Affinage

Showing CUX1 — CDP is a alias.

CUX1

Homeobox protein cut-like 1 · UniProt P39880

Length
1505 aa
Mass
164.2 kDa
Annotated
2026-06-09
100 papers in source corpus 34 papers cited in narrative 34 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CUX1 (CDP/Cut) is a homeodomain transcription factor that uses CUT-repeat and homeodomain DNA-binding modules to control gene programs governing cell-cycle progression, the DNA damage response, and tissue development, and that functions as a haploinsufficient tumor suppressor (PMID:12665598, PMID:24618719, PMID:24316979). Multiple functional isoforms are produced from the full-length p200 protein: nuclear cathepsin L proteolytically processes CUX1 during the G1/S transition to generate the stably DNA-binding p110 (and p90) isoform (PMID:15099520, PMID:16972798), while a shorter p75 isoform arises from transcription initiation within intron 20 (PMID:12438259). The DNA-binding activity of p110 is cell-cycle gated — activated at G1/S by Cdc25A dephosphorylation and processing (PMID:11403998), then inhibited in G2 by cyclin A-Cdk1 phosphorylation at S1237/S1270 (PMID:11584018). Functionally, CUX1 acts as both an activator and a repressor: it activates the DNA polymerase alpha promoter in S phase (PMID:12665598), cooperates with E2F1 to drive G2/M expression of the cytokinesis genes Ect2, MgcRacGAP, and MKLP1 (PMID:19015243), and represses cell-cycle inhibitors including p21 (PMID:11584018) and p27(Kip1), the latter via recruitment of the co-repressor Grg4 with HDAC1/HDAC3 (PMID:19332113, PMID:20485671). Independent of transcription, the CUT domains act as ancillary base-excision-repair factors that directly stimulate OGG1 and APE1 enzymatic activity and are rapidly recruited to damage sites to accelerate repair (PMID:24618719, PMID:29036362, PMID:28147323), while CUX1 also transcriptionally sustains ATM/ATR expression and recruits the histone methyltransferase EHMT2 to double-strand breaks to drive H3K9/H3K27 methylation and 53BP1 recruitment (PMID:22319212, PMID:34473231). As a tumor suppressor, CUX1 directly represses the PI3K inhibitor PIK3IP1 and the apoptosis regulator CFLAR, such that CUX1 haploinsufficiency de-represses these targets, activating PI3K-AKT signaling and promoting apoptosis evasion in myeloid neoplasms (PMID:24316979, PMID:29592892, PMID:33931647). CUX1 additionally partners with NF-κB p65 to modulate chemokine transcription in inflammation (PMID:24336331, PMID:32079724) and, with Cux2, regulates dendritic and synaptic development in cortical neurons (PMID:20510857).

Mechanistic history

Synthesis pass · year-by-year structured walk · 20 steps
  1. 1992 Medium

    Established the founding biochemical identity of mammalian CUX1 as a sequence-specific nuclear DNA-binding protein related to Drosophila Cut that represses tissue-specific transcription.

    Evidence cDNA cloning, EMSA, and cotransfection repression assays

    PMID:1363085

    Open questions at the time
    • No isoform structure or cell-cycle regulation defined
    • Direct target genes not yet mapped
  2. 1997 Medium

    Defined how CUX1 contacts DNA and represses targets, showing CUT repeat CR3 plus the homeodomain are both required for binding, and linked CUX1 to repression of myeloid maturation genes.

    Evidence GST pulldown domain mapping, EMSA supershift, and reporter assays on c-mos and lactoferrin promoters

    PMID:9130595 PMID:9326246

    Open questions at the time
    • Did not address isoform-specific binding
    • No genome-wide target identification
  3. 2001 High

    Resolved how CUX1 DNA binding is gated across the cell cycle, showing G1/S activation by Cdc25A dephosphorylation and processing, and G2 inhibition by cyclin A-Cdk1 phosphorylation at S1237/S1270 that relieves p21 repression.

    Evidence Cell synchronization, EMSA, in vitro kinase/binding assays, S1237A/S1270A mutagenesis, and reporter assays

    PMID:11403998 PMID:11584018

    Open questions at the time
    • Identity of the processing protease not established here
    • Did not address activator function
  4. 2002 Medium

    Demonstrated isoform diversification by identifying the p75 isoform from intronic transcription initiation and confirming CUX1 DNA binding and nuclear localization require the C-terminal homeodomain in vivo.

    Evidence Isoform characterization, reporter assays, transgenic/targeted mouse models, and EMSA

    PMID:11839809 PMID:12438259

    Open questions at the time
    • Mechanism generating p110 still unresolved
    • Physiological relevance of histone gene targets unclear
  5. 2003 High

    Revealed that processed N-terminally truncated CUX1 acts as a transcriptional activator, not just repressor, occupying the DNA polymerase alpha promoter specifically in S phase.

    Evidence ChIP, reporter assays, retroviral expression, and linker scanning

    PMID:12665598

    Open questions at the time
    • Determinants of activator vs repressor switching not defined
    • Cofactors for activation unknown
  6. 2004 High

    Identified nuclear cathepsin L as the protease that generates the p110 isoform during G1/S, providing the mechanistic basis for cell-cycle-coupled CUX1 activation.

