Affinage

CTBP1

C-terminal-binding protein 1 · UniProt Q13363

Length
440 aa
Mass
47.5 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: 8/9 claims corpus-supported (89%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CTBP1 is a bifunctional NAD(H)-sensing protein that operates as a nuclear transcriptional corepressor and as a cytoplasmic membrane-fission factor, coupling cellular metabolic state to gene expression and membrane trafficking (PMID:12805226, PMID:25652077). In the nucleus it is recruited to DNA-binding repressors through a hydrophobic cleft that recognizes PXDLS-type motifs, engaging transcription factors such as deltaEF1, SATB1, and Glis2 (PMID:10567582, PMID:19103759, PMID:16326862), and it assembles a core repressive machinery of HDAC1/2, CoREST/LSD1, and the SUMO E2 Ubc9, with HDAC activity contributing the bulk of repression (PMID:17967884). Repression depends on NAD(H)-dependent self-association: NAD(+) binding drives a dimer-to-tetramer transition through a Trp318 switch, and structural studies show the NAD(H)-free protein is conformationally destabilized at the dimer interface, whereas dehydrogenase catalysis itself is dispensable for repression (PMID:12805226, PMID:23940047, PMID:19351597). CtBP1 and CtBP2 act redundantly and dosage-sensitively to control developmental gene expression (PMID:12101226). In the cytoplasm CtBP1/BARS drives a dynamin-independent membrane-fission machinery for basolateral Golgi-to-plasma-membrane transport, post-Golgi carrier formation, and fluid-phase/macropinocytic endocytosis (PMID:15880102, PMID:18354494); the previously ascribed intrinsic LPAAT activity was shown to be a co-purification artefact (PMID:16319893). Fission is triggered by PAK1 phosphorylation at S147 upon EGF or viral stimulation (PMID:18354494, PMID:18323776), requires activation of phospholipase D1 (PMID:19322195), and proceeds via a trans-Golgi complex in which 14-3-3γ bridges CtBP1/BARS to PI(4)KIIIβ and CtBP1/BARS binds and activates LPAATδ to convert LPA to phosphatidic acid (PMID:22366688, PMID:27401954). Its activity across both compartments is tuned by post-translational modification—PKA, PAK1, and Akt1 phosphorylation, ADP-ribosylation that locks the dimer and blocks fission interactors, succinylation, and ubiquitination controlling stability and nuclear retention (PMID:23716697, PMID:18184656, PMID:20361981, PMID:29142217, PMID:36764210). At presynapses CtBP1 is anchored by Bassoon and Piccolo, and NAD/NADH-regulated shuttling between synaptic and nuclear pools, together with its PLD1-dependent fission activity, supports synaptic vesicle recycling (PMID:25652077, PMID:32075774). A de novo R342W mutation in the PXDLS-binding cleft impairs chromatin-factor binding and underlies a neurodevelopmental disorder with altered apoptotic responses in patient cells (PMID:31041561).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 1999 High

    Established CtBP1 as a sequence-specific corepressor recruited to DNA-binding factors, defining the PLDLS-motif recognition principle that organizes its nuclear function.

    Evidence Yeast two-hybrid, co-IP, and Gal4 repression assays with deltaEF1 and PLDLSL mutagenesis

    PMID:10567582

    Open questions at the time
    • Did not resolve the enzymatic core of the repressor complex
    • No structural basis for motif recognition yet
  2. 2002 High

    Demonstrated that Ctbp1 and Ctbp2 are functionally redundant, dosage-sensitive regulators of developmental gene expression in vivo.

    Evidence Mouse knockout epistasis and cell-based transcription assays

    PMID:12101226

    Open questions at the time
    • Did not assign distinct molecular roles to CtBP1 vs CtBP2
    • Specific target genes per process not fully mapped
  3. 2003 High

    Provided the structural basis for CtBP1's bifunctionality by showing NAD(H)-dependent dimerization and a defined PXDLS peptide-binding interface.

    Evidence X-ray crystallography of NAD(H) and PXDLS-peptide complexes with mutagenesis

    PMID:12805226

    Open questions at the time
    • Did not resolve the higher-order tetramer
    • Link between dimerization and membrane fission not yet mechanistic
  4. 2005 High

    Placed CtBP1/BARS as a dynamin-independent membrane-fission machine in selective trafficking routes and refuted its proposed intrinsic LPAAT activity.

    Evidence RNAi, dominant-negative, EM, transport assays; in vitro LPAAT reconstitution controls

    PMID:15880102 PMID:16319893

    Open questions at the time
    • Mechanism of fission without intrinsic acyltransferase activity left open
    • Trigger and partners for fission not yet identified
  5. 2007 High

    Resolved the architecture of the repressor complex, showing the PLDLS cleft as the recruitment hub for HDAC1/2, CoREST/LSD1, and Ubc9, with dimerization rather than catalysis required for repression.

    Evidence Structure-guided mutagenesis, co-IP, and transcriptional repression assays

    PMID:17967884

    Open questions at the time
    • In vivo stoichiometry of the assembled complex not defined
    • Context-specific subunit composition unresolved
  6. 2007 Medium

    Connected the nuclear repressor function to metabolic output by showing ADP-ribosylation inactivates repression and controls neutral lipid storage genes.

    Evidence siRNA, BFA treatment, ribosylation inhibitors, lipid droplet imaging, knockout MEFs

    PMID:17538025

    Open questions at the time
    • Direct target genes driving lipid storage not fully enumerated
    • Single-lab phenocopy of BFA effect
  7. 2008 High

    Identified PAK1 phosphorylation at S147 as the switch that activates CtBP1/BARS for macropinocytic-cup fission downstream of receptor and viral signaling.

