Affinage

KCNIP3

Calsenilin · UniProt Q9Y2W7

Length
256 aa
Mass
29.2 kDa
Annotated
2026-06-10
100 papers in source corpus 24 papers cited in narrative 24 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

KCNIP3 (DREAM/KChIP3/calsenilin) is a bifunctional neuronal calcium sensor that couples intracellular Ca2+ signals to both gene transcription and ion channel behavior (PMID:10078534, PMID:11598014). In its metal-regulated form it acts as a sequence-specific transcriptional repressor: the Ca2+-free protein assembles into a DNA-binding tetramer that engages the downstream regulatory element (DRE), and Ca2+ binding to EF-hands 3 and 4 drives dimerization and release from DNA, while constitutive Mg2+ binding at EF-2 stabilizes the monomer required for sequence-specific DRE recognition (PMID:10078534, PMID:11535596, PMID:15746104). Through this repressor activity DREAM controls a defined set of target genes including prodynorphin, BDNF, GFAP, the Na+/Ca2+ exchanger NCX3, and the NF-kB inhibitor A20, thereby shaping pain processing and central sensitization (PMID:19223600, PMID:21167062), astrogliogenesis downstream of PACAP-cAMP-Ca2+ signaling (PMID:19238593), Ca2+-regulated secretion (PMID:18393943), and inflammatory and fibrotic responses via repression of A20 (PMID:34751735, PMID:36289219). In parallel, KChIP3 functions as a cytoplasmic/membrane auxiliary subunit of Kv4-family A-type potassium channels, promoting Kv4 tetramer assembly in the ER, rescuing surface expression, and tuning gating kinetics, and it forms ternary Kv4.2-KChIP3-DPP10 complexes that set firing properties of neurons (PMID:11598014, PMID:16123112, PMID:15485870, PMID:20943905). Beyond channels, KChIP3 directly binds and regulates surface trafficking of TRPV1 and the NMDAR NR1 subunit to limit Ca2+ influx and confer neuroprotection (PMID:20519532, PMID:29335353), couples to the TSH receptor (PMID:19299442), and acts as a Ca2+-sensitive brake on mucin granule exocytosis in colonic goblet cells (PMID:30272559). Its subcellular partitioning is controlled by sumoylation at K26 and K90, which promotes nuclear accumulation (PMID:21070824), and its expression is subject to FMRP-mediated translational suppression during homeostatic plasticity (PMID:27147118). Genetic loss of KCNIP3 enhances learning and synaptic plasticity (PMID:19110430) and increases pain sensitivity and negative affect (PMID:30740043), underscoring its role as a repressive set-point regulator across neuronal and non-neuronal systems.

Mechanistic history

Synthesis pass · year-by-year structured walk · 18 steps
  1. 1999 High

    Established the founding mechanism: DREAM is a Ca2+-regulated transcriptional repressor that binds the DRE DNA element through EF-hand-dependent Ca2+ sensing, defining a direct link between calcium signaling and gene repression.

    Evidence DNA-binding assays, EF-hand mutagenesis, and transcriptional reporter assays on prodynorphin and c-fos promoters

    PMID:10078534

    Open questions at the time
    • Did not resolve the oligomeric basis of DNA binding versus Ca2+ release
    • In vivo target gene set not yet defined
  2. 2001 High

    Resolved the biophysical switch: the Ca2+-free protein is a DNA-binding tetramer that dimerizes and loses DNA binding upon Ca2+ loading, explaining how calcium toggles repressor activity.

    Evidence Equilibrium Ca2+ binding, DLS, SEC, ITC, and EMSA on full-length and C-terminal fragments

    PMID:11535596

    Open questions at the time
    • Did not address the role of other divalent cations
    • No structural model of the DNA-bound tetramer
  3. 2005 High

    Distinguished metal-specific roles, showing Mg2+ at EF-2 is constitutively bound and required for sequence-specific DNA binding while Ca2+ at EF-3/EF-4 drives dimerization, refining the dual-metal regulatory logic.

    Evidence ITC, SEC, EMSA with EF-hand point mutants, and NMR structural analysis

    PMID:15746104

    Open questions at the time
    • Molten-globule apo state not crystallographically resolved
    • Physiological Mg2+/Ca2+ competition in cells not measured
  4. 2001 High

    Defined the channel arm of KChIP3 function and its tissue restriction, linking KChIP3/Kv4 expression to A-type K+ current density and neuronal firing rates and showing a nervous-system-restricted gene with multiple isoforms.

    Evidence Single-cell RT-PCR with slice patch-clamp in dopaminergic neurons; cDNA cloning, in situ hybridization, and Northern blot for isoform/expression mapping

    PMID:11161465 PMID:11598014

    Open questions at the time
    • Causal direction between channel expression and firing only correlational in [#3]
    • Functional roles of EF-hand-lacking isoforms unresolved
  5. 2005 Medium

    Mapped how KChIP3 builds and remodels Kv4 channels, showing it drives ER tetramer assembly, rescues trafficking-deficient mutants, and forms ternary Kv4.2-KChIP3-DPP10 complexes with distinct gating.

