Affinage

NACC1

Nucleus accumbens-associated protein 1 · UniProt Q96RE7

Length
527 aa
Mass
57.3 kDa
Annotated
2026-04-29
100 papers in source corpus 39 papers cited in narrative 38 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

NACC1 is a BTB/POZ-domain transcriptional co-repressor that homodimerizes to form dynamic nuclear bodies and recruits chromatin-modifying complexes—including HDAC3/4 and CoREST—to repress target genes such as Gadd45GIP1, FOXQ1, and ZEB1, while also heterodimerizing with other BTB/POZ proteins (BCL6, Miz1, ZID, ZF5) to modulate their transcriptional activities (PMID:10934270, PMID:16033423, PMID:17254023, PMID:25484205). In neurons, NACC1 mediates activity-dependent recruitment of the proteasome to dendritic spines through PKC-dependent phosphorylation at S245 that governs its nuclear–cytoplasmic shuttling, and interacts with synaptic proteins SynGAP1 and GluK2A to support glutamatergic neurotransmission; a recurrent de novo R298W mutation causes a neurodevelopmental syndrome with epilepsy by disrupting these synaptic interactions and pathologically increasing SUMOylation (PMID:17699672, PMID:16045493, PMID:37533751, PMID:38388424). In the immune system, NACC1 destabilizes FoxP3 in regulatory T cells, restrains CD4+ and CD8+ T-cell memory formation via ROCK1/autophagy signaling, and bridges MAVS to TBK1 to potentiate type I interferon responses during viral infection (PMID:35767626, PMID:37465969, PMID:31235549). In cancer cells, cytoplasmic NACC1 assembles a Cul3-based E3 ubiquitin ligase that degrades Cyclin B1 to promote mitotic exit and taxane resistance, and its multi-site SUMOylation stabilizes nuclear bodies required for proliferation (PMID:37019189, PMID:36527749).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1997 High

    Identifying NACC1 as a cocaine-regulated POZ/BTB-domain gene in the nucleus accumbens established its neural expression and domain architecture, opening the question of its molecular function.

    Evidence cDNA cloning with in situ hybridization and Northern blot in rat brain after cocaine self-administration

    PMID:9278521

    Open questions at the time
    • No function assigned beyond expression pattern
    • POZ domain role uncharacterized
  2. 2000 High

    Demonstrating that NAC1 represses transcription via its POZ domain and that overexpression blocks cocaine sensitization established it as a nuclear transcriptional repressor with behavioral relevance.

    Evidence Gal4-luciferase reporter assay, mammalian two-hybrid, adenoviral overexpression in rat nucleus accumbens

    PMID:10934270

    Open questions at the time
    • Corepressor recruitment mechanism unknown
    • Direct DNA-binding capacity unresolved
  3. 2005 High

    Identification of HDAC3/4 and CoREST as direct NAC1 partners, and PKC-S245 phosphorylation as a switch for nuclear-cytoplasmic distribution, defined the enzymatic basis of NAC1-mediated repression and its activity-dependent regulation in neurons.

    Evidence Co-IP, GST pulldown, HDAC inhibitor rescue of reporter repression; PKC-site mutagenesis with immunofluorescence in primary neurons

    PMID:16033423 PMID:16045493 PMID:17254023

    Open questions at the time
    • Direct genomic targets of NAC1 repression not yet mapped
    • Whether HDAC3 vs. HDAC4 recruitment is context-specific
  4. 2007 High

    Discovery that NAC1 recruits the proteasome to dendritic spines in an activity-dependent manner, and that it represses Gadd45GIP1 to sustain cancer cell growth, revealed dual cytoplasmic and nuclear effector functions.

    Evidence Co-IP of NAC1 with proteasome subunits, Nac1 KO neurons lacking spine proteasome recruitment; SAGE-based target identification with siRNA/ectopic expression in cancer cells

    PMID:17699672 PMID:17804717

    Open questions at the time
    • Mechanism of proteasome cargo recognition by NAC1 unclear
    • Whether Gadd45GIP1 is a direct transcriptional target not resolved by ChIP
  5. 2009 High

    Crystal structure of the NAC1 POZ domain at 2.1 Å confirmed dimeric architecture, while functional studies showed homodimerization is essential for paclitaxel resistance via the Gadd45 pathway and that NAC1 interacts with Nanog to regulate ES cell proliferation.

    Evidence X-ray crystallography; dominant-negative disruption of homodimerization with chemosensitivity assays; Nanog-NAC1 co-IP with ERas/PI3K pathway readouts

    PMID:19305429 PMID:19366700 PMID:19407373

    Open questions at the time
    • How NAC1 transitions between transcription factor and ES cell pluripotency roles
    • No co-crystal with DNA or HDAC partners
  6. 2012 High

    Identification of NAC1 as an actin monomer-binding protein required for cytokinesis, and mapping of its bipartite NLS, revealed a structural role in cell division beyond transcriptional repression.

    Evidence Direct actin-binding assay, multinucleation phenotype upon NAC1 loss, rescue in Nac1-null fibroblasts; NLS mutagenesis with importin pathway inhibition

    PMID:22665369 PMID:22761335

    Open questions at the time
    • Whether actin binding and transcriptional repression are separable functions in vivo
    • Structural basis of actin-BTB domain interaction unknown
  7. 2014 High

    Crystal structures of NAC1-Miz1 and BCL6-Miz1 POZ heterodimers defined the structural basis for NAC1 heterodimerization and showed that NAC1 sequesters Miz1 into nuclear bodies to relieve p21 repression.