    Evidence Phospho-site mutagenesis, live imaging, RNAi, and viral entry assays (two independent studies)

    PMID:18323776 PMID:18354494

    Open questions at the time
    • Upstream kinase activation kinetics in physiological contexts incomplete
    • How phosphorylation alters CtBP1 conformation/partner binding not structurally resolved
  8. 2009 High

    Defined the biochemical fission mechanism by establishing CtBP1/BARS as a physiological activator of PLD1 upstream of macropinosome formation.

    Evidence Co-IP, in vitro and intact-cell PLD assays, and 1-butanol inhibition

    PMID:19322195

    Open questions at the time
    • Spatial coordination of PLD1 product with fission site not fully resolved
    • Synergy with ARF GTPases mechanistically incomplete
  9. 2009 High

    Clarified the NAD(H)-coupled conformational logic, showing the apo mutant is destabilized at the dimer interface.

    Evidence Crystallography of NAD(H)-free G172E mutant with size-exclusion chromatography

    PMID:19351597

    Open questions at the time
    • Dynamics of NAD(H) sensing in cells not measured
    • Coupling to tetramerization not addressed structurally
  10. 2012 High

    Built the trans-Golgi fission complex by showing 14-3-3γ dimers bridge CtBP1/BARS to PI(4)KIIIβ under kinase control.

    Evidence Reciprocal co-IP, dominant-negative/RNAi disruption, live imaging, and EM

    PMID:22366688

    Open questions at the time
    • Lipid-modifying step downstream of complex assembly not yet defined
    • Quantitative phosphorylation dependence incomplete
  11. 2013 High

    Showed multimerization proceeds via a dimer intermediate to a tetramer governed by a Trp318 switch, decoupling repression from NAD catalysis.

    Evidence In vitro assembly, co-IP, mammalian two-hybrid, and reporter assays with mutagenesis

    PMID:23940047

    Open questions at the time
    • Functional role of the tetramer vs dimer in vivo not separated
    • Whether tetramerization gates specific target genes unknown
  12. 2013 High

    Defined a two-step CD38/BFA ADP-ribosylation mechanism that locks CtBP1/BARS as a dimer, blocking fission interactors and arresting mitotic Golgi partitioning.

    Evidence Mass spectrometry, ADP-ribosylation assays, mutagenesis, and cell-cycle analysis

    PMID:23716697

    Open questions at the time
    • Physiological inducers of this modification beyond BFA unclear
    • Reversal/turnover of the modification not characterized
  13. 2016 High

    Completed the lipid-conversion arm of fission by identifying LPAATδ activation by CtBP1/BARS to convert LPA to phosphatidic acid at post-Golgi carriers.

    Evidence Co-IP, in vitro acyltransferase assay, RNAi rescue, transport assays, and lipidomics

    PMID:27401954

    Open questions at the time
    • How PA generation mechanically drives scission not fully resolved
    • Selectivity for post-Golgi vs other membranes incomplete
  14. 2015 High

    Extended CtBP1 to neurons, showing active-zone anchoring by Bassoon/Piccolo and NAD/NADH-regulated synaptic-nuclear shuttling that couples activity to gene expression.

    Evidence Co-IP, live imaging, fractionation, NAD/NADH manipulation, and knockdown

    PMID:25652077

    Open questions at the time
    • Quantitative coupling of activity to nuclear target genes not mapped
    • Single-lab interaction data
  15. 2020 High

    Dissected neuronal CtBP1 into separable pools, assigning synaptic vesicle recycling to synaptic CtBP1 via PLD1 and synaptogenesis/release to nuclear CtBP1.

    Evidence Knockout neurons with targeted rescue constructs, electrophysiology, and live imaging

    PMID:32075774

    Open questions at the time
    • Molecular details of fission at the synaptic vesicle membrane incomplete
    • Coordination between the two pools during sustained activity unclear
  16. 2019 Medium

    Linked CTBP1 to human disease by showing the de novo R342W cleft mutation impairs chromatin-factor binding and alters apoptotic gene programs.

    Evidence Unbiased co-IP/MS, RNA-seq, and patient fibroblast glucose-deprivation assays

    PMID:31041561

    Open questions at the time
    • Causal chain from mutation to neurodevelopmental phenotype incomplete
    • Single study

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the metabolic NAD(H) sensor, the post-translational modification code, and partner-specific recruitment are integrated to switch CtBP1 between nuclear repression and cytoplasmic/synaptic fission in a given cellular context remains unresolved.
  • No unified model coupling oligomeric state to compartmental function in vivo
  • Context-specific determinants of partner choice unknown
  • Quantitative thresholds of NADH/NAD+ governing the switch undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 4 GO:0003677 DNA binding 2 GO:0060090 molecular adaptor activity 2 GO:0098772 molecular function regulator activity 2
Localization
GO:0005634 nucleus 3 GO:0005794 Golgi apparatus 3 GO:0005829 cytosol 2 GO:0005886 plasma membrane 2
Pathway
R-HSA-4839726 Chromatin organization 3 R-HSA-5653656 Vesicle-mediated transport 3 R-HSA-74160 Gene expression (Transcription) 3 R-HSA-112316 Neuronal System 2 R-HSA-5357801 Programmed Cell Death 2
Partners
BASSOONEP300HDAC1HDAC2PAK1PICCOLOPLD1YWHAG
Complex memberships
CtBP1 corepressor complex (HDAC1/2, CoREST/LSD1, Ubc9)PRDM14-CtBP1/2-PRC2 complextrans-Golgi fission complex (14-3-3γ/PI4KIIIβ/LPAATδ)