    Evidence Co-IP from rat brain and oocytes, expression of zinc-site assembly mutants, and whole-cell electrophysiology in heterologous systems

    PMID:15485870 PMID:16123112

    Open questions at the time
    • Stoichiometry of native ternary complexes in brain not quantified
    • Structural basis of assembly chaperone activity unknown
  6. 2001 Medium

    Identified a pro-apoptotic and amyloidogenic role, connecting calsenilin/DREAM to caspase-dependent death and Abeta42 production with presenilin 2.

    Evidence Antisense knockdown, overexpression, caspase inhibitor treatment, and Abeta ELISA

    PMID:11259376

    Open questions at the time
    • Mechanism linking transcriptional/channel functions to apoptosis not defined
    • Single lab, no genetic validation
  7. 2008 Medium

    Showed in vivo that DREAM negatively regulates CREB-dependent transcription, with knockout enhancing learning, synaptic plasticity, and protection from aging.

    Evidence dream-/- knockout mice with behavioral, plasticity, and CREB-activity assays

    PMID:19110430

    Open questions at the time
    • Direct DRE targets mediating the cognitive phenotype not enumerated
    • Distinction from channel-dependent effects unresolved
  8. 2009 Medium

    Demonstrated activity-dependent nuclear redistribution and target repression, linking fear conditioning to loss of Kv4.2 membrane association, increased nuclear KChIP3, and prodynorphin repression.

    Evidence KChIP3 KO behavior, subcellular fractionation, Kv4.2 co-IP, and prodynorphin RT-PCR

    PMID:19223600

    Open questions at the time
    • Signal triggering nuclear translocation not identified
    • Whether redistribution is causal or correlative not established
  9. 2009 Medium

    Extended the transcriptional repressor role to pain and glial development, showing DREAM represses spinal prodynorphin/BDNF for central sensitization and activates GFAP via a PACAP-cAMP-Ca2+ cascade in astrogliogenesis.

    Evidence Transgenic dominant-active DREAM mice with spinal reflex and gene expression assays; GFAP promoter reporter and KO analysis

    PMID:19238593 PMID:21167062

    Open questions at the time
    • DREAM acting as activator vs repressor at GFAP not mechanistically reconciled
    • cAMP-responsiveness structural basis not mapped
  10. 2010 Medium

    Broadened the partner repertoire beyond channels, mapping direct interactions with TSHR, the NMDAR NR1 C0 domain, and a role in Ca2+-regulated secretion via NCX3 repression.

    Evidence Co-IP, pull-down domain mapping, electrophysiology, transgenic mice, and PC12 secretion/Ca2+ imaging with isoform comparison

    PMID:18393943 PMID:19299442 PMID:20519532

    Open questions at the time
    • Which interactions are direct vs complex-mediated not uniformly tested
    • Stoichiometry and competition among membrane partners unknown
  11. 2010 Medium

    Defined regulation of KChIP3 subcellular targeting through sumoylation at K26/K90 via Ubc9, controlling nuclear accumulation without altering DNA binding.

    Evidence Yeast two-hybrid, in vitro sumoylation with K-to-R mutants, and subcellular fractionation/immunofluorescence

    PMID:21070824

    Open questions at the time
    • SUMO isopeptidase counter-regulation not identified
    • Link between sumoylation and activity-dependent translocation unresolved
  12. 2010 Medium

    Clarified KChIP subunit redundancy in cortex, showing KChIP2/3/4 jointly associate with Kv4.2 and that combined loss markedly remodels A-type current beyond single KChIP3 deletion.

    Evidence Co-IP from mouse cortex with KO and multi-KChIP RNAi plus patch-clamp

    PMID:20943905

    Open questions at the time
    • Subunit-specific contributions to gating not isolated
    • Compensatory mechanisms among KChIPs not defined
  13. 2014 High

    Established a non-neuronal secretory role and a druggable Kv4 interface, showing KChIP3 is a Ca2+-sensitive brake on mucin granule exocytosis and that NS5806 binds the Ca2+-bound C-terminus to enhance Kv4.3 affinity.

    Evidence Kcnip3-/- mice and colonic cell gain/loss-of-function with granule co-localization; fluorescence/ITC binding and KChIP3 mutagenesis (Tyr-174, Phe-218)

    PMID:25228688 PMID:30272559

    Open questions at the time
    • Granule-association partner of KChIP3 not identified
    • Whether the NS5806 site is exploited physiologically unknown
  14. 2018 High

    Mapped a direct KChIP3-TRPV1 interaction and showed a derived peptide reduces TRPV1 surface expression and inflammatory thermal hyperalgesia independently of endogenous KChIP3.

    Evidence Domain-mapping co-IP/pull-down, surface biotinylation, DRG Ca2+ imaging, and TAT-31-50 peptide injection in WT and Kcnip3-/- rats

    PMID:29335353

    Open questions at the time
    • Endogenous KChIP3 regulation of TRPV1 in vivo not isolated
    • Structural basis of dual N/C-terminal TRPV1 binding unresolved
  15. 2021 High

    Defined a pro-inflammatory transcriptional axis, showing neutrophil DREAM represses A20 to enhance IKKbeta activation, SNAP-23 phosphorylation, degranulation, and vaso-occlusion in sickle cell disease.