    Evidence X-ray crystallography of heterodimeric POZ complexes, co-IP, siRNA knockdown of NAC1 increasing p21

    PMID:24702277 PMID:25484205

    Open questions at the time
    • Full repertoire of POZ heterodimer partners in vivo not defined
    • Genome-wide transcriptional consequences of Miz1 sequestration unknown
  8. 2019 High

    NAC1 was shown to bridge MAVS and TBK1 via distinct domains to potentiate type I IFN signaling, establishing an innate immune function; separately, critical dimerization residues (Met7, Leu90) were mapped and targeted by the small molecule NIC3.

    Evidence Domain-mapping co-IP with viral infection; HTS identifying NIC3, mutagenesis of Leu90, xenograft chemosensitization

    PMID:31101655 PMID:31235549

    Open questions at the time
    • Whether NAC1's antiviral role operates in vivo during natural infection
    • Pharmacokinetics and selectivity of NIC3 in vivo
  9. 2022 High

    Genetic studies in Nacc1−/− mice revealed NAC1 as a negative regulator of FoxP3 stability in Tregs and of LDHA-driven lactic acid production in tumors, linking NAC1 to adaptive immune regulation and tumor immune evasion.

    Evidence Knockout mouse with FoxP3 acetylation/stability assays; CRISPR KO with adoptive T-cell transfer in immunocompetent mice

    PMID:35767626 PMID:36150745

    Open questions at the time
    • Direct mechanism by which NAC1 promotes FoxP3 deacetylation not identified
    • Whether LDHA is a direct transcriptional target confirmed by ChIP
  10. 2022 Medium

    Systematic SUMO-site mutagenesis showed that multi-site SUMOylation facilitates NAC1 nuclear body formation and is required for its pro-proliferative activity, adding a post-translational layer to nuclear body regulation.

    Evidence Mutagenesis of five SUMO sites, SUMOylation assay, nuclear body imaging, tumor growth assay

    PMID:36527749

    Open questions at the time
    • Identity of SUMO E3 ligases acting on NAC1 in cancer cells not defined
    • Whether SUMOylation modulates specific transcriptional targets
  11. 2023 High

    Mapping of an N-terminal NES and demonstration that cytoplasmic NAC1 forms a Cul3 E3 ligase targeting Cyclin B1 for degradation explained how NAC1 promotes mitotic exit and taxane resistance, unifying its nuclear export and ubiquitin ligase activities.

    Evidence NES mapping, ubiquitination assay, Cyclin B1 degradation kinetics, NES-blocking peptide in xenograft

    PMID:37019189

    Open questions at the time
    • Whether Cyclin B1 is the sole Cul3-NAC1 substrate
    • How NES-mediated export is triggered specifically by taxanes
  12. 2023 High

    The recurrent R298W mutation was shown to impair glutamatergic neurotransmission cell-autonomously by reducing SynGAP1/GluK2A binding and increasing pathological SUMOylation, providing a molecular mechanism for the associated neurodevelopmental syndrome.

    Evidence Autaptic neuron electrophysiology, co-IP of mutant vs. wild-type interactomes, SUMOylation assays with rescue

    PMID:37533751

    Open questions at the time
    • Whether SUMOylation-ablated R298W fully rescues synaptic function in vivo
    • Which SUMO E3 ligase(s) preferentially modify the mutant
  13. 2024 High

    A Nacc1-R284W knock-in mouse recapitulated epilepsy with altered synaptic gene networks, validating the mutation as causal for the human neurodevelopmental phenotype and revealing compensatory transcriptional changes.

    Evidence Knock-in mouse with EEG, behavioral seizure scoring, RNA-seq, immunohistochemistry

    PMID:38388424

    Open questions at the time
    • Whether seizures arise from excitatory neuron, interneuron, or circuit-level dysfunction
    • Therapeutic targets within the dysregulated synaptic gene network not identified

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the genome-wide direct target repertoire of NAC1 (by ChIP-seq), the structural basis of NAC1's interactions with non-POZ partners (HDAC3/4, proteasome, SynGAP1), how SUMOylation versus phosphorylation coordinately regulate NAC1 function in different cell types, and the full substrate spectrum of the Cul3-NAC1 E3 ligase.
  • No genome-wide ChIP-seq for direct NAC1 binding sites published
  • No structure of NAC1 in complex with HDAC, proteasome, or synaptic partners
  • Interplay between SUMOylation and S245 phosphorylation not studied

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 6 GO:0060090 molecular adaptor activity 2 GO:0008092 cytoskeletal protein binding 1 GO:0140096 catalytic activity, acting on a protein 1
Localization
GO:0005634 nucleus 5 GO:0005829 cytosol 2 GO:0005654 nucleoplasm 1
Pathway
R-HSA-74160 Gene expression (Transcription) 6 R-HSA-168256 Immune System 5 R-HSA-1640170 Cell Cycle 3 R-HSA-392499 Metabolism of proteins 2 R-HSA-5357801 Programmed Cell Death 2 R-HSA-9612973 Autophagy 2
Partners
BCL6CUL3HDAC3HDAC4MAVSRCOR1TBK1ZBTB17
Complex memberships
CoREST complexCul3 E3 ubiquitin ligase complex

