Affinage

RCAN1

Calcipressin-1 · UniProt P53805

Length
252 aa
Mass
28.1 kDa
Annotated
2026-06-10
100 papers in source corpus 44 papers cited in narrative 42 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

RCAN1 (DSCR1) is an endogenous regulator of the Ca2+/calmodulin-dependent phosphatase calcineurin that governs the calcineurin–NFAT signaling axis across cardiovascular, neuronal, immune, and metabolic contexts (PMID:10861295, PMID:19458618, PMID:18455125, PMID:19124655). It binds calcineurin A directly at the linker region between the catalytic and calcineurin-B-binding domains, and a short peptide spanning its conserved calcineurin-interacting region competitively inhibits phosphatase activity, blocking NFAT dephosphorylation, nuclear translocation, and transcription (PMID:10861295, PMID:16131541). Loss of RCAN1 elevates calcineurin activity in vivo, producing excess substrate dephosphorylation and phenotypes from defective spatial learning and late-phase LTP to hyperactivated endothelial and mast-cell signaling (PMID:18045910, PMID:19124655, PMID:19458618, PMID:18455125). Its activity is not fixed but switched by phosphorylation: Dyrk1A phosphorylation at Thr192 strengthens calcineurin binding and inhibition while extending RCAN1 half-life, whereas TAK1 phosphorylation at Ser94/Ser136—following RCAN1 binding to TAB2 and recruitment of a TAK1–TAB1–calcineurin complex—and GSK3β nuclear export convert RCAN1 from inhibitor to facilitator of NFAT signaling; oxidative-stress-induced phosphorylation of its conserved region attenuates inhibition (PMID:19136967, PMID:21965663, PMID:21172821, PMID:12927602). RCAN1 abundance is set by opposing post-translational controls—neddylation at K96/K104/K107 stabilizes and potentiates it, while SCFβ-TrCP ubiquitination, CREB-driven proteasomal turnover, and chaperone-mediated autophagy degrade it—and by isoform-specific transcription through ATF6, C/EBPβ/NFAT feedback, Egr1, glucocorticoid response elements, and DNMT-mediated methylation (PMID:23118980, PMID:18575781, PMID:18485898, PMID:19509306, PMID:18319259, PMID:20371871, PMID:19124655, PMID:21216952, PMID:31285763). Functionally, RCAN1 dosage controls tumor and developmental angiogenesis via endothelial calcineurin-NFAT and VEGFR-2 trafficking (PMID:19458618, PMID:18455125, PMID:15016650, PMID:28271280), restrains calcineurin-dependent DRP1 activation to preserve mitochondrial fusion (PMID:29362227), and cooperates with DYRK1A to suppress NFATc during neocortical development, a Down syndrome-relevant circuit (PMID:16554754, PMID:24352425). Beyond calcineurin, RCAN1 interacts with FMRP to regulate dendritic spine morphology and local protein synthesis, with TET1 to control miR-124-dependent adult neurogenesis, and modulates vesicle fusion-pore kinetics in a partially calcineurin-independent manner (PMID:22863780, PMID:31304631, PMID:18180251). RCAN1 dysregulation drives calcineurin-dependent disease, including Down syndrome neurotrophin-trafficking and differentiation deficits, Alzheimer's-associated tau hyperphosphorylation through combined calcineurin inhibition and GSK3β upregulation, and Huntington's striatal neurodegeneration where RCAN1 knockdown restores calcineurin-TFEB-autophagy signaling (PMID:26658127, PMID:21876249, PMID:38066314).

Mechanistic history

Synthesis pass · year-by-year structured walk · 21 steps
  1. 2000 High

    Established that RCAN1 is a direct calcineurin-binding inhibitor, defining its core molecular activity and the calcineurin-NFAT axis it controls.