    Evidence Cathepsin L knockout cells, ectopic expression, activity-based probes, and in situ processing assays

    PMID:15099520

    Open questions at the time
    • Cleavage site not precisely mapped here
    • Regulation of nuclear cathepsin L entry incompletely defined
  7. 2004 Low

    Connected CUX1 to developmental signaling and chromatin-anchoring repression, linking it to Notch via TLE-4 and to matrix-attachment-region repression via SMAR1.

    Evidence Co-IP, immunofluorescence colocalization, and reporter assays in kidney and lymphoid models

    PMID:15371550 PMID:15499562

    Open questions at the time
    • TLE-4 link rests on a single Co-IP and overexpression
    • Functional consequences of SMAR1 interaction in vivo unclear
  8. 2006 Medium

    Mapped the cathepsin L-generated p90 isoform N-terminus and showed it shares DNA-binding and transcriptional activity with p110, refining the processing model.

    Evidence Deletion-mutant mapping and co-expression with active cathepsin L isoforms

    PMID:16972798

    Open questions at the time
    • Distinct in vivo roles of p90 vs p110 not separated
  9. 2008 High

    Extended CUX1 activator function into mitosis, showing cooperation with E2F1 to drive G2/M expression of cytokinesis genes Ect2, MgcRacGAP, and MKLP1.

    Evidence ChIP, promoter-luciferase assays, siRNA knockdown, and dominant-negative expression

    PMID:19015243

    Open questions at the time
    • Direct physical CUX1-E2F1 complex not structurally defined
  10. 2009 High

    Established a co-repressor mechanism for p27(Kip1) repression in vivo, showing Cux1 recruits Grg4 with HDAC1/HDAC3 to the promoter in kidney tissue.

    Evidence In vivo ChIP, Co-IP, reporter assays, and DNase I footprinting

    PMID:19332113

    Open questions at the time
    • Generality across tissues not addressed
  11. 2010 High

    Defined developmental and pro-invasive roles, showing Cux1/Cux2 control dendrite and synapse formation via Xlr3b/Xlr4b, that CUX1 represses p27 to regulate dendrite complexity through RhoA, and that CUX1 promotes EMT/invasion via Snail/Slug.

    Evidence Knockout mice, electrophysiology, behavior, neuronal gain/loss-of-function, ChIP-chip, and invasion assays

    PMID:20224295 PMID:20485671 PMID:20510857

    Open questions at the time
    • Isoform contributions to neuronal phenotypes not separated
    • Pro-invasive role context dependence unclear
  12. 2012 High

    Showed CUX1 broadly sustains the DNA damage response by transcriptionally maintaining ATM/ATR expression, with knockdown impairing checkpoint signaling and repair.

    Evidence Genome-wide ChIP-chip, RNAi, genetic inactivation, damage foci imaging, and clonogenic survival

    PMID:22319212

    Open questions at the time
    • Did not yet distinguish transcriptional from direct repair roles
  13. 2013 High

    Defined CUX1 as a haploinsufficient tumor suppressor acting through PI3K, showing direct repression of PIK3IP1 such that CUX1 loss activates PI3K-AKT and enhances tumor growth, and revealing NF-κB-coupled inflammatory repression.

    Evidence ChIP, reporter assays, Drosophila and mouse transposon models, pharmacological PI3K inhibition, and macrophage Co-IP/ChIP

    PMID:24316979 PMID:24336331

    Open questions at the time
    • Full set of haploinsufficiency-relevant targets incomplete
    • NF-κB mechanism is Medium-confidence single lab
  14. 2014 High

    Established a non-transcriptional repair function, showing CUX1 CUT domains directly stimulate OGG1 to accelerate 8-oxoG base excision repair and prevent RAS-induced senescence.

    Evidence In vitro repair reconstitution with purified proteins, comet assays in Cux1+/- MEFs, and a transgenic mouse model

    PMID:24618719

    Open questions at the time
    • Structural basis of CUT domain-OGG1 stimulation undefined
  15. 2018 High

    Generalized the ancillary-repair mechanism to APE1, showing CUT domains stimulate APE1 activity and that CUX1 levels set abasic-site burden and chemoresistance in glioblastoma.

    Evidence In vitro repair assays with purified CUT domains and APE1, cell extract activity assays, and clonogenic survival with temozolomide

    PMID:29036362

    Open questions at the time
    • Whether CUT domains act on additional BER enzymes unknown
  16. 2017 Medium

    Showed a minimal two-CUT-domain fragment is sufficient for rapid recruitment to damage sites and radioprotection, isolating the repair function from full-length CUX1.

    Evidence CUT domain truncation, damage recruitment assays, OGG1 inhibition, and clonogenic survival

    PMID:28147323

    Open questions at the time
    • Recruitment mechanism to lesions not defined
  17. 2018 Low

    Linked radiation signaling to CUX1 processing, proposing CTSL-mediated p110 generation drives glioma EMT and invasion.

    Evidence Western blot of GSK-3β phosphorylation, CTSL gain/loss-of-function, processing assay, and invasion assays

    PMID:29331585

    Open questions at the time
    • Mechanistic claims rest largely on single-method Western blots
    • Causal chain from GSK-3β to CUX1 to EMT not established
  18. 2020 Medium

    Extended CUX1-NF-κB cooperation to a defined promoter motif, showing CUX1 is required for synergistic CXCL1-3 induction by TNF + IL-17A in synovial fibroblasts, and showed cathepsin L-generated p110 activates VEGF-D to promote angiogenesis.