Evidence

Reading pass · 38 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1997 NAC1 (NACC1) was identified as a novel transcript in rat nucleus accumbens encoding a protein with a POZ/BTB domain in its first 120 amino acids, and its mRNA levels were increased ~50% in nucleus accumbens 3 weeks after cocaine self-administration, establishing it as a cocaine-regulated gene in the brain. In situ transcription-PCR, in situ hybridization, Northern blot, cDNA cloning The Journal of neuroscience High 9278521
2000 NAC1 acts as a transcriptional repressor localized to the nucleus of neurons; it represses reporter gene transcription and interacts with other POZ/BTB proteins via its POZ/BTB domain in mammalian two-hybrid studies; adenoviral overexpression of NAC1 in rat nucleus accumbens prevented development (but not expression) of cocaine-induced behavioral sensitization. Nuclear localization imaging, Gal4-luciferase reporter assay, mammalian two-hybrid, adenoviral overexpression in vivo The Journal of neuroscience High 10934270
2002 Two NAC1 isoforms (sNAC1 and lNAC1, differing by 27 amino acids) both repress transcription in HEK293T cells, but the shorter isoform represses less effectively; both show subnuclear punctate localization; cocaine transiently increases sNAC1 levels in the nucleus accumbens 2 h after acute injection. cDNA cloning, Western blot, Gal4-luciferase reporter assay, immunofluorescence, semi-quantitative RT-PCR Neuroscience Medium 11906783
2003 The mouse Nac1 gene contains a functional AP1 binding site in an intron 1 enhancer; co-transfection with c-jun/c-fos activated the wild-type enhancer, and mutation of the AP1 site abrogated activation, establishing AP1 as a transcriptional regulator of Nac1. Promoter-reporter (luciferase), site-directed mutagenesis, co-transfection Neuroscience Medium 14521994
2005 NAC1 interacts with HDAC3 and HDAC4 via both its POZ domain and non-POZ regions; HDAC inhibition reverses NAC1-mediated transcriptional repression in neuronal-like cultures; NAC1 does not interact with NCoR, SMRT, or mSin3a, indicating selectivity for HDAC3/4 as corepressors. Co-immunoprecipitation, GST pulldown, mammalian two-hybrid, Gal4-luciferase reporter assay Journal of neurochemistry High 16033423
2005 NAC1 subcellular localization is activity-dependent: phosphorylation of residue S245 by PKC is necessary for diffuse cytoplasmic localization outside the nucleus in differentiated neurons; tetrodotoxin blocks and high-K+ depolarization induces this diffuse distribution. PKC inhibitors/activators, systematic PKC-site mutagenesis, immunofluorescence in primary cortical neurons and differentiated PC12/Neuro2A cells The European journal of neuroscience High 16045493
2006 NAC1 forms discrete nuclear bodies via homodimerization through the BTB/POZ domain; expression of a BTB/POZ-only dominant-negative disrupts these nuclear bodies, prevents tumor formation, and promotes apoptosis in cancer xenografts. Co-immunoprecipitation, double immunofluorescence, mouse xenograft model with dominant-negative expression Proceedings of the National Academy of Sciences of the United States of America High 17130457
2007 NAC1 negatively regulates transcription of Gadd45GIP1; NAC1 knockdown in SKOV3 and HeLa cells induces Gadd45GIP1 expression, while engineered NAC1 expression suppresses it; Gadd45GIP1 induction partially mediates NAC1 knockdown-induced growth arrest. SAGE, siRNA knockdown, ectopic NAC1 expression, luciferase reporter, in vitro and in vivo growth assays Cancer research High 17804717
2007 NAC1 complexes with proteins in the ubiquitin-proteasome system (cullins, Mov34) and co-translocates with the proteasome from the nucleus into dendritic spines in cortical neurons in response to proteasome inhibition or disinhibiting synaptic activity (bicuculline); NAC1-deficient neurons fail to recruit the proteasome into dendritic spines and postsynaptic density. Co-immunoprecipitation, immunofluorescence, subcellular fractionation, Nac1 knockout neurons, dominant-negative NAC1 lacking proteasome-binding domain The Journal of neuroscience High 17699672
2007 NAC1 interacts with CoREST via its POZ/BTB domain; this interaction is detected by co-immunoprecipitation in neuro-2A, HEK293T cells, and rat brain lysates; POZ/BTB homodimerization is not required for NAC1-CoREST interaction; siRNA-mediated NAC1 knockdown reverses CoREST-mediated transcriptional repression. Co-immunoprecipitation, GST pulldown, siRNA knockdown, luciferase reporter assay, endogenous brain protein interaction Journal of neurochemistry High 17254023
2008 NAC1 functions as a corepressor for multiple other POZ/BTB proteins (ZID, BCL6, ZF5, MAYVEN, NRP/B, BCoR) via its POZ/BTB domain; NAC1 does not interact with PLZF; endogenous NAC1 and BCL6 are physically associated in CNS regions. Mammalian two-hybrid, GST pulldown, co-immunoprecipitation from brain lysates, Gal4-reporter assay Neurochemistry international Medium 19121354
2009 NAC1 homodimerization contributes to paclitaxel resistance in ovarian cancer by negatively regulating the Gadd45 pathway; disruption of NAC1 homodimerization by dominant-negative BTB/POZ domain or siRNA knockdown induces Gadd45γ, which interacts with Gadd45gip1 to increase paclitaxel sensitivity. siRNA knockdown, dominant-negative expression, ectopic expression, cell viability assays, ex vivo tissue correlation Oncogene High 19305429
2009 The C-terminal pentapeptide WNAAP of Nanog's tryptophan repeat domain is sufficient for binding Nac1; Nanog and Nac1 synergistically upregulate ERas expression and promote ES cell proliferation via the PI3K/Akt pathway, while the Nanog-Nac1 interaction regulates cell cycle but not pluripotency. Gal4-DBD fusion co-immunoprecipitation, cell cycle analysis, Akt phosphorylation assay, luciferase reporter The Journal of biological chemistry Medium 19366700