    Evidence Co-IP, calcineurin phosphatase assay, and NFAT translocation assay with overexpression in cell lines

    PMID:10861295

    Open questions at the time
    • Binding region mapped to the calcineurin linker but no structural model of the complex
    • Endogenous regulation not yet addressed by overexpression alone
  2. 2002 High

    Showed that RCAN1-mediated calcineurin inhibition is cytoprotective, linking abundance to resistance against oxidative and calcium stress.

    Evidence Stable and inducible transgene plus antisense knockdown in HA-1/PC-12 cells under H2O2 and ionophore challenge

    PMID:12039863

    Open questions at the time
    • Protective downstream effectors not defined
    • Isoform-specific contributions not separated
  3. 2005 High

    Defined the minimal inhibitory unit, showing a short RCAN1 peptide competitively blocks calcineurin, supporting a defined enzymatic mechanism.

    Evidence In vitro and in vivo phosphatase and NFAT localization assays with peptide fragment

    PMID:15935327 PMID:16131541

    Open questions at the time
    • Raf-1 binding (15935327) lacks a defined functional consequence
    • Competition mode versus the full-length protein not fully resolved
  4. 2004 High

    Placed RCAN1 in a VEGF-driven endothelial negative-feedback loop, establishing a physiological inducer and an anti-inflammatory role for its calcineurin inhibition.

    Evidence Genome-wide expression, overexpression, and siRNA knockdown in endothelial cells with NFAT and inflammatory gene readouts

    PMID:15016650

    Open questions at the time
    • Promoter elements driving VEGF induction not mapped here
    • In vivo vascular relevance addressed only later
  5. 2006 High

    Demonstrated cooperative dosage effects of RCAN1 and DYRK1A on NFATc, providing a quantitative model for how trisomy destabilizes calcineurin-NFAT signaling.

    Evidence Mathematical modeling validated in calcineurin/Nfatc-deficient, overexpressing, and Down syndrome mouse models

    PMID:16554754

    Open questions at the time
    • Direct biochemical interplay of the two gene products not dissected
    • Tissue-specific thresholds not defined
  6. 2006 High

    Connected RCAN1 to tau pathology, showing it both inhibits calcineurin and upregulates GSK3β to promote tau phosphorylation and block proteasomal tau degradation.

    Evidence Tet-off RCAN1 transgene in PC12 cells, in vitro 20S proteasome degradation assay, GSK3β analysis, and human brain correlation

    PMID:16649988 PMID:16939415

    Open questions at the time
    • Mechanism of post-transcriptional GSK3β upregulation unresolved
    • In vivo tau consequences not yet tested
  7. 2008 Medium

    Identified transcriptional and ubiquitin-proteasome controls of RCAN1 abundance, showing ATF6 induces it and CREB and SCFβ-TrCP target it for degradation.

    Evidence ATF6 transgenic mice and promoter assays; proteasome inhibitor, ubiquitination, pulse-chase, and in vitro SCFβ-TrCP reconstitution

    PMID:18319259 PMID:18485898 PMID:18575781

    Open questions at the time
    • Interplay between competing degradation routes not integrated
    • Single-lab biochemistry for several degradation findings
  8. 2003 Medium

    Showed oxidative stress phosphorylates the conserved calcineurin-interacting region of RCAN1, attenuating inhibition and defining redox-sensitive regulation of activity.

    Evidence Oxidant treatment, gel mobility shift, kinase inhibitor panel, and phosphopeptide calcineurin assays

    PMID:12927602

    Open questions at the time
    • Responsible kinase(s) not definitively assigned
    • Phosphosite stoichiometry in cells unquantified
  9. 2007 High

    Provided genetic proof that endogenous RCAN1 restrains calcineurin in the brain, linking its loss to substrate hyperdephosphorylation and learning/LTP deficits.

    Evidence RCAN1 KO mice with calcineurin activity, DARPP-32 phosphorylation, behavioral, and electrophysiology assays

    PMID:18045910

    Open questions at the time
    • Cell types responsible for behavioral deficits not isolated
    • Cleaved calcineurin fragment origin unexplained
  10. 2009 High

    Revealed the TAK1-driven inhibitor-to-facilitator switch, showing RCAN1–TAB2 recruits a TAK1–TAB1–calcineurin complex and Ser94/Ser136 phosphorylation reverses RCAN1's role.