    Evidence Intravital microscopy, DREAM KO mice, IKKbeta inhibition, phosphorylation assays, and HL-60 knockdown

    PMID:34751735

    Open questions at the time
    • Direct DRE binding at the A20 promoter in neutrophils not shown
    • Ca2+ trigger for DREAM in this context not defined
  16. 2022 High

    Generalized the DREAM-A20 axis to fibrosis, showing DREAM-null mice have elevated A20 and resist fibrosis while fibroblast A20 deletion is sufficient to drive SSc-like disease.

    Evidence DREAM-null and fibroblast-specific A20 conditional KO mice, TGF-beta stimulation, and bleomycin fibrosis models

    PMID:36289219

    Open questions at the time
    • Whether DREAM represses A20 via canonical DRE binding in fibroblasts not confirmed
    • Upstream Ca2+ regulation in fibroblasts unaddressed
  17. 2019 Medium

    Established whole-organism consequences of KCNIP3 loss, showing KO rats have enhanced pain and negative affect with transcriptomic upregulation of dopamine and neurodevelopmental genes.

    Evidence CRISPR Kcnip3-/- rats with nociceptive and affective behavior plus forebrain RNA-seq

    PMID:30740043

    Open questions at the time
    • Which transcriptomic changes are direct DREAM targets unknown
    • Circuit basis of affective phenotype undefined
  18. 2016 Medium

    Identified upstream translational control of KChIP3, showing FMRP suppresses KChIP3 translation via S6K1-dependent S499 phosphorylation during ethanol-induced homeostatic plasticity.

    Evidence In vivo chronic intermittent ethanol, immunoblot, FMRP-mRNA IP, and S6K1 inhibition in hippocampal slices

    PMID:27147118

    Open questions at the time
    • Functional consequence of reduced KChIP3 on channel/transcription not measured here
    • Direct FMRP binding site on KChIP3 mRNA not mapped

Open questions

Synthesis pass · forward-looking unresolved questions
  • How DREAM's nuclear transcriptional repressor function is mechanistically coordinated with its cytoplasmic/membrane channel- and receptor-modulating roles, and what signals dictate the partitioning, remains unresolved.
  • No integrated model linking activity-dependent translocation, sumoylation, and target-gene selection
  • Structure of the DNA-bound vs partner-bound states not determined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 8 GO:0098772 molecular function regulator activity 6 GO:0140299 molecular sensor activity 4 GO:0003677 DNA binding 3 GO:0060089 molecular transducer activity 2
Localization
GO:0005886 plasma membrane 4 GO:0005634 nucleus 3 GO:0005829 cytosol 2 GO:0005783 endoplasmic reticulum 1 GO:0031410 cytoplasmic vesicle 1
Pathway
R-HSA-74160 Gene expression (Transcription) 4 R-HSA-112316 Neuronal System 3 R-HSA-162582 Signal Transduction 3 R-HSA-168256 Immune System 2 R-HSA-5357801 Programmed Cell Death 1
Partners
DPP10FMR1GRIN1KCND2KCND3TRPV1TSHRUBE2I
Complex memberships
Kv4.2-KChIP3-DPP10 ternary channel complex