2009 Crystal structure of the human Nac1 POZ domain at 2.1 Å resolution shows it crystallizes as a dimer with interaction interfaces resembling POZ-zinc finger transcription factors; the C-terminal alpha-helix is shorter than most other POZ domains. X-ray crystallography Acta crystallographica Section F High 19407373
2011 NAC1 autophagy regulation is mediated by HMGB1: NAC1 increases HMGB1 expression, cytosolic translocation, and release; the resulting cytoplasmic HMGB1 activates autophagy; NAC1 knockdown or dominant-negative expression suppresses cisplatin-induced autophagy and increases cytotoxicity. siRNA knockdown, dominant-negative expression, Western blot, HMGB1 translocation imaging, autophagy inhibitors (3-MA, chloroquine), Beclin1/Atg5 siRNA Oncogene High 21743489
2011 NAC1 nuclear bodies undergo cell cycle-dependent dynamics: they increase in number and decrease in size in S phase, disappear during mitosis, and reappear after mitosis; FRAP shows rapid exchange of NAC1 between nucleoplasm and nuclear bodies in interphase. Fluorescence recovery after photobleaching (FRAP), live-cell imaging, cell cycle synchronization Physical biology Medium 21301057
2012 NAC1 functions as an actin monomer-binding protein via its BTB domain; disruption of NAC1 by dominant-negative or siRNA reduces cell retraction and abscission during cytokinesis, causing multinucleation; NAC1 modulates the binding of actin to profilin-1, and the NAC1/actin/profilin-1 complex is crucial for cancer cell cytokinesis. Actin-binding assay, siRNA knockdown, dominant-negative expression, rescue in Nac1-deficient murine fibroblasts, multinucleation phenotype quantification Cancer research High 22761335
2012 NAC1 nuclear localization requires a bipartite NLS in the N-terminal half of the protein that functions through the importin α/β pathway; dimer formation is not required for nuclear localization; the NLS is essential for NAC1's transcriptional regulatory function. Point mutagenesis, deletion mutant analysis, GFP-fusion nuclear import assay, Bimax1 peptide inhibitor of importin α/β pathway, importin binding assay Carcinogenesis High 22665369
2013 Loss of NAC1 in Nacc1−/− mice causes vertebral patterning defects (L6 sacralization), reduced chondrocyte migratory potential, and decreased expression of matrilin-3 and matrilin-4, indicating NAC1 participates in chondrocyte motility and differentiation. Knockout mouse model, skeletal phenotyping, chondrocyte migration assay, immunostaining, gene expression analysis PloS one Medium 23922682
2013 NAC1 regulates FOXQ1 expression: NAC1 knockdown decreases FOXQ1 promoter activity and transcript; ectopic NAC1 induces FOXQ1; constitutive FOXQ1 expression rescues cell motility after NAC1 silencing, placing FOXQ1 downstream of NAC1 in cell movement regulation. siRNA knockdown, ectopic expression, luciferase reporter (promoter activity), rescue experiment, transcriptome profiling The American journal of pathology High 24200849
2014 Crystal structures of heterodimeric POZ domains of Miz1/BCL6 and Miz1/NAC1 reveal the structural basis of POZ-domain heterodimer formation; Nac1 was identified as an interactor of Miz1 via POZ domain heterodimeric interaction, and Nac1 relocalizes Miz1 to NAC1 nuclear bodies; Nac1 siRNA knockdown increases p21Cip1 levels, consistent with relief of Miz1 inhibition. Chemical crosslinking, X-ray crystallography, co-immunoprecipitation, immunofluorescence, siRNA knockdown Acta crystallographica Section F / Bioscience reports High 24702277 25484205
2016 Nac1 coordinates ES cell differentiation by activating Oct4 and inhibiting both Sox2 and Tcf3; Nac1, Oct4, Tcf3, and Sox2 form a sub-network governing mesendodermal vs. neuroectodermal fate choice. Integrative gene expression analysis, quantitative constraints modeling, gain/loss of function in mESCs Cell reports Medium 26832399
2017 NAC1 promotes somatic cell reprogramming by facilitating NANOG binding to the E-cadherin promoter and by transcriptionally repressing ZEB1 (directly) and post-transcriptionally activating miR-200 miRNAs (indirectly) to upregulate E-cadherin expression. siRNA/shRNA knockdown, ChIP, promoter-reporter assay, miR-200 expression analysis, iPSC generation efficiency Stem cell reports High 28781078
2017 NAC1 overexpression drives drug resistance in colorectal cancer cells via induction of HOXA9 expression; knockdown of HOXA9 abrogates NAC1-induced resistance, establishing a NAC1→HOXA9 axis in chemoresistance. siRNA knockdown, ectopic overexpression, cell viability assay, caspase-3/7 activity Molecular medicine reports Medium 28713930
2017 NAC1 mediates suppression of mitochondrial function in hypoxia through HIF-1α-induced expression of PDK3; NAC1-PDK3 axis inactivates pyruvate dehydrogenase and attenuates mitochondrial respiration, protecting cancer cells from apoptosis; re-expression of PDK3 in NAC1-absent cells rescues glycolysis. siRNA knockdown, ectopic expression, metabolic assays (glycolysis, oxygen consumption), xenograft model, qRT-PCR Frontiers in pharmacology Medium 29163184
2018 NAC1 forms a protein complex with CARM1 (identified by LC-MS/MS) in ovarian cancer cells; the NAC1 complex has an apparent molecular mass of 300-500 kDa (much larger than the 58 kDa monomer), indicating higher-order complex formation. FPLC size-exclusion chromatography, LC-MS/MS, co-immunoprecipitation, tissue microarray Oncotarget Medium 29983869