Evidence

Reading pass · 38 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2003 Crystal structure of rat CtBP/BARS in binary complex with NAD(H) and ternary complex with a PXDLS peptide revealed that CtBP/BARS forms a NAD(H)-bound dimer; the peptide-binding site maps the recognition interface for DNA-binding proteins and histone deacetylases to an N-terminal region; site-directed mutagenesis supported the structural data and provided a molecular basis for the two co-existing activities (transcriptional co-repression and acyl-CoA-dependent membrane fission). X-ray crystallography, site-directed mutagenesis, binding experiments The EMBO journal High 12805226
2007 Structure-based functional dissection of CtBP1 showed that the PLDLS-binding hydrophobic cleft is the primary recruitment center for DNA-binding repressors and for the core enzymatic components HDAC1/2, CoREST/LSD1, and Ubc9 (E2 SUMO ligase), which interact via non-PLDLS contacts. HDACs contribute predominantly to CtBP1 repression activity. NAD(H)-dependent dimerization (not dehydrogenase activity) is required for transcriptional repression. CtBP1 also serves as a platform for sumoylation of cofactors. Auxiliary components (G9a/Wiz/CDYL HMTase complex, PIAS1, HPC2) interact with the PLDLS cleft and are displaced by E1A-PLDLS. Structure-based mutagenesis, co-immunoprecipitation, transcriptional repression assays Molecular and cellular biology High 17967884
2013 NAD(H)-dependent multimerization of CtBP1 proceeds through a dimeric intermediate to a tetramer; Trp318 acts as a switch for dimerization upon NAD(+) binding; the C-terminus is required for dimer-of-dimers formation. NAD(H)-binding mutants do not self-associate in vitro or in vivo but retain PXDLS-motif binding. Transcriptional repression depends on the N-terminal domain recruiting PXDLS-containing targets, not on NAD binding or dehydrogenase activity per se. In vitro biochemical oligomerization assays, co-immunoprecipitation, mammalian two-hybrid, mutagenesis, transcriptional reporter assays The Journal of biological chemistry High 23940047
2005 CtBP3/BARS (the short isoform of CtBP1) controls membrane fission in basolateral transport from the Golgi to the plasma membrane and in fluid-phase endocytosis, but is inactive in apical transport and receptor-mediated endocytosis (both controlled by dynamin), establishing that CtBP1/BARS and dynamin define distinct, non-overlapping fission machineries. Dominant-negative protein expression, RNAi, live-cell and electron microscopy, transport assays in intact cells Nature cell biology High 15880102
2005 The proposed lysophosphatidic acid acyltransferase (LPAAT) activity of CtBP/BARS, previously suggested to drive membrane fission by changing bilayer curvature, was shown to be a co-purification artefact; purified CtBP/BARS has no intrinsic LPAAT activity. In vitro LPAAT enzymatic assay with purified proteins and appropriate controls Nature High 16319893
2008 Upon EGF receptor activation, CtBP1/BARS translocates to macropinocytic cups, is phosphorylated by PAK1 at a specific serine residue (identified as the PAK substrate site), and this phosphorylation is essential for fission of the macropinocytic cup; CtBP1/BARS is also required for echovirus 1 macropinocytic internalization. Live-cell fluorescence microscopy, pharmacological inhibition, phosphorylation site mutagenesis, RNAi, viral infection assay The EMBO journal High 18354494
2008 Ad3 infectious macropinocytosis requires viral activation of PAK1, which phosphorylates CtBP1 at S147; a phosphorylation-defective S147A-CtBP1 mutant blocks Ad3 but not Ad5 infection, directly linking PAK1 phosphorylation of CtBP1 to Ad3 macropinocytic entry. Dominant-negative mutant overexpression, pharmacological inhibition, viral infection assays, co-localization microscopy The EMBO journal High 18323776
2009 CtBP1/BARS is a physiological activator of phospholipase D1 (PLD1); EGF or serum stimulation induces association of CtBP1/BARS with PLD1, and CtBP1/BARS activates PLD1 synergistically with ARF GTPases in vitro and in cells. 1-Butanol (PLD product inhibitor) blocks EGF-induced macropinocytosis, placing CtBP1/BARS–PLD1 activation upstream of macropinosome formation. Co-immunoprecipitation, in vitro PLD activity assay, intact-cell PLD assay, pharmacological inhibition The EMBO journal High 19322195
2012 14-3-3γ dimers bridge CtBP1-S/BARS with PI(4)KIIIβ to form a complex that couples Golgi carrier budding and fission; the complex is stabilized by PKD and PAK phosphorylation, and disrupting CtBP1-S/BARS association with 14-3-3γ or PI(4)KIIIβ inhibits fission of elongating post-Golgi carrier precursors. Co-immunoprecipitation, dominant-negative constructs, RNAi, live-cell imaging, electron microscopy Nature cell biology High 22366688
2013 BFA induces ADP-ribosylation of CtBP1-S/BARS via a two-step mechanism: CD38 (ADP-ribosyl cyclase) synthesizes a BFA-ADP-ribose conjugate, which then covalently inserts into the CtBP1-S/BARS NAD(+)-binding pocket. This locks CtBP1-S/BARS in a dimer conformation, prevents binding to membrane fission interactors, and inhibits mitotic Golgi partitioning, arresting cells in G2. Mass spectrometry, biochemical ADP-ribosylation assays, mutagenesis, cell-cycle analysis, co-immunoprecipitation Proceedings of the National Academy of Sciences of the United States of America High 23716697
2016 When incorporated into the 14-3-3γ/PI4KIIIβ/ARF/PKD/PAK complex at the trans-Golgi, CtBP1-S/BARS binds to and activates LPA acyltransferase δ (LPAATδ), converting LPA to phosphatidic acid (PA); this LPA-to-PA conversion is essential for fission of post-Golgi carriers. Co-immunoprecipitation, in vitro acyltransferase activity assay, RNAi, transport assays, lipidomics Nature communications High 27401954