Evidence

Reading pass · 24 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 DREAM (KCNIP3/KChIP3/calsenilin) functions as a Ca2+-regulated transcriptional repressor that specifically binds to the downstream regulatory element (DRE) DNA sequence; upon Ca2+ stimulation, Ca2+ binding to its EF-hand domains prevents DRE binding and repressor function. Mutation of the EF-hands abolishes the Ca2+ response. DREAM represses transcription from the prodynorphin and c-fos promoters. DNA binding assays, EF-hand mutagenesis, transcriptional reporter assays, protein-DNA interaction Nature High 10078534
2001 Calsenilin/DREAM/KChIP3 binds 3 Ca2+ ions with Kd ~14 µM; the Ca2+-free protein forms a tetramer that binds DRE DNA (Kd ~75 nM for first site, ~640 nM for three additional sites), while the Ca2+-bound protein dimerizes and loses DNA binding. The C-terminal EF-hand-containing fragment (residues 65–256) is sufficient for Ca2+-regulated, sequence-specific DRE binding. Equilibrium Ca2+ binding measurements, dynamic light scattering, size exclusion chromatography, isothermal titration calorimetry, electrophoretic mobility shift assay (EMSA) The Journal of biological chemistry High 11535596
2005 Mg2+ and Ca2+ differentially regulate DREAM (KCNIP3): Mg2+ binds constitutively to EF-2 (Kd ~13 µM), stabilizes DREAM as a monomer, and is essential for sequence-specific DRE binding, whereas Ca2+ binds to EF-3 and EF-4, induces protein dimerization, and binding of even a single Ca2+ at EF-3 or EF-4 is sufficient to abolish DNA binding. NMR shows metal-free DREAM adopts a molten-globule-like structure. ITC, size-exclusion chromatography, EMSA with EF-hand point mutants, NMR structural analysis The Journal of biological chemistry High 15746104
2001 KChIP3/DREAM/calsenilin acts as a modulator of Kv4.3-mediated A-type potassium channels in dopaminergic substantia nigra neurons; Kv4.3L and KChIP3.1 mRNA levels are tightly correlated with A-type channel density and pacemaker frequency, indicating transcriptional control of channel gene expression tunes firing rates. Multiplex and quantitative real-time single-cell RT-PCR combined with slice patch-clamp electrophysiology The EMBO journal High 11598014
2005 KChIP3 and DPP10 simultaneously associate with Kv4.2 proteins to form ternary Kv4.2+KChIP3+DPP10 complexes in rat brain and in heterologous expression systems; the ternary complex produces ISA-like currents with very rapid recovery from inactivation (~18–26 ms) distinct from binary Kv4.2+KChIP3 or Kv4.2+DPP10 channels. Immunoprecipitation from rat brain and Xenopus oocytes, whole-cell electrophysiology in oocytes and CHO cells The Journal of physiology High 16123112
2004 KChIP3 drives Kv4 channel subunit assembly into tetramers within the endoplasmic reticulum, independently of its effects on channel trafficking; KChIP3 rescues surface expression of Kv4.2 zinc-site tetramerization mutants that are otherwise trapped in the ER, and alters gating kinetics (reduced time to peak, faster inactivation, ~3–4 fold slower recovery from inactivation). Expression of Kv4.2 zinc-binding site mutants with KChIP3 in heterologous cells; whole-cell patch-clamp electrophysiology The Journal of biological chemistry Medium 15485870
2001 Calsenilin/DREAM/KChIP3 has a pro-apoptotic function: antisense-mediated knockdown attenuates apoptosis induced by Fas, Ca2+-ionophore, or thapsigargin; overexpression induces caspase-dependent apoptosis (suppressed by Z-VAD and Bcl-XL) and increases Aβ42 production in cells expressing APPsw, with potentiation by presenilin 2. Antisense oligonucleotide knockdown, overexpression, caspase inhibitor treatment, DNA ladder/cell morphology assays, Aβ ELISA FASEB journal Medium 11259376
2001 Mouse calsenilin/DREAM/KChIP3 is encoded by a single unique gene; alternate translation starts and alternative splicing yield multiple isoforms including some lacking EF-hand domains. Expression is restricted to the nervous system and largely coincides with Kv4.2 distribution. Full-length cDNA cloning, genomic analysis, in situ hybridization, RT-PCR, Northern blotting Molecular and cellular neurosciences Medium 11161465
2008 DREAM (KCNIP3) functions as a negative regulator of CREB-dependent transcription in a Ca2+-dependent manner; loss of DREAM in dream−/− mice enhances CREB-dependent transcription during learning, resulting in markedly enhanced learning, synaptic plasticity, and protection from brain aging. Genetic knockout mouse model, behavioral testing (contextual learning), synaptic plasticity assays, molecular analysis of CREB activity Current biology Medium 19110430
2009 KChIP3 membrane association and interaction with Kv4.2 is significantly decreased while nuclear KChIP3 is increased 6 hours after contextual fear conditioning training. Prodynorphin mRNA is decreased in WT but not KChIP3 KO mice after training, demonstrating KChIP3/DREAM transcriptional repression of prodynorphin during memory consolidation. KChIP3 KO mouse behavioral testing (fear conditioning), subcellular fractionation, co-immunoprecipitation with Kv4.2, RT-PCR for prodynorphin mRNA Learning & memory Medium 19223600
2009 DREAM directly interacts with the TSH receptor (TSHR) through a protein-protein interaction that promotes coupling between TSHR and Gαs; DREAM overexpression in transgenic mice causes marked thyroid enlargement, and elevated DREAM protein is found in human multinodular goiters. Co-immunoprecipitation (DREAM-TSHR interaction), transgenic mouse model, immunohistochemistry of human goiter tissue Molecular endocrinology Medium 19299442
2010 DREAM directly binds to the C0 domain of the NMDAR NR1 subunit; residues 21–40 of the DREAM N-terminus constitute the primary NR1 binding site and DREAM overexpression reduces surface NMDAR expression and NMDAR-mediated current, providing neuroprotection against excitotoxicity. Co-immunoprecipitation, pull-down assays, whole-cell patch-clamp electrophysiology, cell-permeable peptide (TAT-21-40) in vitro and in vivo neuroprotection assays The Journal of neuroscience Medium 20519532
2010 KChIP3 is specifically required for Ca2+-regulated secretion in PC12 cells; KChIP3 (but not KChIPs 1, 2, or 4) increases evoked exocytosis following purinergic receptor activation, delays Ca2+ recovery after peak elevation, and downregulates the Na+/Ca2+ exchanger NCX3 via its DREAM transcriptional repressor function. Overexpression of individual KChIP isoforms in PC12 cells, secretion assays, Ca2+ imaging, Western blot for NCX3 The Biochemical journal Medium 18393943