    Evidence Silencing transcriptomics, siRNA, motif analysis, processing assays, and angiogenesis assays

    PMID:32079724 PMID:32388635

    Open questions at the time
    • Direct CUX1-p65 complex composition at chemokine promoters incompletely defined
  19. 2021 Medium

    Connected the repair and tumor-suppressor roles in hematopoiesis, showing CUX1 recruits EHMT2 to double-strand breaks for epigenetic repair and represses CFLAR, with haploinsufficiency creating apoptosis evasion and a targetable CFLAR vulnerability in AML.

    Evidence CUX1-deficient mouse HSPCs, ChIP for histone marks, gamma-H2AX/53BP1 assays, genome-wide CRISPR screen, CFLAR ChIP/reporter, and IAP antagonist treatment

    PMID:33931647 PMID:34473231

    Open questions at the time
    • Order of EHMT2 recruitment relative to other repair factors not fully resolved
    • CFLAR study single lab
  20. 2022 Medium

    Implicated CUX1 in vascular aging, showing it binds an atherosclerosis-associated SNP in the CDKN2A/B locus and triggers p16INK4a-dependent endothelial senescence.

    Evidence EMSA for SNP binding, reporter assays, gain/loss-of-function, and senescence assays

    PMID:37117763

    Open questions at the time
    • Genotype-specific effect on disease risk not directly tested in vivo

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the same CUT/homeodomain modules are partitioned between transcription and direct enzymatic stimulation of repair enzymes, and what dictates isoform- and context-specific activator-vs-repressor outputs, remains unresolved.
  • No structural model of CUT domain engagement with OGG1/APE1 or DNA
  • Determinants switching CUX1 between activation and repression undefined
  • Mechanism of recruitment to DNA damage sites not established

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 6 GO:0003677 DNA binding 5 GO:0098772 molecular function regulator activity 3
Localization
GO:0005634 nucleus 4 GO:0005654 nucleoplasm 3
Pathway
R-HSA-73894 DNA Repair 5 R-HSA-74160 Gene expression (Transcription) 5 R-HSA-1640170 Cell Cycle 3 R-HSA-162582 Signal Transduction 2 R-HSA-8953897 Cellular responses to stimuli 2
Partners
APE1CTSLE2F1EHMT2HDAC1OGG1RELATLE4