2019 NAC1 bridges MAVS and TBK1 in the RLR antiviral signaling pathway: NAC1's BTB/POZ domain (aa 1-133) interacts with MAVS while the remaining portion binds TBK1; NAC1 promotes TBK1 recruitment to MAVS, enhancing TBK1 and IRF3 activation and IFN-β induction upon viral infection. Co-immunoprecipitation (overexpression and virus-induced), domain mapping, siRNA knockdown, overexpression with reporter assay, antiviral assay Journal of immunology High 31235549
2019 Met7 and Leu90 in NAC1's N-terminal domain (aa 1-130) are critical for homodimerization and stability; small molecule NIC3 selectively binds Leu-90, prevents homodimerization, and leads to proteasomal NAC1 degradation, sensitizing drug-resistant tumor cells to chemotherapy. Computational analysis, high-throughput screening, in vitro binding assay, site-directed mutagenesis, cell viability assay, xenograft model The Journal of biological chemistry High 31101655
2019 NAC1 interacts with Parkin and co-localizes with it in neurons; NAC1 overexpression promotes ubiquitin-dependent proteasomal degradation of Parkin, decreases proteasomal activity, and increases cellular susceptibility to proteasome inhibition-induced toxicity; POZ/BTB domain mutation Q23L disrupts NAC1-Parkin interaction. Co-immunoprecipitation, co-localization imaging, proteasome activity assay, mutagenesis, cell viability assay Neuroscience Medium 24231739
2020 NAC1 interacts with BCL6 via its C-terminal BEN domain; the NAC1-BCL6 complex binds the FOXQ1 promoter and activates FOXQ1 transcription; NAC1 also attenuates BCL6 negative autoregulation in ovarian cancer cells. Cistrome database analysis, ChIP, co-immunoprecipitation, luciferase reporter assay, microarray analysis Aging Medium 32412910
2022 NAC1 is a negative regulator of FoxP3 in regulatory T cells (Tregs); NAC1−/− mice show increased CD4+ Tregs with higher FoxP3 acetylation and expression, slower FoxP3 turnover, and enhanced immune-suppressive activity; proinflammatory cytokines (IL-1β, TNF-α) induce NAC1 and decrease FoxP3. Knockout mouse model, flow cytometry, Treg functional assays, FoxP3 acetylation/stability measurements Science advances High 35767626
2022 Tumorous expression of NAC1 positively regulates LDHA expression at the transcriptional level, increasing lactic acid accumulation in the tumor microenvironment, which inhibits cytokine production and induces exhaustion/apoptosis of CD8+ CTLs; NAC1-depleted tumors show elevated CTL infiltration. CRISPR/Cas9 NAC1 knockout, glycolysis analysis, retroviral transduction, flow cytometry, adoptive cell transfer in immunocompetent mice Journal for immunotherapy of cancer High 36150745
2022 NAC1 is a multi-SUMO-site acceptor; SUMOylation at K167, K318, K368, K483, and K498 does not alter NAC1 localization but facilitates NAC1 nuclear body formation; SUMO-site mutant NAC1 suppresses cell proliferation and tumor growth compared to wild-type NAC1. SUMO site mutagenesis, SUMOylation assay, immunofluorescence, cell proliferation assay, animal tumor model Biochemical and biophysical research communications Medium 36527749
2023 NAC1 nuclear export is mediated by a nuclear export signal (NES) at aa 17-28; docetaxel treatment triggers nuclear-cytoplasmic shuttling of NAC1; cytoplasmic NAC1 binds cullin3 (Cul3) via its BTB domain and Cyclin B1 via its BOZ domain, forming an E3 ubiquitin ligase complex that ubiquitinates and degrades Cyclin B1, facilitating mitotic exit and docetaxel resistance. NES mapping, domain-specific binding assays, ubiquitination assay, Cyclin B1 degradation assay, NES-blocking peptide in vitro and in vivo Biochemical pharmacology High 37019189
2023 NAC1 (Nacc1) R284W (human R298W) mutant impairs glutamatergic neurotransmission in a cell-autonomous, dominant-negative manner in autaptic mouse neurons; the mutant shows reduced binding to SynGAP1 and GluK2A, and greatly increased SUMOylation; ablating SUMOylation of Nacc1-R284W partially restores SynGAP1 binding. SynGAP1, GluK2A, and several SUMO E3 ligases were identified as novel Nacc1 interaction partners in the brain. Electrophysiology (autaptic neuron recordings), co-immunoprecipitation, SUMOylation assay, brain interactome screen Frontiers in molecular neuroscience High 37533751
2024 In the Nacc1-R284W knock-in mouse model, the mutation causes epileptiform discharges, behavioral seizures, and altered synaptic gene expression (upregulation of postsynapse and ion channel genes); NACC1 nuclear immunoreactivity increases in cortical pyramidal neurons and parvalbumin interneurons, and levels of synaptic proteins are changed. Knock-in mouse model, EEG, behavioral testing, RNA-seq, immunohistochemistry, synaptic protein analysis The Journal of neuroscience High 38388424
2023 NAC1 restrains CD4+ T-cell memory formation through the ROCK1-mediated autophagy pathway; NAC1-deficient CD4+ T cells have reduced ROCK1 expression, impaired BECLIN1 phosphorylation/stabilization, and defective autophagy; forced ROCK1 expression in NAC1−/− CD4+ T cells restores autophagy and abrogates enhanced memory formation. Knockout mouse model, adoptive transfer, viral infection model, ROCK1 overexpression rescue, AMPK-mTOR pathway analysis, autophagy flux assay Journal of medical virology Medium 37465969
2025 Treg-specific NAC1 deficiency upregulates FoxP3 expression and CD36-mediated lipid metabolism in Tregs, enhancing their metabolic fitness and immunosuppressive function in acidic tumor microenvironments; NAC1-deficient Tregs show enhanced tumoral infiltration and support tumor growth. Conditional Treg-specific NAC1 deletion, xenograft mouse models, adoptive Treg transfer, metabolic assays (lipid uptake, mitochondrial function) JCI insight Medium 39773913