    Evidence Yeast two-hybrid, in vitro binding and kinase assays, mutagenesis, KO MEFs, and NFAT reporter in cardiomyocyte hypertrophy

    PMID:19136967

    Open questions at the time
    • In vivo cardiac requirement of the switch not established here
    • Structural basis of the multiprotein complex unknown
  11. 2009 Medium

    Extended RCAN1 turnover control to chaperone-mediated autophagy and broadened its immune role as an Egr1-controlled brake on FcεRI-mediated mast cell activation.

    Evidence CMA/lysosome inhibitor and motif analysis; Rcan1 KO mast cells with reconstitution, calcineurin/NFAT/NF-κB readouts, ChIP, and anaphylaxis model

    PMID:19124655 PMID:19509306

    Open questions at the time
    • Relative flux through CMA versus proteasome in vivo unclear
    • Direct NF-κB regulation mechanism not fully defined
  12. 2011 High

    Mapped Dyrk1A and GSK3β phosphorylation as the molecular tuner of RCAN1, with Thr192 enhancing calcineurin inhibition and GSK3β nuclear export enabling the facilitatory state.

    Evidence In vitro kinase assays, mutagenesis, Co-IP, calcineurin/NFAT assays, single-cell modeling, and PI3K inhibition

    PMID:21172821 PMID:21965663

    Open questions at the time
    • Quantitative thresholds dictating inhibitor versus facilitator state in vivo unknown
    • Cross-talk with TAK1-mediated switch not integrated
  13. 2011 Medium

    Linked stress-induced RCAN1-1 to neuronal apoptosis and tau pathology, showing a glucocorticoid response element and Aβ/oxidative-stress induction converge on caspase activation and tau hyperphosphorylation.

    Evidence Primary neuron overexpression and siRNA, caspase assays, caspase-3 KO rescue, GRE identification, and Aβ/antioxidant treatments

    PMID:21216952 PMID:21876249

    Open questions at the time
    • In vivo relevance to Alzheimer's progression not tested
    • Single-lab in vitro neuronal systems
  14. 2012 Medium

    Established neddylation as a stabilizing, potentiating modification and uncovered RCAN1 protein-protein roles beyond calcineurin via FMRP at dendritic spines and CREB-Bcl-2 survival signaling.

    Evidence NEDD8 site mapping and stability/binding assays; FMRP Co-IP with spine and local-synthesis rescue; CREB/Bcl-2 reporter and H2O2 cytotoxicity assays

    PMID:21890628 PMID:22863780 PMID:23118980 PMID:23150431

    Open questions at the time
    • NEDD8 conjugating machinery for RCAN1 not identified
    • FMRP-dependent function not mechanistically separated from calcineurin
  15. 2012 Medium

    Connected RCAN1 to mitochondrial and vesicular physiology, showing RCAN1-1L drives mitophagy/bioenergetic shift and that fusion-pore regulation is partly calcineurin-independent.

    Evidence Inducible RCAN1-1L in neuronal cells with ANT/mPTP and bioenergetic assays; chromaffin-cell amperometry in KO/overexpressing mice

    PMID:18180251 PMID:22389495

    Open questions at the time
    • Calcineurin-independent fusion-pore effector unidentified
    • Mechanism coupling RCAN1 to ANT/mPTP unresolved
  16. 2013 Medium

    Demonstrated developmental and atherosclerotic roles, with RCAN1/DYRK1A suppressing NFATc in neocortical progenitors and RCAN1 regulating macrophage CD36 and oxLDL uptake.

    Evidence In utero electroporation and Ts1Cje rescue; Apoe-/-Rcan1-/- mice with bone marrow transplantation and CD36/oxLDL assays

    PMID:24127415 PMID:24352425

    Open questions at the time
    • Direct calcineurin dependence of CD36 regulation not established
    • Neuronal versus vascular dosage effects not unified
  17. 2015 High

    Showed RCAN1 dosage controls NGF/TrkA neurotrophin trafficking and, when overexpressed, drives DRP1-mediated fission with tau pathology, mechanistically linking it to Down syndrome and tauopathy.