Evidence

Reading pass · 34 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2004 Cathepsin L, via isoforms devoid of a signal peptide that localize to the nucleus during G1-S transition, proteolytically processes CDP/Cux (CUX1) to generate the p110 isoform, thereby regulating cell cycle progression. Ectopic expression of cathepsin L, Cat L(-/-) knockout cells, immunofluorescence imaging, activity-based probes for nuclear cathepsin L localization, in situ processing assay Molecular cell High 15099520
2001 CDP/Cux (CUX1) DNA binding activity is up-regulated at G1/S transition by two events: dephosphorylation by Cdc25A phosphatase and proteolytic processing to generate the p110 isoform with stable DNA binding. Cell cycle synchronization, Western blot, EMSA, in vitro DNA binding assays Gene Medium 11403998
2001 Cyclin A-Cdk1 binds CDP/Cux (CUX1) via the Cut homeodomain and a downstream Cy motif, and phosphorylates serines 1237 and 1270, thereby inhibiting CDP/Cux DNA binding activity in G2 and preventing repression of the p21(WAF1) promoter. In vitro kinase/binding assays, site-directed mutagenesis (S1237A/S1270A), co-immunoprecipitation, cotransfection reporter assays, cell synchronization The Journal of biological chemistry High 11584018
2003 N-terminally truncated CDP/Cux isoforms (p110) act as transcriptional activators of the DNA polymerase alpha gene promoter in S phase, whereas full-length CDP/Cux does not; ChIP confirmed S-phase-specific promoter occupancy. Cotransfection reporter assays, retroviral expression, chromatin immunoprecipitation (ChIP), linker scanning analysis, in vitro DNA binding Molecular and cellular biology High 12665598
2002 The CDP/Cux p75 isoform, generated by transcription initiation within intron 20, contains only Cut repeat 3 and the homeodomain, binds DNA stably, represses the p21 promoter, and activates the DNA polymerase alpha promoter; aberrant expression in breast tumor cells promotes undifferentiated growth. Northern/Western blot characterization, reporter assays (repression/activation), stable cell line experiments (collagen tubulogenesis assay) Cancer research Medium 12438259
2006 A 90 kDa CDP/Cux isoform (p90) is generated by cathepsin L-mediated proteolytic processing, with its N-terminus between amino acids 918 and 938; p90 and p110 display similar DNA-binding and transcriptional activities. Deletion mutant mapping, co-expression with catalytically active cathepsin L isoforms lacking signal peptide, Western blot Biological chemistry Medium 16972798
2008 CUX1 (p110 isoform) and E2F1 co-occupy the promoters of Ect2, MgcRacGAP, and MKLP1 upon S-phase entry and cooperatively activate their transcription; CHR elements mediate G1 repression, and CUX1/E2F1 binding drives peak G2/M expression to coordinate cytokinesis. Chromatin immunoprecipitation (ChIP), promoter-luciferase reporter assays, dominant-negative and activated transcription factor expression, siRNA knockdown, Western blot Molecular and cellular biology High 19015243
2014 CUX1 functions as an ancillary factor in base excision repair by directly stimulating OGG1 enzymatic activity via its CUT domains, accelerating repair of 8-oxoG lesions; elevated CUX1 prevents RAS-induced senescence by reducing oxidative DNA damage. In vitro base excision repair assays with purified CUX1 and OGG1, single-cell gel electrophoresis (comet assay) in Cux1+/- MEFs and elevated-CUX1 cells, RAS-induced senescence assay, transgenic mouse model PLoS biology High 24618719
2018 CUX1 CUT domains stimulate APE1 (apurinic/apyrimidinic endonuclease 1) enzymatic activity in vitro; CUX1 knockdown decreases APE1 activity in cell extracts and increases abasic sites, while CUX1 overexpression has the opposite effect, promoting resistance to temozolomide. In vitro DNA repair assay with purified CUT domains and APE1, cell extract APE1 activity assay, abasic site quantification, CUX1 knockdown/overexpression in glioblastoma cells, clonogenic survival Neuro-oncology High 29036362
2017 A recombinant protein containing only two CUT domains of CUX1 is sufficient for rapid recruitment to DNA damage sites, acceleration of base excision repair, and increased cell survival following ionizing radiation. CUT domain truncation experiments, DNA damage recruitment assay, clonogenic survival assay, OGG1 inhibitor treatment Oncotarget Medium 28147323
2021 CUX1 recruits the histone methyltransferase EHMT2 to DNA double-strand breaks, promoting downstream H3K9 and H3K27 methylation, phosphorylated ATM retention, γH2AX focus formation and propagation, and 53BP1 recruitment, thereby mediating epigenetically driven DNA repair in hematopoietic stem and progenitor cells. CUX1-deficient mouse HSPCs, mechanistic epistasis analysis, γH2AX foci, 53BP1 recruitment assays, ChIP for histone marks at DNA breaks Blood Medium 34473231