2010 Sumoylation regulates the nuclear localization of DREAM; DREAM interacts with the SUMO-conjugating enzyme Ubc9, and mutations at K26 and K90 prevent DREAM sumoylation and reduce nuclear localization without affecting DRE binding. Sumoylated DREAM is exclusively nuclear in PC12 cells and accumulates in the nucleus upon neuronal differentiation. Yeast two-hybrid (Ubc9 interaction), in vitro sumoylation assays with K-to-R point mutants, subcellular fractionation, immunofluorescence co-localization Biochimica et biophysica acta Medium 21070824
2009 DREAM represses prodynorphin and BDNF expression in the spinal cord; transgenic mice overexpressing a Ca2+- and cAMP-insensitive DREAM mutant show reduced spinal BDNF expression and fail to develop spinal sensitization following peripheral inflammation, demonstrating DREAM-dependent regulation of BDNF is required for central sensitization. Transgenic mouse overexpressing dominant-active DREAM, gene expression analysis (prodynorphin, BDNF), in vivo and in vitro spinal cord reflex assays Molecular pain Medium 21167062
2009 DREAM modulates cortical astrogliogenesis via a PACAP-cAMP-Ca2+-DREAM signaling cascade; PACAP stimulates cAMP production and Ca2+ entry, and Ca2+ in turn activates DREAM binding to the GFAP promoter DRE sequence to stimulate GFAP expression during astrocyte differentiation. Loss of DREAM in vivo alters the number of neurons and astrocytes generated during development. Reporter gene assays for GFAP promoter, DREAM knockout analysis, in vitro calcium and cAMP manipulation Molecular neurobiology Medium 19238593
2010 KChIP2, KChIP3, and KChIP4 all co-immunoprecipitate with Kv4.2 in adult mouse cortex. Loss of KChIP3 alone modestly reduces IA density in cortical pyramidal neurons, but combined knockdown of KChIP2, 3, and 4 markedly reduces IA and induces Kv current remodeling, revealing interdependent roles of KChIP subunits. Co-immunoprecipitation from mouse cortex, whole-cell patch-clamp in KO neurons, RNAi knockdown of multiple KChIPs The Journal of neuroscience Medium 20943905
2014 KChIP3 (KCNIP3) acts as a tonic brake on baseline mucin secretion in colonic goblet cells; KChIP3 associates with mature mucin-filled secretory granules, and ryanodine receptor-dependent intracellular Ca2+ oscillations dissociate KChIP3 from granules to allow exocytosis. Loss of KChIP3 (Kcnip3−/− mice or KD) causes mucin hypersecretion; overexpression or abolishing Ca2+-sensing increases granule association and inhibits baseline secretion. Kcnip3−/− mice (colon phenotype), human differentiated colonic cell line knockdown and overexpression, co-localization with mucin granules, Ca2+ imaging with ryanodine receptor manipulation eLife High 30272559
2014 NS5806 binds at a hydrophobic site on the C-terminus of KChIP3 in a Ca2+-dependent manner (Kd 2–5 µM in Ca2+-bound form) and increases the affinity of KChIP3 for the hydrophobic N-terminus of Kv4.3. Mutation of Tyr-174 or Phe-218 on KChIP3 abolishes this drug-induced enhancement of Kv4.3 binding. Fluorescence spectroscopy, isothermal titration calorimetry, docking simulations, site-directed mutagenesis of KChIP3 The Journal of biological chemistry Medium 25228688
2018 The N-terminal 31–50 fragment of KChIP3 binds directly to both the intracellular N- and C-termini of TRPV1, reducing TRPV1 surface localization and Ca2+ influx. A cell-permeable TAT-31-50 peptide reduces TRPV1-mediated Ca2+ influx in DRG neurons and alleviates thermal hyperalgesia in a CFA-induced inflammatory pain model, independently of endogenous KChIP3. Co-IP/pull-down mapping of KChIP3-TRPV1 interaction domain, surface TRPV1 biotinylation assay, Ca2+ imaging in DRG neurons, intrathecal/intraplantar TAT peptide injection in Kcnip3−/− and WT rats The Journal of neuroscience High 29335353
2021 DREAM (KCNIP3) in neutrophils promotes neutrophil recruitment to sites of TNF-α-induced vascular inflammation; DREAM represses expression of A20 (a NF-κB negative regulator) and enhances IKKβ phosphorylation and pro-inflammatory molecule expression after TNF-α stimulation. DREAM-dependent IKKβ activation mediates SNAP-23 phosphorylation and degranulation. Sickle cell disease mice lacking DREAM show reduced vaso-occlusive events. Intravital microscopy, genetic DREAM knockout in mice, pharmacological IKKβ inhibition, SNAP-23 phosphorylation assays, β2 integrin activity assay, HL-60 cell knockdown The Journal of experimental medicine High 34751735
2022 DREAM represses A20 (TNFAIP3) expression in fibroblasts; DREAM-null mice have elevated A20 and are protected from fibrosis, while mice with fibroblast-specific A20 deletion develop SSc-like fibrosis. TGF-β induces A20 expression in DREAM-null but not WT fibroblasts, establishing a DREAM-A20 regulatory axis governing fibroblast activation and organ fibrosis. DREAM-null mouse model, fibroblast-specific A20 conditional KO, A20 expression analysis, TGF-β stimulation assays, bleomycin fibrosis model Nature communications High 36289219
2019 Global Kcnip3 knockout in rats enhances pain sensitivity in both acute nociceptive and chronic inflammatory pain models and exacerbates negative emotions (anxiety, depression-like behavior, pain aversion). Transcriptomic profiling of KO rat forebrain reveals upregulation of genes associated with dopamine neurotransmission and neural development. CRISPR-generated Kcnip3−/− rat model, nociceptive behavioral testing, affective/anxiety behavioral tests, RNA-seq transcriptomic profiling, qPCR validation Frontiers in molecular neuroscience Medium 30740043
2016 FMRP mediates chronic ethanol-induced changes in KChIP3 expression in the hippocampus; chronic intermittent ethanol increases phosphorylation of FMRP at S499 (via S6K1), reduces KChIP3 protein while increasing KChIP3 mRNA association with FMRP, and S6K1 inhibition prevents these changes, indicating FMRP translational suppression of KChIP3 is part of homeostatic plasticity. In vivo CIE exposure, immunoblot, FMRP-bound mRNA immunoprecipitation, S6K1 inhibitor treatment in hippocampal slice cultures Alcoholism, clinical and experimental research Medium 27147118