    Evidence Down syndrome mouse genetic correction with TrkA internalization and survival assays; brain-specific RCAN1.1S transgenic mice with DRP1, behavioral, and tau readouts

    PMID:26497675 PMID:26658127

    Open questions at the time
    • Mechanism by which RCAN1 controls receptor endocytosis only partly defined
    • Reconciliation of fission (overexpression) versus fusion (depletion) phenotypes incomplete
  18. 2016 Medium

    Extended RCAN1 mitochondrial control to β-cells, showing overexpression impairs oxidative phosphorylation, ATP production, and glucose-stimulated insulin exocytosis.

    Evidence RCAN1-overexpressing mice with in vivo insulin secretion, membrane potential, OXPHOS, ATP, and granule exocytosis assays

    PMID:27195491

    Open questions at the time
    • Calcineurin-dependence of the β-cell phenotype not isolated
    • Single-lab transgenic model
  19. 2017 High

    Resolved how RCAN1 maintains mitochondrial fusion by restraining calcineurin-dependent DRP1 activation, and broadened its signaling roles to VEGFR-2 trafficking and LRRK2-Tollip-NF-κB inflammation.

    Evidence RCAN1 KO/overexpressing cardiomyocytes with DS iPSC and pharmacological rescue; VEGFR-2 internalization and zebrafish morpholino; LRRK2 kinase, Co-IP, and NF-κB/IL-8 assays

    PMID:28271280 PMID:28553204 PMID:29362227

    Open questions at the time
    • LRRK2-RCAN1 inflammatory axis (28553204) single-lab and Medium-confidence
    • Direct DRP1 regulation versus calpain contribution not fully separated
  20. 2019 Medium

    Uncovered a calcineurin-independent epigenetic function whereby RCAN1 binds TET1 introns to regulate splicing and miR-124-dependent adult neurogenesis, and showed DNMT methylation silences RCAN1.4 in fibrosis.

    Evidence RCAN1 KO mice with splicing/methylation/neurogenesis assays and TET1 genetic rescue; ChIP/bisulfite analysis with AAV rescue in liver fibrosis

    PMID:31285763 PMID:31304631

    Open questions at the time
    • Biochemical basis of RCAN1 RNA-binding/splicing activity undefined
    • Relationship of TET1 role to calcineurin functions unknown
  21. 2023 High

    Demonstrated therapeutic relevance in neurodegeneration, showing RCAN1 knockdown enhances calcineurin-TFEB-autophagy signaling to rescue Huntington's patient-derived neurons, mimicked pharmacologically.

    Evidence Patient-derived reprogrammed MSNs with RCAN1 knockdown, calcineurin/TFEB and ATAC-seq readouts, and G2-115 disruption of RCAN1-calcineurin

    PMID:38066314

    Open questions at the time
    • In vivo efficacy of RCAN1-calcineurin disruption not established
    • Specificity of G2-115 for the RCAN1-calcineurin interface not fully characterized

Open questions

Synthesis pass · forward-looking unresolved questions
  • How RCAN1's calcineurin-dependent and calcineurin-independent activities (RNA/splicing with TET1, FMRP-linked local translation, fusion-pore kinetics) are coordinated, and what structural features encode the inhibitor-versus-facilitator switch, remain unresolved.
  • No structural model of the RCAN1-calcineurin complex or of the phosphorylation-dependent conformational switch
  • Molecular basis of RCAN1 nucleic-acid binding undefined
  • Quantitative rules governing dosage-dependent role reversal in vivo unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 4 GO:0140096 catalytic activity, acting on a protein 2 GO:0003723 RNA binding 1
Localization
GO:0005739 mitochondrion 3 GO:0005634 nucleus 1
Pathway
R-HSA-392499 Metabolism of proteins 4 R-HSA-1266738 Developmental Biology 3 R-HSA-162582 Signal Transduction 3 R-HSA-74160 Gene expression (Transcription) 3 R-HSA-168256 Immune System 2 R-HSA-1852241 Organelle biogenesis and maintenance 2 R-HSA-9612973 Autophagy 2
Partners
BTRCDYRK1AFMRPPPP3CARAF1TAB2TAK1TET1
Complex memberships
TAK1-TAB1-TAB2-calcineurin signaling complex