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2005 MicroRNA directs mRNA cleavage of the transcription factor NAC1 to downregulate auxin signals for arabidopsis lateral root development. The Plant cell 663 15829603
2000 Arabidopsis NAC1 transduces auxin signal downstream of TIR1 to promote lateral root development. Genes & development 639 11114891
2002 SINAT5 promotes ubiquitin-related degradation of NAC1 to attenuate auxin signals. Nature 369 12226665
2006 A BTB/POZ protein, NAC-1, is related to tumor recurrence and is essential for tumor growth and survival. Proceedings of the National Academy of Sciences of the United States of America 118 17130457
2011 NAC1 modulates sensitivity of ovarian cancer cells to cisplatin by altering the HMGB1-mediated autophagic response. Oncogene 108 21743489
2014 A STRESS-RESPONSIVE NAC1-regulated protein phosphatase gene rice protein phosphatase18 modulates drought and oxidative stress tolerance through abscisic acid-independent reactive oxygen species scavenging in rice. Plant physiology 103 25318938
2011 A structural view of the conserved domain of rice stress-responsive NAC1. Protein & cell 78 21337010
2009 NAC-1, a potential stem cell pluripotency factor, contributes to paclitaxel resistance in ovarian cancer through inactivating Gadd45 pathway. Oncogene 72 19305429
1997 NAC-1, a rat brain mRNA, is increased in the nucleus accumbens three weeks after chronic cocaine self-administration. The Journal of neuroscience : the official journal of the Society for Neuroscience 72 9278521
2018 LncRNA LINC00319 accelerates ovarian cancer progression through miR-423-5p/NACC1 pathway. Biochemical and biophysical research communications 69 30442370
2013 Grapevine NAC1 transcription factor as a convergent node in developmental processes, abiotic stresses, and necrotrophic/biotrophic pathogen tolerance. Journal of experimental botany 68 24043850
2007 NAC-1 controls cell growth and survival by repressing transcription of Gadd45GIP1, a candidate tumor suppressor. Cancer research 64 17804717
2000 NAC-1 is a brain POZ/BTB protein that can prevent cocaine-induced sensitization in the rat. The Journal of neuroscience : the official journal of the Society for Neuroscience 64 10934270
2010 Expression of Fatty Acid Synthase Depends on NAC1 and Is Associated with Recurrent Ovarian Serous Carcinomas. Journal of oncology 59 20508725
2021 FUS-induced circRHOBTB3 facilitates cell proliferation via miR-600/NACC1 mediated autophagy response in pancreatic ductal adenocarcinoma. Journal of experimental & clinical cancer research : CR 57 34416910
2007 NAC1 regulates the recruitment of the proteasome complex into dendritic spines. The Journal of neuroscience : the official journal of the Society for Neuroscience 54 17699672
2011 Amplification of the ch19p13.2 NACC1 locus in ovarian high-grade serous carcinoma. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 52 21240255
2008 A BTB/POZ gene, NAC-1, a tumor recurrence-associated gene, as a potential target for Taxol resistance in ovarian cancer. Clinical cancer research : an official journal of the American Association for Cancer Research 43 18483383
2011 Transcriptional and post-transcriptional regulation of a NAC1 transcription factor in Medicago truncatula roots. The New phytologist 42 21770944
2005 The POZ/BTB protein NAC1 interacts with two different histone deacetylases in neuronal-like cultures. Journal of neurochemistry 41 16033423
2017 A Recurrent De Novo Variant in NACC1 Causes a Syndrome Characterized by Infantile Epilepsy, Cataracts, and Profound Developmental Delay. American journal of human genetics 39 28132692
2015 miR-339-5p inhibits migration and invasion in ovarian cancer cell lines by targeting NACC1 and BCL6. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 39 26553360
2012 NAC1 is an actin-binding protein that is essential for effective cytokinesis in cancer cells. Cancer research 37 22761335
2011 Biological and clinical significance of NAC1 expression in cervical carcinomas: a comparative study between squamous cell carcinomas and adenocarcinomas/adenosquamous carcinomas. Human pathology 37 21889186
2007 NAC1, a cocaine-regulated POZ/BTB protein interacts with CoREST. Journal of neurochemistry 37 17254023
1967 The formation and continuous turnover of a fraction of phosphatidic acid on stimulation of NaC1 secretion by acetylcholine in the salt gland. The Journal of general physiology 37 6034504
2014 Contribution of the drought tolerance-related stress-responsive NAC1 transcription factor to resistance of barley to Ramularia leaf spot. Molecular plant pathology 36 25040333
2023 NAC1 regulates root ground tissue maturation by coordinating with the SCR/SHR-CYCD6;1 module in Arabidopsis. Molecular plant 34 36809880
2021 A Novel NIPBL-NACC1 Gene Fusion Is Characteristic of the Cholangioblastic Variant of Intrahepatic Cholangiocarcinoma. The American journal of surgical pathology 34 33999553
2022 Cowpea NAC1/NAC2 transcription factors improve growth and tolerance to drought and heat in transgenic cowpea through combined activation of photosynthetic and antioxidant mechanisms. Journal of integrative plant biology 32 36107155