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2017 Cell cycle arrest through indirect transcriptional repression by p53: I have a DREAM. Cell death and differentiation 526 29125603
1999 DREAM is a Ca2+-regulated transcriptional repressor. Nature 476 10078534
2015 The p53-p21-DREAM-CDE/CHR pathway regulates G2/M cell cycle genes. Nucleic acids research 280 26384566
2016 Integration of TP53, DREAM, MMB-FOXM1 and RB-E2F target gene analyses identifies cell cycle gene regulatory networks. Nucleic acids research 268 27280975
2011 DYRK1A protein kinase promotes quiescence and senescence through DREAM complex assembly. Genes & development 249 21498570
2001 Tuning pacemaker frequency of individual dopaminergic neurons by Kv4.3L and KChip3.1 transcription. The EMBO journal 246 11598014
2021 Dream: powerful differential expression analysis for repeated measures designs. Bioinformatics (Oxford, England) 229 32730587
2007 Dialogue on reverse-engineering assessment and methods: the DREAM of high-throughput pathway inference. Annals of the New York Academy of Sciences 224 17925349
2017 Cell cycle transcription control: DREAM/MuvB and RB-E2F complexes. Critical reviews in biochemistry and molecular biology 197 28799433
2017 Angiogenic gene therapy in cardiovascular diseases: dream or vision? European heart journal 144 28073865
2014 Circulating tumor cells and circulating tumor DNA for precision medicine: dream or reality? Annals of oncology : official journal of the European Society for Medical Oncology 120 25336116
2005 Multiprotein assembly of Kv4.2, KChIP3 and DPP10 produces ternary channel complexes with ISA-like properties. The Journal of physiology 116 16123112
2021 Allogeneic CAR Cell Therapy-More Than a Pipe Dream. Frontiers in immunology 106 33488631
2001 Calcium-regulated DNA binding and oligomerization of the neuronal calcium-sensing protein, calsenilin/DREAM/KChIP3. The Journal of biological chemistry 105 11535596
2024 Molecular glues for protein-protein interactions: Progressing toward a new dream. Cell chemical biology 100 38701786
2015 Structural mechanisms of DREAM complex assembly and regulation. Genes & development 97 25917549
2019 DREAM and RB cooperate to induce gene repression and cell-cycle arrest in response to p53 activation. Nucleic acids research 94 31400114
2016 Targeting the PD-1/PD-L1 axis in multiple myeloma: a dream or a reality? Blood 92 27919908
2005 Mg2+ and Ca2+ differentially regulate DNA binding and dimerization of DREAM. The Journal of biological chemistry 92 15746104
2017 Human papilloma virus E7 oncoprotein abrogates the p53-p21-DREAM pathway. Scientific reports 88 28572607
2002 L-arginine in cardiovascular disease: dream or reality? Vascular medicine (London, England) 69 12553744
2001 Pro-apoptotic function of calsenilin/DREAM/KChIP3. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 65 11259376
2022 Association Between Depression and Severity of Dry Eye Symptoms, Signs, and Inflammatory Markers in the DREAM Study. JAMA ophthalmology 63 35266971
2010 The DREAM protein negatively regulates the NMDA receptor through interaction with the NR1 subunit. The Journal of neuroscience : the official journal of the Society for Neuroscience 63 20519532
2009 Lentiviral vectors with measles virus glycoproteins - dream team for gene transfer? Trends in biotechnology 57 19327858
2008 Vaccine adjuvants: the dream becomes real. Human vaccines 55 18682690
2001 Mouse DREAM/calsenilin/KChIP3: gene structure, coding potential, and expression. Molecular and cellular neurosciences 55 11161465
2018 The cell cycle regulatory DREAM complex is disrupted by high expression of oncogenic B-Myb. Oncogene 54 30206359
2004 Induction of pro-apoptotic calsenilin/DREAM/KChIP3 in Alzheimer's disease and cultured neurons after amyloid-beta exposure. Journal of neurochemistry 54 14720210
2015 The DREAM complex promotes gene body H2A.Z for target repression. Genes & development 52 25737279
2021 PAF remodels the DREAM complex to bypass cell quiescence and promote lung tumorigenesis. Molecular cell 50 33626321
2009 The role of calsenilin/DREAM/KChIP3 in contextual fear conditioning. Learning & memory (Cold Spring Harbor, N.Y.) 50 19223600
2021 TMB in NSCLC: A Broken Dream? International journal of molecular sciences 49 34207126
2020 Antibodies for the Treatment of Brain Metastases, a Dream or a Reality? Pharmaceutics 49 31940974