2009 Crystal structure of the NAD(H)-free G172E CtBP1/BARS mutant reveals that absence of NAD(H) causes flexibility and backbone conformational changes at the dimerization interface and interdomain region, explaining how NAD(H) binding promotes functional dimerization. X-ray crystallography, size-exclusion chromatography Biochemical and biophysical research communications High 19351597
2007 Mono-ADP-ribosylation of CtBP1/BARS (induced by BFA) inactivates its transcriptional repressor function, leading to activation of genes that regulate neutral lipid storage; siRNA knockdown of CtBP1/BARS mimics BFA-induced lipid droplet loss, and CtBP1/BARS-deficient MEFs are defective in lipid accumulation. siRNA knockdown, BFA treatment, ribosylation inhibitors, lipid droplet microscopy, MEF knockout cells Molecular biology of the cell Medium 17538025
1999 CtBP1 (and CtBP2) acts as a corepressor of the zinc finger-homeodomain transcription factor deltaEF1; interaction is mediated by the PLDLSL sequence in deltaEF1; exogenous CtBP1/2 enhances deltaEF1-mediated transcriptional repression and this enhancement is abolished when the PLDLSL motif is mutated. Yeast two-hybrid, co-immunoprecipitation, Gal4-fusion transcriptional repression assays, mutagenesis Molecular and cellular biology High 10567582
2008 SATB1 interacts with CtBP1 via the PVPLS motif within SATB1's PDZ-like domain to form a repressor complex in vivo; acetylation of SATB1 (induced by LiCl/ionomycin) disrupts its association with CtBP1, leading to derepression of target genes (IL-2, c-Myc promoters) and reduced CtBP1 and HDAC1 chromatin occupancy. Co-immunoprecipitation, chromatin immunoprecipitation, gene expression profiling, mutagenesis Molecular and cellular biology High 19103759
2008 PKA (activated by ACTH/cAMP signaling) phosphorylates CtBP1 at T144, stimulating partnering of CtBP1 with CtBP2 and modulating ACTH-dependent CYP17 transcription; both ACTH/cAMP signaling and NADH/NAD+ ratio changes drive nuclear-cytoplasmic oscillation of CtBP proteins. Phosphorylation site mutagenesis, co-immunoprecipitation, transcriptional reporter assays, pharmacological manipulation of cAMP The Journal of biological chemistry Medium 18184656
2010 Akt1 phosphorylates CtBP1 (promoted by the SUMO E3 ligase Pc2/Cbx4 which recruits Akt1 and prevents its dephosphorylation); Akt1-mediated phosphorylation of CtBP1 decreases its dimerization, targets it for poly-ubiquitylation and proteasomal degradation, and reduces transcriptional repression. Co-immunoprecipitation, phospho-specific analysis, mutagenesis (phosphomimetic), ubiquitylation assay, stability assays, transcriptional reporter Journal of molecular biology Medium 20361981
2017 FBXO32 (an E3 ubiquitin ligase) directly ubiquitinates CtBP1, which is required for CtBP1 stability and nuclear retention; this ubiquitination is essential for epigenetic remodeling and transcriptional induction of CtBP1 target genes that create a microenvironment permissive for EMT. Co-immunoprecipitation, ubiquitination assay, nuclear fractionation, ChIP, siRNA knockdown, xenograft model Nature communications Medium 29142217
2015 CtBP1 is present in both presynaptic and nuclear pools of neurons; it is anchored to presynapses by direct interaction with active zone scaffolding proteins Bassoon and Piccolo; synaptic retention and nuclear shuttling of CtBP1 are co-regulated by neuronal activity via modulation of cellular NAD/NADH levels, thereby coupling presynaptic activity to nuclear gene expression. Co-immunoprecipitation, live-cell imaging, subcellular fractionation, NAD/NADH manipulation, knockdown experiments The EMBO journal High 25652077
2020 Presynaptic CtBP1 facilitates compensatory endocytosis of synaptic vesicles via its membrane-fission activity; in CtBP1-null hippocampal neurons, recycling of synaptic vesicles is impaired. Rescue experiments with targeted constructs showed that while synaptogenesis and release probability are controlled by nuclear CtBP1, efficient SV recycling depends on synaptic CtBP1 and requires activation of PLD1. Knockout neurons, targeted rescue constructs, electrophysiology, live-cell fluorescence imaging Cell reports High 32075774
2009 CtBP1 represses Brca1 transcription by binding to the E2F4 site of the Brca1 promoter in a redox-dependent manner: CtBP1 recruitment is increased at high NADH levels (hypoxic conditions), and pharmacological reduction of NADH with Tempol relieves CtBP1-mediated Brca1 repression and increases DNA repair. Chromatin immunoprecipitation, reporter assay, NADH manipulation, siRNA knockdown, tissue array immunostaining Oncogene Medium 20818429
2009 Agonist-bound ERalpha recruits the corepressor CtBP1 (via p300, a p300-interacting partner) to early estrogen-repressed genes, driving chromatin modifications leading to transcriptional repression; p300 knockdown prevents estrogen-mediated gene repression. Chromatin immunoprecipitation, siRNA knockdown, gene expression analysis Molecular and cellular biology Medium 19188451
2014 ZNF750 interacts with chromatin regulators RCOR1, KDM1A, and CTBP1/2 through conserved PLNLS sequences; KDM1A colocalizes with ZNF750 at progenitor genes to facilitate their repression, while KLF4 colocalizes at differentiation genes for activation; CTBP1/2 and RCOR1 participate in both regulatory modes. Co-immunoprecipitation, ChIP-seq, gene depletion (RNAi) Genes & development Medium 25228645
2010 Bcl3 interacts with CtBP1 via a PXDLS/R motif embedded in Bcl3, stabilizing CtBP1 by blocking proteasome-dependent degradation; this stabilization sustains CtBP1-mediated repression of pro-apoptotic genes and inhibits apoptosis. Proteomic (co-IP/MS), co-immunoprecipitation, proteasome inhibitor assay, apoptosis assay Biochemical and biophysical research communications Medium 20800578