2012 Fatty acid synthase expression associated with NAC1 is a potential therapeutic target in ovarian clear cell carcinomas. British journal of cancer 32 22653145
2008 NAC1, a POZ/BTB protein that functions as a corepressor. Neurochemistry international 31 19121354
2016 Nac1 Coordinates a Sub-network of Pluripotency Factors to Regulate Embryonic Stem Cell Differentiation. Cell reports 30 26832399
1999 Interrupted expression of NAC-1 augments the behavioral responses to cocaine. Synapse (New York, N.Y.) 29 10400893
2007 Expression and clinical role of the bric-a-brac tramtrack broad complex/poxvirus and zinc protein NAC-1 in ovarian carcinoma effusions. Human pathology 27 17391728
2022 Tumorous expression of NAC1 restrains antitumor immunity through the LDHA-mediated immune evasion. Journal for immunotherapy of cancer 26 36150745
2013 Identification of the NAC1-regulated genes in ovarian cancer. The American journal of pathology 26 24200849
2010 NAC1, a potential stem cell pluripotency factor expression in normal endometrium, endometrial hyperplasia and endometrial carcinoma. International journal of oncology 25 20372782
2014 Structures of heterodimeric POZ domains of Miz1/BCL6 and Miz1/NAC1. Acta crystallographica. Section F, Structural biology communications 24 25484205
2011 Cell cycle-dependent alteration in NAC1 nuclear body dynamics and morphology. Physical biology 24 21301057
2020 Circular RNA hsa_circ_0001588 promotes the malignant progression of lung adenocarcinoma by modulating miR-524-3p/NACC1 signaling. Life sciences 23 32735888
2018 Cancer-related transcription regulator protein NAC1 forms a protein complex with CARM1 for ovarian cancer progression. Oncotarget 22 29983869
2018 NACC1, as a Target of MicroRNA-331-3p, Regulates Cell Proliferation in Urothelial Carcinoma Cells. Cancers 22 30248959
2009 Expression of a BTB/POZ protein, NAC1, is essential for the proliferation of normal cyclic endometrial glandular cells and is up-regulated by estrogen. Clinical cancer research : an official journal of the American Association for Cancer Research 22 19188150
2009 The C-terminal pentapeptide of Nanog tryptophan repeat domain interacts with Nac1 and regulates stem cell proliferation but not pluripotency. The Journal of biological chemistry 22 19366700
2023 Molecular mechanisms of SNAC1 (Stress-responsive NAC1) in conferring the abiotic stress tolerance. Plant science : an international journal of experimental plant biology 21 37813193
2017 Overexpression of NAC1 confers drug resistance via HOXA9 in colorectal carcinoma cells. Molecular medicine reports 21 28713930
2002 Differences in expression, actions and cocaine regulation of two isoforms for the brain transcriptional regulator NAC1. Neuroscience 21 11906783
2022 NAC1 modulates autoimmunity by suppressing regulatory T cell-mediated tolerance. Science advances 20 35767626
2019 Identification of a small-molecule compound that inhibits homodimerization of oncogenic NAC1 protein and sensitizes cancer cells to anticancer agents. The Journal of biological chemistry 20 31101655
2018 Targeting oncogenic transcriptional corepressor Nac1 POZ domain with conformationally constrained peptides by cyclization and stapling. Bioorganic chemistry 20 29864683
2017 Silencing of NAC1 Expression Induces Cancer Cells Oxidative Stress in Hypoxia and Potentiates the Therapeutic Activity of Elesclomol. Frontiers in pharmacology 20 29163184
2016 Function of Hevea brasiliensis NAC1 in dehydration-induced laticifer differentiation and latex biosynthesis. Planta 20 27544199
2019 CRM197 reverses paclitaxel resistance by inhibiting the NAC-1/Gadd45 pathway in paclitaxel-resistant ovarian cancer cells. Cancer medicine 19 31490008
2013 Loss of NAC1 expression is associated with defective bony patterning in the murine vertebral axis. PloS one 19 23922682
2009 Structure of the human Nac1 POZ domain. Acta crystallographica. Section F, Structural biology and crystallization communications 19 19407373
2020 MiR-218-5p Suppresses the Progression of Retinoblastoma Through Targeting NACC1 and Inhibiting the AKT/mTOR Signaling Pathway. Cancer management and research 18 32821163
2020 Systemic Delivery of NAC-1 siRNA by Neuropilin-Targeted Polymersomes Sensitizes Antiangiogenic Therapy of Metastatic Triple-Negative Breast Cancer. Biomacromolecules 18 33174734
2012 Nuclear localization signal in a cancer-related transcriptional regulator protein NAC1. Carcinogenesis 16 22665369
2011 NAC1 and HMGB1 enter a partnership for manipulating autophagy. Autophagy 16 22024751
2019 NAC1 Potentiates Cellular Antiviral Signaling by Bridging MAVS and TBK1. Journal of immunology (Baltimore, Md. : 1950) 15 31235549
2014 Nac1 interacts with the POZ-domain transcription factor, Miz1. Bioscience reports 15 24702277
2003 The mouse nac1 gene, encoding a cocaine-regulated Bric-a-brac Tramtrac Broad complex/Pox virus and Zinc finger protein, is regulated by AP1. Neuroscience 15 14521994
2022 Circ_0027089 regulates NACC1 by targeting miR-136-5p to aggravate the development of hepatitis B virus-related hepatocellular carcinoma. Anti-cancer drugs 14 34419960
2017 NAC1 Regulates Somatic Cell Reprogramming by Controlling Zeb1 and E-cadherin Expression. Stem cell reports 14 28781078
2022 NAC1 Maintains Root Meristem Activity by Repressing the Transcription of E2Fa in Arabidopsis. International journal of molecular sciences 13 36293114
