe mislocalization during prophase. Subnuclear fractionation; RNA/DNA association assays; biochemical affinity binding (co-IP); siRNA knockdown; immunofluorescence microscopy The Journal of biological chemistry High 22002061
2011 In zebrafish, morpholino-mediated knockdown of cug2 causes mitotic arrest with abnormal spindle formation and chromosome misalignment in the neural plate, followed by CNS-wide apoptosis, establishing an in vivo requirement for Cug2 in normal mitosis during neurogenesis. Morpholino knockdown in zebrafish embryos; spindle/chromosome immunofluorescence; apoptosis assays BMC developmental biology Medium 21838932
2013 CSN5/JAB1 directly interacts with both CENP-T and CENP-W (identified by yeast two-hybrid and confirmed by Co-IP), promotes their ubiquitin- and proteasome-dependent degradation, and formation of the CENP-T·CENP-W complex stabilizes both proteins by blocking CSN5-mediated degradation; dysregulation of CSN5 causes severe defects in CENP-T·CENP-W recruitment to the kinetochore during prophase. Yeast two-hybrid; co-immunoprecipitation; ubiquitination/proteasome degradation assays; immunofluorescence of kinetochore recruitment The Journal of biological chemistry High 23926101
2014 CENP-W depletion in HeLa cells causes bipolar spindle fragmentation into multipolar spindles, depletion of Hec1 at kinetochores, abnormal centriole splitting, and generation of acentriolar spindle poles; spindle pole fragmentation requires microtubules (absent in nocodazole) and Eg5 motor activity (reduced by monastrol), implicating CENP-W in maintaining kinetochore-microtubule attachment that resists motor-generated traction forces. RNAi depletion; live-cell fluorescence imaging (H2B and tubulin); immunofluorescence of centrioles and centrosomal markers; pharmacological manipulation (nocodazole, monastrol); TPX2 overexpression rescue PloS one High 25329824
2015 CENP-W physically associates with EZH2 (catalytic subunit of PRC2), enhances EZH2 protein stability, and is recruited to the promoters of EZH2 target genes (by chromatin immunoprecipitation) to facilitate EZH2-mediated transcriptional repression (H3K27me3-associated gene silencing). Co-immunoprecipitation; protein stability assays; chromatin immunoprecipitation (ChIP) Biochemical and biophysical research communications Medium 26111449
2016 CENP-W physically interacts with hnRNP U; the interaction mutually stabilizes both proteins by inhibiting proteasome-mediated degradation. They co-localize in the nuclear matrix during interphase and at the microtubule-kinetochore interface during mitosis. CENP-W depletion causes loss of microtubules and defects in microtubule organization, and both microtubule-stabilizing and -destabilizing agents decrease CENP-W protein stability. Co-immunoprecipitation; proteasome inhibitor assays; co-localization immunofluorescence; siRNA knockdown; pharmacological microtubule manipulation PloS one Medium 26881882
2018 CENP-W interacts with CUL1 and β-TrCP1 (F-box protein of SCFβ-TrCP1 ubiquitin ligase) through sites overlapping with SKP1 binding; CENP-W incorporation into the SCFβ-TrCP1 complex promotes complex disassembly and β-TrCP1 degradation, thereby decreasing SCFβ-TrCP1 activity. At the G2/M transition, CENP-W knockdown decreases CDC25A protein levels, delaying mitotic entry. Co-immunoprecipitation; complex disassembly assays; siRNA knockdown with CDC25A protein level and mitotic timing readout; cell cycle synchronization FASEB journal High 29863914
2018 CENP-W binds both b and f isoforms of β-TrCP1 but with greater affinity for the b isoform; CENP-W (NLS-defective mutant) regulates nuclear-cytoplasmic shuttling of both β-TrCP1 isoforms with preference for isoform b; the Elongin C-binding motif in isoform b contributes to this specificity. In vivo binding assay (co-transfection/co-IP); fluorescence microscopy of EGFP-β-TrCP1 isoforms with NLS-defective CENP-W mutant Genes & genomics Medium 30267325
2019 CENP-W/CUG2-induced stemness-like phenotypes (sphere formation, stemness factor expression) require NPM1 (nucleophosmin): NPM1 suppression by siRNA blocks CUG2-mediated stemness and diminishes TGF-β transcriptional activity and signaling, placing NPM1 upstream of TGF-β in the CUG2 stemness pathway. siRNA knockdown of NPM1; sphere formation assay; TGF-β reporter assay; Western blotting; epistasis via TGF-β inhibitor and Smad2 siRNA Biochemical and biophysical research communications Medium 31113615
2020 In mouse oocytes, CENP-W localizes to the germinal vesicle at GV stage and becomes concentrated on kinetochores during meiotic maturation; siRNA knockdown of CENP-W causes kinetochore-microtubule detachment, defective spindles, chromosome misalignment, metaphase I arrest, failure of first polar body extrusion, and spindle assembly checkpoint activation. Confocal microscopy (localization); siRNA microinjection in mouse oocytes; immunofluorescence of kinetochore-microtubule attachment; spindle assembly checkpoint assay Biochemical and biophysical research communications Medium 32446395
2023 Computational modeling (molecular docking, binding free energy calculations, and 250 ns MD simulations with site-directed mutagenesis in silico) identified LEU83 and ARG53 in CENP-W as critical residues for CENP-T/CENP-W heterodimer formation; substitution of these residues with lysine significantly disrupts dimerization. Molecular docking; binding free energy calculations; molecular dynamics simulation; in silico site-directed mutagenesis Journal of cellular biochemistry Low 37943107