2012 CUX1 (p110 isoform) modulates constitutive expression of ATM, ATR, and DNA damage response genes; CUX1 knockdown reduces ATM/ATR expression and impairs ATM autophosphorylation, Chk2/p53 phosphorylation, γH2AX and Rad51 foci, and DNA strand break repair after IR and UV. Genome-wide ChIP-chip (promoter arrays), RNAi knockdown, genetic inactivation, Western blot for phosphorylation markers, DNA damage foci immunofluorescence, clonogenic survival, cell cycle checkpoint analysis Nucleic acids research High 22319212
2013 CUX1 directly transcriptionally represses PIK3IP1 (a PI3K inhibitor); CUX1 deficiency leads to increased PI3K-AKT signaling and enhanced tumor growth, validating CUX1 as a tumor suppressor via the PI3K pathway. Transcriptional reporter assays, ChIP, Drosophila cancer models, mouse transposon insertional mutagenesis, PI3K/AKT inhibitor treatment of CUX1-mutant tumors Nature genetics High 24316979
2018 CUX1 knockdown in human CD34+ cells decreases expression of PIK3IP1 (PI3K inhibitor) and elevates PI3K/AKT signaling, promoting HSC exit from quiescence and proliferation leading to HSC exhaustion; restoration of CUX1 expression reverses MDS disease in mice. shRNA mouse models with graded CUX1 knockdown, bone marrow transplantation, RNA-sequencing, functional HSC quiescence assays, PI3K signaling pathway analysis Blood High 29592892
2021 CUX1 directly represses the CFLAR (FLIP) promoter; CUX1 haploinsufficiency de-represses CFLAR, driving apoptosis evasion in AML cells. Genome-wide CRISPR/Cas9 screening identified CFLAR as a selective vulnerability in CUX1-deficient AML. Genome-wide CRISPR/Cas9 loss-of-function screen, CFLAR promoter ChIP and reporter assays, CUX1 knockdown/KO in murine and human AML cells, IAP antagonist treatment Nature communications High 33931647
2022 CUX1 binds to an atherosclerosis-associated SNP (rs1537371) in the CDKN2A/B locus and regulates expression of p14ARF, p15INK4b, p16INK4a, and ANRIL in endothelial cells; CUX1 induction triggers p16INK4a-dependent replicative and stress-induced senescence. Electrophoretic mobility shift assay (EMSA) for SNP binding, reporter assays, CUX1 knockdown/overexpression, senescence assays (β-galactosidase, p16 expression) Nature aging Medium 37117763
2013 CUX1 interacts with NF-κB p65 and recruits HDAC1 to chemokine promoters (e.g., CXCL10), reducing NF-κB p65 acetylation at K310 and repressing NF-κB-regulated cytokines in tumor-associated macrophages, thereby modulating M1 polarization. Co-immunoprecipitation, DNA pulldown, chromatin immunoprecipitation (ChIP), NF-κB reporter assay, CUX1 overexpression/knockdown in macrophages Oncogene Medium 24336331
2020 CUX1 and NF-κB p65 co-mediate transcription of CXCL1, CXCL2, and CXCL3 from a unique CUX1-NF-κB binding motif in their promoters in synovial fibroblasts responding to TNF + IL-17A; CUX1 knockdown selectively abolishes this synergistic cytokine response. Gene-silencing transcriptomics, siRNA knockdown, promoter binding motif analysis, transcription factor independence assays (LIFR, STAT3, STAT4, ELF3 ruled out) Proceedings of the National Academy of Sciences of the United States of America Medium 32079724
2010 CUX1 (p110 and p75 isoforms) stimulates cell migration and invasion; siRNA knockdown of CUX1 reduces motility. CUX1 activates Snail and Slug transcription factors and cooperates with them to repress E-cadherin and occludin, disrupting cell-cell junctions. ChIP-chip identified >20 direct CUX1 target genes involved in cytoskeleton remodeling and Rho GTPase regulation. siRNA knockdown migration/invasion assays, ectopic expression experiments, ChIP-chip (promoter arrays), reporter assays for Snail/Slug/E-cadherin/occludin Cell adhesion & migration Medium 20224295
2010 CUX1 in neurons transcriptionally represses p27(Kip1) expression to regulate dendritic complexity; this effect requires the DNA-binding domains of CUX1 and is mediated downstream via RhoA. CUX1 overexpression and knockdown in cortical neurons, quantitative morphological analysis of dendrites, reporter assays, dominant-negative and activated RhoA epistasis experiments PloS one Medium 20485671
2010 Cux1 and Cux2 regulate dendrite branching, spine development, and synapse formation in layer II-III cortical neurons partly through direct transcriptional regulation of chromatin remodeling genes Xlr3b and Xlr4b; knockout mice show reduced synaptic function and working memory deficits. Cux1/Cux2 knockout mice, shRNA knockdown, morphological analysis, electrophysiology, behavioral testing, gene expression analysis Neuron High 20510857
2002 CDP/Cux C-terminus deletion (including the homeodomain) abolishes nuclear localization of the mutant protein and eliminates HiNF-D DNA binding activity in nuclear extracts; specific histone genes H4.1 and H1 containing CDP/Cux binding sites show reduced expression in homozygous mutant MEFs. Genetically targeted mouse (ΔC allele), indirect immunofluorescence, EMSA with nuclear extracts, Northern blot for histone genes Molecular and cellular biology Medium 11839809