2005 Activity-dependent subcellular localization of NAC1. The European journal of neuroscience 13 16045493
2022 MiR-361-3p alleviates cerebral ischemia-reperfusion injury by targeting NACC1 through the PINK1/Parkin pathway. Journal of molecular histology 12 35067807
2022 Expression of NAC1 Restrains the Memory Formation of CD8+ T Cells during Viral Infection. Viruses 12 36016335
2020 NACC-1 regulates hepatocellular carcinoma cell malignancy and is targeted by miR-760. Acta biochimica et biophysica Sinica 12 32091103
2021 Unclassified low grade spindle cell sarcoma with storiform pattern characterized by recurrent novel EWSR1/FUS-NACC1 fusions. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 11 33859361
2021 Silencing of NACC1 inhibits the proliferation, migration and invasion of nasopharyngeal carcinoma cells via regulating the AKT/mTOR signaling pathway. Oncology letters 11 34691255
2020 NAC1 attenuates BCL6 negative autoregulation and functions as a BCL6 coactivator of FOXQ1 transcription in cancer cells. Aging 11 32412910
1999 Immunoregulation of encephalitogenic MBP-NAc1-11-reactive T cells by CD4+ TCR-specific T cells involves IL-4, IL-10 and IFN-gamma. Autoimmunity 11 10789989
2024 LncRNA81246 regulates resistance against tea leaf spot by interrupting the miR164d-mediated degradation of NAC1. The Plant journal : for cell and molecular biology 10 39590921
2023 An overview of the co-transcription factor NACC1: Beyond its pro-tumor effects. Life sciences 10 38030057
2016 Protein complex formation and intranuclear dynamics of NAC1 in cancer cells. Archives of biochemistry and biophysics 10 27424155
2007 Requirement for the POZ/BTB protein NAC1 in acute but not chronic psychomotor stimulant response. Behavioural brain research 10 17945361
2023 An intellectual-disability-associated mutation of the transcriptional regulator NACC1 impairs glutamatergic neurotransmission. Frontiers in molecular neuroscience 9 37533751
2017 NAC1 promotes the migration of prostate cancer cells and participates in osteoclastogenesis by negatively regulating IFNβ. Oncology letters 9 29435019
2013 NAC1, A POZ/BTB protein interacts with Parkin and may contribute to Parkinson's disease. Neuroscience 9 24231739
2003 The relationship between cocaine-induced increases in NAC1 and behavioral sensitization. Pharmacology, biochemistry, and behavior 9 12759112
2023 Exosome-transported circHDAC1_004 Promotes Proliferation, Migration, and Angiogenesis of Hepatocellular Carcinoma by the miR-361-3p/NACC1 Axis. Journal of clinical and translational hepatology 8 37577235
2006 Expression of NAC1 up-stream regulatory region and its relationship to the lateral root initiation induced by gibberellins and auxins. Science in China. Series C, Life sciences 8 17172049
2023 Identification of a NACC1-Regulated Gene Signature Implicated in the Features of Triple-Negative Breast Cancer. Biomedicines 7 37189841
2023 NAC1 confines virus-specific memory formation of CD4+ T cells through the ROCK1-mediated pathway. Journal of medical virology 7 37465969
2003 NAC1, a POZ/BTB protein present in the adult mammalian brain, triggers apoptosis after adenovirus-mediated overexpression in PC-12 cells. Neuroscience research 7 12725910
2023 Mechanistic insights of NAC1 nuclear export and its role in ovarian cancer resistance to docetaxel. Biochemical pharmacology 6 37019189
2021 A New Case of de novo Variant c.892C>T (p.Arg298Trp) in NACC1: A First Case Report From China. Frontiers in pediatrics 6 34869110
2024 Nacc1 Mutation in Mice Models Rare Neurodevelopmental Disorder with Underlying Synaptic Dysfunction. The Journal of neuroscience : the official journal of the Society for Neuroscience 5 38388424
2024 NAC1 promotes stemness and regulates myeloid-derived cell status in triple-negative breast cancer. Molecular cancer 5 39243032
2022 A Low Grade Nasopharyngeal sarcoma With FUS::NACC1 Fusion and Immunohistochemical Evidence of Epithelial Differentiation: Expanding the Clinicopathologic Spectrum of an Emerging Entity. Head and neck pathology 5 36169794
2018 NAC1/HMGB1 Signaling Pathway Is Associated with Epithelial-mesenchymal Transition, Invasion, and Metastasis of Lung Cancer Cell Line. Annals of clinical and laboratory science 5 30373858
2016 [Expression analysis of miR164 and its target gene NAC1 in response to low nitrate availability in Betula luminifera]. Yi chuan = Hereditas 5 26907779
2019 Nac1 facilitates pluripotency gene activation for establishing somatic cell reprogramming. Biochemical and biophysical research communications 4 31412978
2012 NAC1, a BTB/POZ protein overexpressed in uterine sarcomas. Anticancer research 4 22993327
2025 Metabolic fitness of NAC1-deficient Tregs in the tumor microenvironment fuels tumor growth. JCI insight 3 39773913
2024 Hyperkinetic Movement Disorder Caused by the Recurrent c.892C>T NACC1 Variant. Movement disorders clinical practice 3 38698576
2023 Transcription factor NAC1 activates expression of peptidase-encoding AtCEPs in roots to limit root hair growth. Plant physiology 3 37801618
2022 Multi-SUMOylation of NAC1 is essential for the growth of prostate cancer cells. Biochemical and biophysical research communications 3 36527749