2010 Interdependent roles for accessory KChIP2, KChIP3, and KChIP4 subunits in the generation of Kv4-encoded IA channels in cortical pyramidal neurons. The Journal of neuroscience : the official journal of the Society for Neuroscience 49 20943905
2023 The DREAM complex functions as conserved master regulator of somatic DNA-repair capacities. Nature structural & molecular biology 48 36959262
2008 Lack of DREAM protein enhances learning and memory and slows brain aging. Current biology : CB 48 19110430
2020 DREAM complex suppresses DNA methylation maintenance genes and precludes DNA hypermethylation. Nature plants 44 32661276
2001 Ca2+-dependent transcriptional repression and derepression: DREAM, a direct effector. Seminars in cell & developmental biology 44 11162748
2021 Advances in systems biology modeling: 10 years of crowdsourcing DREAM challenges. Cell systems 43 34139170
2021 Cancer Vaccines: Promising Therapeutics or an Unattainable Dream. Vaccines 43 34207062
2020 Multiple Myeloma DREAM Challenge reveals epigenetic regulator PHF19 as marker of aggressive disease. Leukemia 43 32060406
2023 Key elements of cellular senescence involve transcriptional repression of mitotic and DNA repair genes through the p53-p16/RB-E2F-DREAM complex. Aging 39 37219418
2004 KChIP3 rescues the functional expression of Shal channel tetramerization mutants. The Journal of biological chemistry 37 15485870
2021 DREAM On: Cell Cycle Control in Development and Disease. Annual review of genetics 36 34496610
2024 The concept of gene therapy for glaucoma: the dream that has not come true yet. Neural regeneration research 35 37488850
2014 DNA testing for malignant hyperthermia: the reality and the dream. Anesthesia and analgesia 34 24445638
2006 Adult stem cell therapy: dream or reality? Transplant immunology 34 17157222
2021 Neutrophil DREAM promotes neutrophil recruitment in vascular inflammation. The Journal of experimental medicine 32 34751735
2018 Checkpoint-inhibition in ovarian cancer: rising star or just a dream? Journal of gynecologic oncology 31 30207101
2014 Modulation of the voltage-gated potassium channel (Kv4.3) and the auxiliary protein (KChIP3) interactions by the current activator NS5806. The Journal of biological chemistry 31 25228688
2012 Pharma-metabolomics in neonatology: is it a dream or a fact? Current pharmaceutical design 31 22564294
2022 Disrupting the DREAM complex enables proliferation of adult human pancreatic β cells. The Journal of clinical investigation 30 35700053
2018 The HDAC-Associated Sin3B Protein Represses DREAM Complex Targets and Cooperates with APC/C to Promote Quiescence. Cell reports 30 30517867
2013 Molecular classification of colorectal cancer: a dream that can become a reality. Romanian journal of morphology and embryology = Revue roumaine de morphologie et embryologie 30 23771065
2022 Shorter antibiotic courses in the immunocompromised: the impossible dream? Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases 29 35988852
2020 Cardiac Regeneration: New Hope for an Old Dream. Annual review of physiology 29 33064963
2019 The Dream of a Mycobacterium. Microbiology spectrum 29 31025625
2014 Loss of the mammalian DREAM complex deregulates chondrocyte proliferation. Molecular and cellular biology 27 24710275
2014 Do endothelial cells dream of eclectic shape? Developmental cell 26 24780735
2021 PD-L1 expression as a predictive biomarker for immune checkpoint inhibitors: between a dream and a nightmare. Immunotherapy 24 34190579
2018 DREAM-Dependent Activation of Astrocytes in Amyotrophic Lateral Sclerosis. Molecular neurobiology 24 28840473
2010 Sumoylation regulates nuclear localization of repressor DREAM. Biochimica et biophysica acta 24 21070824
2017 The Endocannabinoid System Modulating Levels of Consciousness, Emotions and Likely Dream Contents. CNS & neurological disorders drug targets 23 28240187
2014 dREAM co-operates with insulator-binding proteins and regulates expression at divergently paired genes. Nucleic acids research 23 25053843
2009 PACAP signaling to DREAM: a cAMP-dependent pathway that regulates cortical astrogliogenesis. Molecular neurobiology 22 19238593
2009 The DREAM protein is associated with thyroid enlargement and nodular development. Molecular endocrinology (Baltimore, Md.) 22 19299442
2022 Fibroblast A20 governs fibrosis susceptibility and its repression by DREAM promotes fibrosis in multiple organs. Nature communications 21 36289219