1999 Cux/CDP is the identity component of NF-muNR and represses the immunoglobulin heavy chain intronic enhancer (Emu) by antagonizing the Bright transcription activator at matrix attachment regions (MARs), both at the DNA binding and functional levels. Expression library screening, EMSA supershift with Cux/CDP antiserum, cotransfection reporter assays, affinity-purified NF-muNR Western blot Molecular and cellular biology Medium 9858552
2009 Cux1 directly binds the p27(kip1) promoter in vivo and interacts with co-repressor Grg4 to enhance repression; ChIP assays show co-occupancy of Cux1, Grg4, HDAC1, and HDAC3 at two sites in the p27(kip1) promoter in newborn kidney tissue. Chromatin immunoprecipitation (ChIP) in kidney tissue, co-immunoprecipitation for Cux1-Grg4 interaction, promoter reporter (luciferase) assays, DNase I footprinting Gene High 19332113
2008 Sustained expression of p75-Cux1 isoform in transgenic mice causes polycystic kidneys; chromatin affinity purification confirmed direct binding of Cux1 to c-myc and p27 promoters, with upregulation of c-myc and downregulation of p27, increased cilia length, and elevated epithelial proliferation. Transgenic mouse model, chromatin affinity purification (ChAP), Western blot, immunohistochemistry, proliferation index The Journal of biological chemistry Medium 18356167
2004 SMAR1 and Cux/CDP physically interact with each other, co-localize in the perinuclear region, and independently repress the TCRbeta enhancer (Emu) via MARbeta; SMAR1 repressor activity is strongly enhanced in the presence of Cux/CDP. Overexpression of both proteins modulates chromatin structure at MARbeta as shown by DNase I hypersensitivity. Co-immunoprecipitation for SMAR1-Cux/CDP interaction, immunofluorescence colocalization, reporter gene cotransfection assays, DNase I hypersensitivity Nucleic acids research Medium 15371550
1997 CDP/Cut (CUX1) binds to a silencer element in the lactoferrin promoter (identified as a ~180 kDa protein by UV cross-linking/EMSA) in non-LF-expressing hematopoietic cells; CDP/cut overexpression blocks lactoferrin expression upon granulocyte colony-stimulating factor-induced neutrophil maturation. Luciferase reporter transfections, EMSA, UV cross-linking, Western blot identification, overexpression in myeloid stem cells Blood Medium 9326246
2020 Cathepsin L proteolytically processes CDP/Cux (CUX1) to produce the p110 isoform in gastric cancer; p110 then stably binds the VEGF-D promoter and activates VEGF-D transcription, promoting tumor angiogenesis. Western blot for p110 generation, co-immunoprecipitation of CTSL and CUX1, dual-luciferase reporter assay for VEGF-D promoter, endothelial tube formation/HUVEC migration, CAM assay Gastric cancer Medium 32388635
2018 Ionizing radiation reduces GSK-3β activity via CTSL-mediated phosphorylation of Ser9; CTSL also processes CUX1 to the p110 isoform, which then promotes EMT and increases glioma cell migration and invasion. Western blot for GSK-3β phosphorylation, CTSL overexpression/knockdown, CUX1 processing assay, migration/invasion assays Cellular signalling Low 29331585
2014 CUX1 and GLIS1 cooperate to stimulate TCF/β-catenin transcriptional activity and enhance cell migration and invasion; co-expression experiments in breast cancer model demonstrate their joint activation of Wnt pathway target genes. TCF/β-catenin reporter assay, co-expression experiments, Wnt inhibitor (FZD/LRP receptor inhibitors), laser-capture microdissection gene expression profiling Biology open Low 25217618
1992 Clox (mammalian CUX1/CDP) proteins are nuclear DNA-binding proteins with sequence specificity similar to Drosophila Cut; cotransfection experiments demonstrate they function as repressors of tissue-specific gene transcription. cDNA cloning, Western blot, EMSA, cotransfection transcription repression assays Development (Cambridge, England) Medium 1363085
2004 CUX1 in SVZ precursor cells shows nuclear localization in BrdU-positive dividing SVZ cells but weak diffuse localization in VZ cells, suggesting CUX1 function is first activated in SVZ intermediate progenitors. Immunofluorescence with anti-Cux-1 antibody, BrdU labeling, Pax-6 null mutation analysis The Journal of comparative neurology Low 15452856
2004 Cux-1 is significantly upregulated downstream of constitutively active Notch 1 signaling in rat kidney epithelial cells, and Cux1 interacts with the Groucho homolog TLE-4 co-repressor (which is recruited by Notch effector proteins), linking CUX1 to the Notch pathway. Constitutively active Notch 1 overexpression in RKE cells, Western blot, co-immunoprecipitation of Cux1 with TLE-4 Developmental dynamics Low 15499562
1997 Cux/CDP binds to the c-mos upstream enhancer site III via Cut repeat CR3 and the homeodomain (both required for efficient binding) and represses c-mos enhancer activity in cotransfection assays. GST-fusion protein pull-down with deletion mutants, EMSA supershift with anti-hCut antibodies, CAT reporter cotransfection assays Biochimica et biophysica acta Medium 9130595