2019 The pathogenic de novo R342W CtBP1 mutation (located in the PLDLS-binding cleft) reduces interaction with several chromatin-modifying factors as shown by unbiased proteomics; genome-wide transcriptome changes occur in cells expressing the mutant; patient-derived fibroblasts show enhanced apoptosis during glucose deprivation linked to upregulation of NOXA. Unbiased proteomic (co-IP/MS), RNA-seq, patient-derived fibroblast functional assays Neurogenetics Medium 31041561
2013 FANCC (Fanconi anemia group C protein) and other FA core complex proteins interact directly with CtBP1; CtBP1 is essential for proliferation, cell survival, and chromosomal integrity in FA cells; expression profiling of CtBP1-depleted and FA-depleted cells identified commonly regulated genes including the Wnt antagonist DKK1. Co-immunoprecipitation, siRNA knockdown, expression profiling Blood Medium 23303816
2012 CtBP1 interacts with Ikaros isoforms in pituitary tumor cells; CtBP1 deficiency up-regulates Sprouty2 and down-regulates Enpp2; CtBP1-deficient pituitary cells are more susceptible to hypoxia-induced apoptosis, rescued by Enpp2-derived lysophosphatidic acid treatment. Co-immunoprecipitation, siRNA knockdown, apoptosis assay, pharmacological rescue Molecular endocrinology Medium 22301782
2019 CtBP1 directly interacts with transcription factor FOXO3a and histone acetyltransferase p300 in vivo and in vitro; the CtBP1-p300-FOXO3a transcriptional complex specifically binds to the promoters of the pro-apoptotic genes Bax and Bim and represses their expression in osteosarcoma cells. Co-immunoprecipitation, GST pulldown, ChIP, promoter reporter assay, microarray Journal of cellular physiology Medium 31074088
2019 The CtBP1-HDAC1/2-IRF1 transcriptional complex binds to the GAS5 promoter and represses its expression in osteosarcoma cells; identified by co-IP/mass spectrometry and confirmed by co-IP assays. Co-immunoprecipitation, mass spectrometry, ChIP, siRNA knockdown International journal of biological sciences Medium 31337976
2023 KAT2A promotes succinylation of CtBP1 at K46 and K280, which suppresses CtBP1's inhibitory activity on CDH1 transcription; CtBP1 directly binds SP1 to repress CDH1 transcription, and this repression is attenuated by KAT2A-mediated succinylation. Co-immunoprecipitation, ChIP, succinylation site mutagenesis, promoter reporter assay, siRNA knockdown, xenograft Biochemical and biophysical research communications Medium 36764210
2018 ATM-mediated phosphorylation of EVI1 at C-terminal S858/S860 increases EVI1's association with CtBP1 under genotoxic stress; EVI1-AQA (phosphorylation mutant) shows profoundly impaired interaction with CtBP1 and reduced clonogenic potential, linking ATM signaling to CtBP1-dependent EVI1 function. Mass spectrometry phosphoproteomics, phospho-site mutagenesis, co-immunoprecipitation, clonogenic assay Nucleic acids research Medium 29939287
2002 Genetic analysis in mice showed that Ctbp1 and Ctbp2 have overlapping roles in regulating gene expression during development; mice harboring various combinations of Ctbp1 and Ctbp2 mutant alleles exhibit dosage-sensitive defects across a wide range of developmental processes, and transcription assays in CtBP-deficient cells confirm overlapping transcriptional regulatory functions. Mouse knockout genetics (epistasis), transcription assays in CtBP-deficient cells Molecular and cellular biology High 12101226
2014 NSC95397 inhibits the CtBP1–E1A (PXDLS motif) protein-protein interaction (IC50 = 2.9 µM) and disrupts CtBP1-mediated transcriptional repression of a target gene; NSC95397 acts as a weak substrate of CtBP1 dehydrogenase activity, indicating it engages the active site. AlphaScreen HTS assay, secondary biochemical assays, transcriptional reporter assay Journal of biomolecular screening Medium 25477201
2020 CTBP1 activates RAD51 transcription in breast cancer cells; CtBP1 depletion increases cancer cell sensitivity to cisplatin, and re-expression of exogenous RAD51 in CtBP1-depleted cells restores cisplatin resistance, placing CtBP1 upstream of RAD51-mediated DNA repair in resistance. shRNA knockdown, chromatin immunoprecipitation, dual-luciferase reporter assay, cisplatin sensitivity assay Molecular carcinogenesis Medium 32124501
2020 CTBP1 forms a repressor complex with ZEB1, EP300, and HDACs on the CLCA2 promoter to repress CLCA2 expression in prostate cancer cells; CLCA2 promotes cell adhesion and inhibits EMT; this repression is linked to metabolic syndrome/high-fat diet conditions. ChIP, co-immunoprecipitation, promoter reporter assay, siRNA knockdown, xenograft model International journal of cancer Medium 29536528
2005 CtBP1 physically interacts with Glis2 transcription factor (confirmed by GST pulldown); co-expression of CtBP1 with Glis2 relocalizes CtBP1 from diffuse cytoplasmic/nuclear distribution to nuclear speckles co-localizing with Glis2; CtBP1 recruits HDAC3 to mediate Glis2-dependent transcriptional repression. Yeast two-hybrid, GST pulldown, mammalian two-hybrid, confocal microscopy, transcriptional reporter assay Nucleic acids research Medium 16326862
2020 The PRDM14-CtBP1/2-PRC2 complex mediates transcriptional repression during transition from primed to naïve pluripotency; CtBP1/2 bind PRDM14 through CBFA2T2; loss of Ctbp1/2 impairs PRDM14-mediated repression and reduces PRC2/H3K27me3 enrichment at target genes. Co-immunoprecipitation, ChIP-seq, knockout cells, transcriptional analysis Journal of cell science Medium 32661086
2023 CTBP1 interacts with HDAC1 and HDAC2 to form a complex that suppresses MAT1A transcription in hepatocellular carcinoma cells; MAT1A suppression reduces S-adenosylmethionine levels, promoting ferroptosis resistance and immune escape. Co-immunoprecipitation, ChIP, siRNA knockdown, S-adenosylmethionine measurement, xenograft Laboratory investigation Medium 37230466