Source papers

Stage 0 corpus · 26 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2007 Molecular cloning and functional analysis of a novel oncogene, cancer-upregulated gene 2 (CUG2). Biochemical and biophysical research communications 41 17610844
2018 STAT1‑HDAC4 signaling induces epithelial‑mesenchymal transition and sphere formation of cancer cells overexpressing the oncogene, CUG2. Oncology reports 36 30226605
2009 Cancer-upregulated gene 2 (CUG2), a new component of centromere complex, is required for kinetochore function. Molecules and cells 32 19533040
2017 Increased EGFR expression induced by a novel oncogene, CUG2, confers resistance to doxorubicin through Stat1-HDAC4 signaling. Cellular oncology (Dordrecht, Netherlands) 28 28776259
2011 New centromeric component CENP-W is an RNA-associated nuclear matrix protein that interacts with nucleophosmin/B23 protein. The Journal of biological chemistry 25 22002061
2010 CUG2, a novel oncogene confers reoviral replication through Ras and p38 signaling pathway. Cancer gene therapy 25 20075984
2019 Cancer upregulated gene (CUG)2 elevates YAP1 expression, leading to enhancement of epithelial-mesenchymal transition in human lung cancer cells. Biochemical and biophysical research communications 22 30771899
2020 Histone-fold centromere protein W (CENP-W) is associated with the biological behavior of hepatocellular carcinoma cells. Bioengineered 21 32635817
2021 Knockdown of CENPW Inhibits Hepatocellular Carcinoma Progression by Inactivating E2F Signaling. Technology in cancer research & treatment 17 33973496
2019 Cancer upregulated gene 2 (CUG2), a novel oncogene, promotes stemness-like properties via the NPM1-TGF-β signaling axis. Biochemical and biophysical research communications 16 31113615
2016 Centromere Protein (CENP)-W Interacts with Heterogeneous Nuclear Ribonucleoprotein (hnRNP) U and May Contribute to Kinetochore-Microtubule Attachment in Mitotic Cells. PloS one 16 26881882
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
2018 CENP-W inhibits CDC25A degradation by destabilizing the SCFβ-TrCP-1 complex at G2/M. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 11 29863914
2014 Suppression of autophagic genes sensitizes CUG2-overexpressing A549 human lung cancer cells to oncolytic vesicular stomatitis virus-induced apoptosis. International journal of oncology 10 24452380
2018 N-Benzyl-N-methyl-dodecan-1-amine, a novel compound from garlic, exerts anti-cancer effects on human A549 lung cancer cells overexpressing cancer upregulated gene (CUG)2. European journal of pharmacology 9 30287155
2014 CENP-W plays a role in maintaining bipolar spindle structure. PloS one 9 25329824
2010 Sp1 and Sp3 mediate basal and serum-induced expression of human CENP-W. Molecular biology reports 9 20180024
2020 Overexpression of Cancer Upregulated Gene 2 (CUG2) Decreases Spry2 Through c-Cbl, Leading to Activation of EGFR and β-Catenin Signaling. Cancer management and research 8 33116878
2015 A new kinetochore component CENP-W interacts with the polycomb-group protein EZH2 to promote gene silencing. Biochemical and biophysical research communications 8 26111449
2024 CENPW knockdown inhibits progression of bladder cancer through inducing cell cycle arrest and apoptosis. Journal of Cancer 6 38213721
2010 Cancer-upregulated gene 2 (CUG2) overexpression induces apoptosis in SKOV-3 cells. Cell biochemistry and function 6 20648695
2020 CENP-W regulates kinetochore-microtubule attachment and meiotic progression of mouse oocytes. Biochemical and biophysical research communications 5 32446395
2011 Cug2 is essential for normal mitotic control and CNS development in zebrafish. BMC developmental biology 5 21838932
2023 Rare ROS1-CENPW gene in pancreatic acinar cell carcinoma and the effect of crizotinib plus AG chemotherapy: A case report. World journal of clinical cases 4 37727713
2018 Two major alternative splice variants of beta-TrCP1 interact with CENP-W with different binding preferences. Genes & genomics 2 30267325
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

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