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2019 CUT&Tag for efficient epigenomic profiling of small samples and single cells. Nature communications 1689 31036827
2008 MMEJ repair of double-strand breaks (director's cut): deleted sequences and alternative endings. Trends in genetics : TIG 736 18809224
2004 Expression of Cux-1 and Cux-2 in the subventricular zone and upper layers II-IV of the cerebral cortex. The Journal of comparative neurology 417 15452856
2005 Regulating cell migration: calpains make the cut. Journal of cell science 396 16129881
2019 Improved CUT&RUN chromatin profiling tools. eLife 393 31232687
2021 Single-cell CUT&Tag profiles histone modifications and transcription factors in complex tissues. Nature biotechnology 362 33846645
2020 Efficient low-cost chromatin profiling with CUT&Tag. Nature protocols 334 32913232
2004 A cathepsin L isoform that is devoid of a signal peptide localizes to the nucleus in S phase and processes the CDP/Cux transcription factor. Molecular cell 303 15099520
2022 Spatial-CUT&Tag: Spatially resolved chromatin modification profiling at the cellular level. Science (New York, N.Y.) 265 35143307
2010 Cux1 and Cux2 regulate dendritic branching, spine morphology, and synapses of the upper layer neurons of the cortex. Neuron 247 20510857
2012 Phosphatidylcholine and the CDP-choline cycle. Biochimica et biophysica acta 217 23010477
2001 Role of the multifunctional CDP/Cut/Cux homeodomain transcription factor in regulating differentiation, cell growth and development. Gene 201 11403998
2022 Genome-wide mapping of G-quadruplex structures with CUT&Tag. Nucleic acids research 152 34792172
2021 Single-cell CUT&Tag analysis of chromatin modifications in differentiation and tumor progression. Nature biotechnology 146 33846646
1995 Metabolism and actions of CDP-choline as an endogenous compound and administered exogenously as citicoline. Life sciences 144 7869846
2023 Genome editing of a rice CDP-DAG synthase confers multipathogen resistance. Nature 136 37316672
2019 Therapeutic targeting of circ-CUX1/EWSR1/MAZ axis inhibits glycolysis and neuroblastoma progression. EMBO molecular medicine 133 31709724
1998 Fission yeast cut mutations revisited: control of anaphase. Trends in cell biology 132 9695827
2012 CUX1 is a haploinsufficient tumor suppressor gene on chromosome 7 frequently inactivated in acute myeloid leukemia. Blood 129 23212519
2008 The multiple roles of CUX1: insights from mouse models and cell-based assays. Gene 127 18313863
1995 CDP-choline: pharmacological and clinical review. Methods and findings in experimental and clinical pharmacology 121 8709678
2005 Microtubules cut and run. Trends in cell biology 118 16126385
2013 Inactivating CUX1 mutations promote tumorigenesis. Nature genetics 109 24316979
2019 CUT&RUNTools: a flexible pipeline for CUT&RUN processing and footprint analysis. Genome biology 104 31500663
1992 Clox, a mammalian homeobox gene related to Drosophila cut, encodes DNA-binding regulatory proteins differentially expressed during development. Development (Cambridge, England) 104 1363085
1996 Switching from cut-and-paste to replicative Tn7 transposition. Science (New York, N.Y.) 102 8602527
2022 Multimodal chromatin profiling using nanobody-based single-cell CUT&Tag. Nature biotechnology 97 36536148
2014 CUX1, a haploinsufficient tumour suppressor gene overexpressed in advanced cancers. Nature reviews. Cancer 93 25190083
2002 Genetic ablation of the CDP/Cux protein C terminus results in hair cycle defects and reduced male fertility. Molecular and cellular biology 93 11839809
2007 The CDP-ethanolamine pathway and phosphatidylserine decarboxylation generate different phosphatidylethanolamine molecular species. The Journal of biological chemistry 89 17673461
2010 CUX1: target of Akt signalling and mediator of resistance to apoptosis in pancreatic cancer. Gut 87 20442202
2020 CDP-Diacylglycerol Synthases (CDS): Gateway to Phosphatidylinositol and Cardiolipin Synthesis. Frontiers in cell and developmental biology 86 32117988
2020 CUX1 and IκBζ (NFKBIZ) mediate the synergistic inflammatory response to TNF and IL-17A in stromal fibroblasts. Proceedings of the National Academy of Sciences of the United States of America 73 32079724
2017 Thymic Stromal Lymphopoietin: To Cut a Long Story Short. Cellular and molecular gastroenterology and hepatology 70 28275684
2021 Automated CUT&Tag profiling of chromatin heterogeneity in mixed-lineage leukemia. Nature genetics 69 34663924
1996 Primary structure, neural-specific expression, and chromosomal localization of Cux-2, a second murine homeobox gene related to Drosophila cut. The Journal of biological chemistry 69 8798433
1999 Cux/CDP homeoprotein is a component of NF-muNR and represses the immunoglobulin heavy chain intronic enhancer by antagonizing the bright transcription activator. Molecular and cellular biology 68 9858552
2012 CUX1 transcription factors: from biochemical activities and cell-based assays to mouse models and human diseases. Gene 65 22306263
1997 CDP-choline:1,2-diacylglycerol cholinephosphotransferase. Biochimica et biophysica acta 63 9370321
2003 CDP/Cux stimulates transcription from the DNA polymerase alpha gene promoter. Molecular and cellular biology 61 12665598
2021 p113 isoform encoded by CUX1 circular RNA drives tumor progression via facilitating ZRF1/BRD4 transactivation. Molecular cancer 60 34579723
2002 Characterization of a tissue-specific CDP/Cux isoform, p75, activated in breast tumor cells. Cancer research 60 12438259
2014 RAS transformation requires CUX1-dependent repair of oxidative DNA damage. PLoS biology 57 24618719
1997 CCAAT displacement protein (CDP/cut) recognizes a silencer element within the lactoferrin gene promoter. Blood 53 9326246
2010 The transcription factor Cux1 regulates dendritic morphology of cortical pyramidal neurons. PloS one 52 20485671
2019 Making the cut(s): how Cas12a cleaves target and non-target DNA. Biochemical Society transactions 51 31671185
2014 Cux1 and Cux2 selectively target basal and apical dendritic compartments of layer II-III cortical neurons. Developmental neurobiology 51 25059644
2021 CUT&RUNTools 2.0: a pipeline for single-cell and bulk-level CUT&RUN and CUT&Tag data analysis. Bioinformatics (Oxford, England) 50 34244724
2001 Phosphorylation of the CCAAT displacement protein (CDP)/Cux transcription factor by cyclin A-Cdk1 modulates its DNA binding activity in G(2). The Journal of biological chemistry 50 11584018
2018 Gene dosage effect of CUX1 in a murine model disrupts HSC homeostasis and controls the severity and mortality of MDS. Blood 46 29592892
2012 CUX1 transcription factor is required for optimal ATM/ATR-mediated responses to DNA damage. Nucleic acids research 45 22319212