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 Overlapping and unique roles for C-terminal binding protein 1 (CtBP1) and CtBP2 during mouse development. Molecular and cellular biology 255 12101226
2013 Androgen-responsive long noncoding RNA CTBP1-AS promotes prostate cancer. The EMBO journal 230 23644382
2009 C/EBPalpha and the corepressors CtBP1 and CtBP2 regulate repression of select visceral white adipose genes during induction of the brown phenotype in white adipocytes by peroxisome proliferator-activated receptor gamma agonists. Molecular and cellular biology 167 19564408
2008 Subversion of CtBP1-controlled macropinocytosis by human adenovirus serotype 3. The EMBO journal 165 18323776
2008 The closure of Pak1-dependent macropinosomes requires the phosphorylation of CtBP1/BARS. The EMBO journal 157 18354494
2005 CtBP3/BARS drives membrane fission in dynamin-independent transport pathways. Nature cell biology 144 15880102
2003 CtBP/BARS: a dual-function protein involved in transcription co-repression and Golgi membrane fission. The EMBO journal 135 12805226
2014 ZNF750 interacts with KLF4 and RCOR1, KDM1A, and CTBP1/2 chromatin regulators to repress epidermal progenitor genes and induce differentiation genes. Genes & development 121 25228645
2002 The cell morphogenesis gene ANGUSTIFOLIA encodes a CtBP/BARS-like protein and is involved in the control of the microtubule cytoskeleton. The EMBO journal 118 11889034
1999 Identification of CtBP1 and CtBP2 as corepressors of zinc finger-homeodomain factor deltaEF1. Molecular and cellular biology 116 10567582
2007 Role of the PLDLS-binding cleft region of CtBP1 in recruitment of core and auxiliary components of the corepressor complex. Molecular and cellular biology 105 17967884
2006 The multiple activities of CtBP/BARS proteins: the Golgi view. Trends in cell biology 102 16483777
2017 The Role of CtBP1 in Oncogenic Processes and Its Potential as a Therapeutic Target. Molecular cancer therapeutics 81 28576945
2005 Endophilin and CtBP/BARS are not acyl transferases in endocytosis or Golgi fission. Nature 77 16319893
2011 Evolution: On a bender--BARs, ESCRTs, COPs, and finally getting your coat. The Journal of cell biology 74 21670211
2012 A 14-3-3γ dimer-based scaffold bridges CtBP1-S/BARS to PI(4)KIIIβ to regulate post-Golgi carrier formation. Nature cell biology 72 22366688
2016 Golgi membrane fission requires the CtBP1-S/BARS-induced activation of lysophosphatidic acid acyltransferase δ. Nature communications 62 27401954
1998 A novel C-terminal binding protein (CTBP2) is closely related to CTBP1, an adenovirus E1A-binding protein, and maps to human chromosome 21q21.3. Genomics 62 9479502
2012 Role of transcriptional corepressor CtBP1 in prostate cancer progression. Neoplasia (New York, N.Y.) 61 23097625
2008 Acetylation-dependent interaction of SATB1 and CtBP1 mediates transcriptional repression by SATB1. Molecular and cellular biology 59 19103759
2017 FBXO32 promotes microenvironment underlying epithelial-mesenchymal transition via CtBP1 during tumour metastasis and brain development. Nature communications 58 29142217
2009 Estrogen receptor alpha represses transcription of early target genes via p300 and CtBP1. Molecular and cellular biology 56 19188451
2015 Synaptic activity controls localization and function of CtBP1 via binding to Bassoon and Piccolo. The EMBO journal 53 25652077
2007 Involvement of CtBP1 in the transcriptional activation of the MDR1 gene in human multidrug resistant cancer cells. Biochemical pharmacology 52 17662696
2016 The miR-644a/CTBP1/p53 axis suppresses drug resistance by simultaneous inhibition of cell survival and epithelial-mesenchymal transition in breast cancer. Oncotarget 49 27409664
2022 Dendrimers as nanoscale vectors: Unlocking the bars of cancer therapy. Seminars in cancer biology 46 35700939
2009 CtBP1/BARS is an activator of phospholipase D1 necessary for agonist-induced macropinocytosis. The EMBO journal 44 19322195
2011 Transcriptional down-regulation of Brca1 and E-cadherin by CtBP1 in breast cancer. Molecular carcinogenesis 43 21681822
2020 LncRNA CTBP1-AS2 alleviates high glucose-induced oxidative stress, ECM accumulation, and inflammation in diabetic nephropathy via miR-155-5p/FOXO1 axis. Biochemical and biophysical research communications 39 32868076
2010 Bcl3-dependent stabilization of CtBP1 is crucial for the inhibition of apoptosis and tumor progression in breast cancer. Biochemical and biophysical research communications 39 20800578
2010 Redox-dependent Brca1 transcriptional regulation by an NADH-sensor CtBP1. Oncogene 38 20818429
2022 LncRNA CTBP1-DT-encoded microprotein DDUP sustains DNA damage response signalling to trigger dual DNA repair mechanisms. Nucleic acids research 37 35849344
2023 The DDUP protein encoded by the DNA damage-induced CTBP1-DT lncRNA confers cisplatin resistance in ovarian cancer. Cell death & disease 36 37633920
2013 Molecular mechanism and functional role of brefeldin A-mediated ADP-ribosylation of CtBP1/BARS. Proceedings of the National Academy of Sciences of the United States of America 36 23716697
2007 Sensory properties of meal replacement bars and beverages made from whey and soy proteins. Journal of food science 34 17995701