2021 LIN37-DREAM prevents DNA end resection and homologous recombination at DNA double-strand breaks in quiescent cells. eLife 21 34477552
2024 The p21CIP1-CDK4-DREAM axis is a master regulator of genotoxic stress-induced cellular senescence. Nucleic acids research 20 38783095
2023 Daring to dream: Targeting lipoprotein(a) as a causal and risk-enhancing factor. Pharmacological research 20 37406784
2021 Progesterone Receptors Promote Quiescence and Ovarian Cancer Cell Phenotypes via DREAM in p53-Mutant Fallopian Tube Models. The Journal of clinical endocrinology and metabolism 20 33755733
2018 KChIP3 N-Terminal 31-50 Fragment Mediates Its Association with TRPV1 and Alleviates Inflammatory Hyperalgesia in Rats. The Journal of neuroscience : the official journal of the Society for Neuroscience 20 29335353
2010 Increased B cell proliferation and reduced Ig production in DREAM transgenic mice. Journal of immunology (Baltimore, Md. : 1950) 20 21059893
2010 DREAM regulates BDNF-dependent spinal sensitization. Molecular pain 20 21167062
2023 Novel technologies are turning a dream into reality: conditionally replicating viruses as vaccines. Trends in microbiology 19 37798168
2018 Review: Limb regeneration in humans: Dream or reality? Annals of anatomy = Anatomischer Anzeiger : official organ of the Anatomische Gesellschaft 19 29408367
2017 Organ reconstruction: Dream or reality for the future. Bio-medical materials and engineering 19 28372287
2020 Monoclonal Antibodies to Treat Multiple Myeloma: A Dream Come True. International journal of molecular sciences 18 33139668
2019 Electroacupuncture regulates the DREAM/NF-κB signalling pathway and ameliorates cyclophosphamide-induced immunosuppression in mice. Acupuncture in medicine : journal of the British Medical Acupuncture Society 18 31192694
2018 KChIP3 coupled to Ca2+ oscillations exerts a tonic brake on baseline mucin release in the colon. eLife 18 30272559
2016 Capturing Darwin's dream. Molecular ecology resources 18 27454358
2014 Is personalized medicine a dream or a reality? Critical reviews in clinical laboratory sciences 18 25181036
2022 Therapeutic Potential of VEGF-B in Coronary Heart Disease and Heart Failure: Dream or Vision? Cells 17 36552897
2016 FMRP Mediates Chronic Ethanol-Induced Changes in NMDA, Kv4.2, and KChIP3 Expression in the Hippocampus. Alcoholism, clinical and experimental research 17 27147118
2023 Vaccinal effect of HIV-1 antibody therapy: dream or reality? Current opinion in HIV and AIDS 16 37144564
2022 Plasmodium vivax Duffy Binding Protein-Based Vaccine: a Distant Dream. Frontiers in cellular and infection microbiology 16 35909975
2021 p53-Dependent Repression: DREAM or Reality? Cancers 16 34638334
2021 DREAM represses distinct targets by cooperating with different THAP domain proteins. Cell reports 16 34686342
2021 DREAM: a database of experimentally supported protein-coding RNAs and drug associations in human cancer. Molecular cancer 16 34774049
2015 The association of mammalian DREAM complex and HPV16 E7 proteins. American journal of cancer research 16 26885443
2003 Reduced expression of calsenilin/DREAM/KChIP3 in the brains of kainic acid-induced seizure and epilepsy patients. Neuroscience letters 16 12648752
2024 PCLAF-DREAM drives alveolar cell plasticity for lung regeneration. Nature communications 15 39448571
2022 RBL2/DREAM-mediated repression of the Aurora kinase A/B pathway determines therapy responsiveness and outcome in p53 WT NSCLC. Scientific reports 15 35058503
2019 Global Gene Knockout of Kcnip3 Enhances Pain Sensitivity and Exacerbates Negative Emotions in Rats. Frontiers in molecular neuroscience 15 30740043
2009 Universal species concept: pipe dream or a step toward unifying biology? Journal of industrial microbiology & biotechnology 15 19779746
2021 Untapped endocannabinoid pharmacological targets: Pipe dream or pipeline? Pharmacology, biochemistry, and behavior 14 33932409
2008 Specific effects of KChIP3/calsenilin/DREAM, but not KChIPs 1, 2 and 4, on calcium signalling and regulated secretion in PC12 cells. The Biochemical journal 14 18393943
2007 Lipid rafts: dream or reality for cholesterol transporters? European biophysics journal : EBJ 14 17576551
2024 HDAC activity is dispensable for repression of cell-cycle genes by DREAM and E2F:RB complexes. Nature communications 13 38789411

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