2008 Cux-1 and Cux-2 control the development of Reelin expressing cortical interneurons. Developmental neurobiology 45 18327765
2004 Transcription and DNA adducts: what happens when the message gets cut off? DNA repair 45 15474416
2006 Expression of Cux-1 and Cux-2 in the developing somatosensory cortex of normal and barrel-defective mice. The anatomical record. Part A, Discoveries in molecular, cellular, and evolutionary biology 44 16419078
2008 CUX1 and E2F1 regulate coordinated expression of the mitotic complex genes Ect2, MgcRacGAP, and MKLP1 in S phase. Molecular and cellular biology 43 19015243
2014 Autocrine Activation of the Wnt/β-Catenin Pathway by CUX1 and GLIS1 in Breast Cancers. Biology open 40 25217618
2005 Isolation and characterization of murine Cds (CDP-diacylglycerol synthase) 1 and 2. Gene 40 16023307
2010 Glutamate receptor GRIA3--target of CUX1 and mediator of tumor progression in pancreatic cancer. Neoplasia (New York, N.Y.) 39 20689760
2021 AGPAT2 interaction with CDP-diacylglycerol synthases promotes the flux of fatty acids through the CDP-diacylglycerol pathway. Nature communications 38 34824276
2020 CDP-diacylglycerol, a critical intermediate in lipid metabolism. Chemistry and physics of lipids 38 32360136
2013 CUX1 modulates polarization of tumor-associated macrophages by antagonizing NF-κB signaling. Oncogene 38 24336331
2019 Distinct clinical and biological implications of CUX1 in myeloid neoplasms. Blood advances 36 31320321
2006 A novel proteolytically processed CDP/Cux isoform of 90 kDa is generated by cathepsin L. Biological chemistry 36 16972798
2004 SMAR1 and Cux/CDP modulate chromatin and act as negative regulators of the TCRbeta enhancer (Ebeta). Nucleic acids research 36 15371550
2017 Cut-and-Paste Transposons in Fungi with Diverse Lifestyles. Genome biology and evolution 35 29228286
2014 New Clox Systems for rapid and efficient gene disruption in Candida albicans. PloS one 35 24940603
2020 Cathepsin L promotes angiogenesis by regulating the CDP/Cux/VEGF-D pathway in human gastric cancer. Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association 34 32388635
2020 Circ-CUX1 Accelerates the Progression of Neuroblastoma via miR-16-5p/DMRT2 Axis. Neurochemical research 33 33000435
2002 Expression of N-terminally truncated isoforms of CDP/CUX is increased in human uterine leiomyomas. International journal of cancer 33 12115525
2000 The yeast CDP1 gene encodes a triple-helical DNA-binding protein. Nucleic acids research 33 11058104
2006 Cut and move: protein machinery for DNA processing in bacterial conjugation. Current opinion in structural biology 32 17079132
2004 A CDP-choline pathway for phosphatidylcholine biosynthesis in Treponema denticola. Molecular microbiology 32 14756787
2023 Phosphatidylethanolamine homeostasis under conditions of impaired CDP-ethanolamine pathway or phosphatidylserine decarboxylation. Frontiers in nutrition 31 36687696
2018 Cathepsin L promotes ionizing radiation-induced U251 glioma cell migration and invasion through regulating the GSK-3β/CUX1 pathway. Cellular signalling 31 29331585
1997 CDP-ethanolamine:1,2-diacylglycerol ethanolaminephosphotransferase. Biochimica et biophysica acta 31 9370323
2021 Making the cut with protease engineering. Cell chemical biology 30 34921772
2020 CUX1, A Controversial Player in Tumor Development. Frontiers in oncology 30 32547943
2004 Coexpression of Cux-1 and Notch signaling pathway components during kidney development. Developmental dynamics : an official publication of the American Association of Anatomists 30 15499562
2023 Cut&tag: a powerful epigenetic tool for chromatin profiling. Epigenetics 28 38105608
2018 The crux of Cux genes in neuronal function and plasticity. Brain research 28 29518378
2009 The homeodomain protein Cux1 interacts with Grg4 to repress p27 kip1 expression during kidney development. Gene 28 19332113
1997 Cux/CDP homeodomain protein binds to an enhancer in the rat c-mos locus and represses its activity. Biochimica et biophysica acta 28 9130595
2021 Cut-like homeobox 1 (CUX1) tumor suppressor gene haploinsufficiency induces apoptosis evasion to sustain myeloid leukemia. Nature communications 27 33931647
2023 Gene editing for dyslipidemias: New tools to "cut" lipids. Atherosclerosis 26 36725417
2018 Tailored Polyproteins Using Sequential Staple and Cut. Bioconjugate chemistry 25 29671584
2017 The DNA repair function of CUX1 contributes to radioresistance. Oncotarget 25 28147323
2008 Polycystic kidneys caused by sustained expression of Cux1 isoform p75. The Journal of biological chemistry 25 18356167
2018 CUX1 stimulates APE1 enzymatic activity and increases the resistance of glioblastoma cells to the mono-alkylating agent temozolomide. Neuro-oncology 24 29036362
2021 Identification of chromatin states during zebrafish gastrulation using CUT&RUN and CUT&Tag. Developmental dynamics : an official publication of the American Association of Anatomists 23 34647658
1996 CDP1, a novel Saccharomyces cerevisiae gene required for proper nuclear division and chromosome segregation. Genetics 23 8978028
2022 Post-GWAS functional analysis identifies CUX1 as a regulator of p16INK4a and cellular senescence. Nature aging 22 37117763
2021 Loss of a 7q gene, CUX1, disrupts epigenetically driven DNA repair and drives therapy-related myeloid neoplasms. Blood 22 34473231
2009 Moyamoya: to cut or not to cut is not the only question. A paediatric neurologist's perspective. Developmental medicine and child neurology 21 19895633
2022 Chemical inhibition of polyphenol oxidase and cut surface browning of fresh-cut apples. Critical reviews in food science and nutrition 20 35416745
2005 Differential expression of Cux-1 and p21 in polycystic kidneys from Pkd1 null and cpk mice. Kidney international 18 15673290
2025 DHODH modulates immune evasion of cancer cells via CDP-Choline dependent regulation of phospholipid metabolism and ferroptosis. Nature communications 17 40274823
2023 CUX1-related neurodevelopmental disorder: deep insights into phenotype-genotype spectrum and underlying pathology. European journal of human genetics : EJHG 17 37644171
2022 The significance of CUX1 and chromosome 7 in myeloid malignancies. Current opinion in hematology 17 35084368
2022 CDP-ribitol prodrug treatment ameliorates ISPD-deficient muscular dystrophy mouse model. Nature communications 17 35422047
2010 The roles of CUX1 homeodomain proteins in the establishment of a transcriptional program required for cell migration and invasion. Cell adhesion & migration 17 20224295

Missed literature

Know a paper Affinage missed for CUX1? Flag it for the maintainers and the community.

No submissions yet.