2019 Sp1-induced LncRNA CTBP1-AS2 is a novel regulator in cardiomyocyte hypertrophy by interacting with FUS to stabilize TLR4. Cardiovascular pathology : the official journal of the Society for Cardiovascular Pathology 33 31220774
2014 Androgen Receptor Coregulator CTBP1-AS Is Associated With Polycystic Ovary Syndrome in Chinese Women: A Preliminary Study. Reproductive sciences (Thousand Oaks, Calif.) 33 25552498
2013 Nicotinamide adenine dinucleotide-induced multimerization of the co-repressor CtBP1 relies on a switching tryptophan. The Journal of biological chemistry 33 23940047
2013 Components of the CtBP1/BARS-dependent fission machinery. Histochemistry and cell biology 33 23996193
2023 Date Palm Fruit (Phoenix dactylifera) and Its Promising Potential in Developing Functional Energy Bars: Review of Chemical, Nutritional, Functional, and Sensory Attributes. Nutrients 32 37432292
2014 Prostate tumor growth is impaired by CtBP1 depletion in high-fat diet-fed mice. Clinical cancer research : an official journal of the American Association for Cancer Research 31 24842953
2014 Small Molecule, NSC95397, Inhibits the CtBP1-Protein Partner Interaction and CtBP1-Mediated Transcriptional Repression. Journal of biomolecular screening 31 25477201
2005 Krüppel-like zinc finger protein Gli-similar 2 (Glis2) represses transcription through interaction with C-terminal binding protein 1 (CtBP1). Nucleic acids research 31 16326862
2018 MicroRNA485-3p negatively regulates the transcriptional co-repressor CtBP1 to control the oncogenic process in osteosarcoma cells. International journal of biological sciences 30 30262996
2018 Clinical significance of long noncoding RNA VIM-AS1 and CTBP1-AS2 expression in type 2 diabetes. Journal of cellular biochemistry 30 30506719
2018 CLCA2 epigenetic regulation by CTBP1, HDACs, ZEB1, EP300 and miR-196b-5p impacts prostate cancer cell adhesion and EMT in metabolic syndrome disease. International journal of cancer 29 29536528
2009 Hardening of high-protein nutrition bars and sugar/polyol-protein phase separation. Journal of food science 29 19723194
2013 CtBP1 is expressed in melanoma and represses the transcription of p16INK4a and Brca1. The Journal of investigative dermatology 28 23303449
2013 CtBP1 is involved in epithelial-mesenchymal transition and is a potential therapeutic target for hepatocellular carcinoma. Oncology reports 27 23756565
2007 Evidence that mono-ADP-ribosylation of CtBP1/BARS regulates lipid storage. Molecular biology of the cell 26 17538025
2020 LINC01426 contributes to clear cell renal cell carcinoma progression by modulating CTBP1/miR-423-5p/FOXM1 axis via interacting with IGF2BP1. Journal of cellular physiology 25 32583425
2008 Phosphorylation of CtBP1 by cAMP-dependent protein kinase modulates induction of CYP17 by stimulating partnering of CtBP1 and 2. The Journal of biological chemistry 25 18184656
2020 CtBP1 transactivates RAD51 and confers cisplatin resistance to breast cancer cells. Molecular carcinogenesis 24 32124501
2023 Out of the ESCPE room: Emerging roles of endosomal SNX-BARs in receptor transport and host-pathogen interaction. Traffic (Copenhagen, Denmark) 23 37089068
2020 CtBP1 promotes tumour-associated macrophage infiltration and progression in non-small-cell lung cancer. Journal of cellular and molecular medicine 23 32910558
2021 Targeting the CtBP1-FOXM1 transcriptional complex with small molecules to overcome MDR1-mediated chemoresistance in osteosarcoma cancer stem cells. Journal of Cancer 22 33391445
2021 Gastroblastoma with a novel EWSR1-CTBP1 fusion presenting in adolescence. Genes, chromosomes & cancer 22 34041825
2020 SP1-induced upregulation of lncRNA CTBP1-AS2 accelerates the hepatocellular carcinoma tumorigenesis through targeting CEP55 via sponging miR-195-5p. Biochemical and biophysical research communications 22 32988587
2019 The CtBP1-p300-FOXO3a transcriptional complex represses the expression of the apoptotic regulators Bax and Bim in human osteosarcoma cells. Journal of cellular physiology 22 31074088
2013 Fanconi anemia proteins interact with CtBP1 and modulate the expression of the Wnt antagonist Dickkopf-1. Blood 22 23303816
2023 Succinylation of CTBP1 mediated by KAT2A suppresses its inhibitory activity on the transcription of CDH1 to promote the progression of prostate cancer. Biochemical and biophysical research communications 21 36764210
2020 LncRNA CTBP1-AS2 is upregulated in osteoarthritis and increases the methylation of miR-130a gene to inhibit chondrocyte proliferation. Clinical rheumatology 21 32388751
2020 CTBP1‑AS2 inhibits proliferation and induces autophagy in ox‑LDL‑stimulated vascular smooth muscle cells by regulating miR‑195‑5p/ATG14. International journal of molecular medicine 21 32626936
2019 The CtBP1-HDAC1/2-IRF1 transcriptional complex represses the expression of the long noncoding RNA GAS5 in human osteosarcoma cells. International journal of biological sciences 21 31337976
2019 CTBP1 Confers Protection for Hippocampal and Cortical Neurons in Rat Models of Alzheimer's Disease. Neuroimmunomodulation 21 31340205
2020 Long non-coding RNA CTBP1-AS2 enhances cervical cancer progression via up-regulation of ZNF217 through sponging miR-3163. Cancer cell international 19 32742190
2020 The Effect of Protein Source on the Physicochemical, Nutritional Properties and Microstructure of High-Protein Bars Intended for Physically Active People. Foods (Basel, Switzerland) 19 33076297
2018 CTBP1/CYP19A1/estradiol axis together with adipose tissue impacts over prostate cancer growth associated to metabolic syndrome. International journal of cancer 19 30152543
2017 Influence of package and health-related claims on perception and sensory acceptability of snack bars. Food research international (Ottawa, Ont.) 19 28941673
2016 CtBP1 associates metabolic syndrome and breast carcinogenesis targeting multiple miRNAs. Oncotarget 19 26933806
2023 MAT1A Suppression by the CTBP1/HDAC1/HDAC2 Transcriptional Complex Induces Immune Escape and Reduces Ferroptosis in Hepatocellular Carcinoma. Laboratory investigation; a journal of technical methods and pathology 18 37230466
2021 ETV5-mediated upregulation of lncRNA CTBP1-DT as a ceRNA facilitates HGSOC progression by regulating miR-188-5p/MAP3K3 axis. Cell death & disease 18 34887384
2020 CtBP1-Mediated Membrane Fission Contributes to Effective Recycling of Synaptic Vesicles. Cell reports 18 32075774
2018 Engineering therapeutic T cells to suppress alloimmune responses using TCRs, CARs, or BARs. American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons 18 29603617
2020 lncRNA CTBP1-AS2 promotes proliferation and migration of glioma by modulating miR-370-3p-Wnt7a-mediated epithelial-mesenchymal transition. Biochemistry and cell biology = Biochimie et biologie cellulaire 17 33150795
2019 CTBP1 depletion on prostate tumors deregulates miRNA/mRNA expression and impairs cancer progression in metabolic syndrome mice. Cell death & disease 17 30931931
2019 A pathogenic CtBP1 missense mutation causes altered cofactor binding and transcriptional activity. Neurogenetics 17 31041561
2006 Expression of avian C-terminal binding proteins (Ctbp1 and Ctbp2) during embryonic development. Developmental dynamics : an official publication of the American Association of Anatomists 17 16258936
2021 Of bars and stripes: A Malawi cichlid hybrid cross provides insights into genetic modularity and evolution of modifier loci underlying colour pattern diversification. Molecular ecology 16 34322938
2021 CircIMMP2L promotes esophageal squamous cell carcinoma malignant progression via CtBP1 nuclear retention dependent epigenetic modification. Clinical and translational medicine 16 34586741
2009 CtBP1/BARS Gly172-->Glu mutant structure: impairing NAD(H)-binding and dimerization. Biochemical and biophysical research communications 16 19351597
2005 Purification and functional properties of the membrane fissioning protein CtBP3/BARS. Methods in enzymology 16 16413278
2020 LncRNA CTBP1-AS2 sponges miR-216a to upregulate PTEN and suppress endometrial cancer cell invasion and migration. Journal of ovarian research 15 32293505
2020 LncRNA CTBP1-AS2 regulates miR-216a/ PTEN to suppress ovarian cancer cell proliferation. Journal of ovarian research 15 32711584
2012 CtBP1 interacts with Ikaros and modulates pituitary tumor cell survival and response to hypoxia. Molecular endocrinology (Baltimore, Md.) 15 22301782
2020 The PRDM14-CtBP1/2-PRC2 complex regulates transcriptional repression during the transition from primed to naïve pluripotency. Journal of cell science 14 32661086
2022 CTBP1 and CTBP2 mutations underpinning neurological disorders: a systematic review. Neurogenetics 13 36331689
2021 CtBP1/2 differentially regulate genomic stability and DNA repair pathway in high-grade serous ovarian cancer cell. Oncogenesis 13 34253710
2017 Benzotriazole Enhances Cell Invasive Potency in Endometrial Carcinoma Through CTBP1-Mediated Epithelial-Mesenchymal Transition. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 13 29262396
2016 Silencing of CtBP1 suppresses the migration in human glioma cells. Journal of molecular histology 13 27160109
2022 Development of energy-rich protein bars and in vitro determination of angiotensin I-converting enzyme inhibitory antihypertensive activities. Food science & nutrition 12 35432955
2020 LncRNA CTBP1-AS2 Promotes Cell Proliferation in Hepatocellular Carcinoma by Regulating the miR-623/Cyclin D1 Axis. Cancer biotherapy & radiopharmaceuticals 12 32522013
2020 LncRNA CTBP1-AS2 Facilitates Gastric Cancer Progression via Regulating the miR-139-3p/MMP11 Axis. OncoTargets and therapy 12 33204108
2016 Instrumental and Sensory Texture Attributes of High-Protein Nutrition Bars Formulated with Extruded Milk Protein Concentrate. Journal of food science 12 27037608
2012 Development, characterization, and optimization of protein level in date bars using response surface methodology. TheScientificWorldJournal 12 22792044
2021 CTBP1 strengthens the cisplatin resistance of gastric cancer cells by upregulating RAD51 expression. Oncology letters 11 34630717
2019 miR-539-3P inhibits proliferation and invasion of gastric cancer cells by targeting CTBP1. International journal of clinical and experimental pathology 11 31933979
2018 EVI1 carboxy-terminal phosphorylation is ATM-mediated and sustains transcriptional modulation and self-renewal via enhanced CtBP1 association. Nucleic acids research 11 29939287
2010 Inhibition of CtBP1 activity by Akt-mediated phosphorylation. Journal of molecular biology 11 20361981
1995 Cereal and nut bars, nutritional quality and storage stability. Plant foods for human nutrition (Dordrecht, Netherlands) 11 8577648

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