Evidence

Reading pass · 42 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2000 RCAN1 (DSCR1) protein physically interacts with and inhibits calcineurin A (the catalytic subunit of PP2B). The binding region on calcineurin A is located in the linker region between the catalytic domain and the calcineurin B binding domain. Overexpression of RCAN1 inhibits calcineurin-dependent NFAT nuclear translocation and transcriptional activation. Co-immunoprecipitation, calcineurin phosphatase activity assay, NFAT nuclear translocation assay, overexpression in cell lines Human molecular genetics High 10861295
2006 DSCR1 and DYRK1A act synergistically to prevent nuclear occupancy of NFATc transcription factors. Trisomy of both genes cooperatively destabilizes the calcineurin-NFAT regulatory circuit, leading to reduced NFATc activity. Mathematical modeling predicted that autoregulation within the pathway accentuates trisomy effects. Validated in calcineurin- and Nfatc-deficient mice, Dscr1- and Dyrk1a-overexpressing mice, and Down syndrome mouse models. Mathematical modeling, transgenic mouse models (Dscr1- and Dyrk1a-overexpressing), calcineurin/Nfatc knockout mice, Down syndrome mouse model analysis Nature High 16554754
2005 A small peptide fragment of DSCR1 competitively inhibits calcineurin phosphatase activity in vitro and in vivo, blocking calcineurin-mediated NFAT nuclear localization. In vitro calcineurin phosphatase activity assay, in vivo NFAT nuclear localization assay, peptide fragment analysis Proceedings of the National Academy of Sciences of the United States of America High 16131541
2009 RCAN1 interacts directly with TAB2, recruiting a macromolecular complex containing TAK1, TAB1, and calcineurin. TAK1 phosphorylates RCAN1 at Ser94 and Ser136, converting RCAN1 from an inhibitor to a facilitator of calcineurin-NFAT signaling. This enhances NFATc1 nuclear translocation and hypertrophic cardiomyocyte growth. Calcineurin activation conversely dephosphorylates and inhibits TAK1 and TAB1. Yeast two-hybrid screen, in vitro binding assay, Co-immunoprecipitation, in vitro phosphorylation assay, site-directed mutagenesis, Rcan1/2- and Tab2-deficient MEF cultures, calcineurin activity assay, NFAT transcriptional reporter Nature cell biology High 19136967
2011 Dyrk1A directly interacts with and phosphorylates RCAN1 at Ser112 and Thr192. Phosphorylation at Ser112 primes RCAN1 for GSK3β-mediated phosphorylation at Ser108. Phosphorylation at Thr192 enhances RCAN1 binding to calcineurin, increasing calcineurin inhibition, reducing NFAT transcriptional activity, and enhancing tau phosphorylation. Dyrk1A-mediated phosphorylation also extends RCAN1 half-life. In vitro kinase assay, site-directed mutagenesis, Co-immunoprecipitation, calcineurin phosphatase activity assay, NFAT reporter assay, Western blot of Dyrk1A transgenic mouse brain The Journal of biological chemistry High 21965663
2002 RCAN1 isoform 1 (calcipressin 1) protects against acute oxidative stress and calcium-mediated stress through calcineurin inhibition. Protection increased as a function of RCAN1 expression and decreased when expression was reduced via antisense oligonucleotides. Stable RCAN1 transfection in HA-1 cells, tet-off regulated RCAN1 transgene in PC-12 cells, antisense oligonucleotides, H2O2 and calcium ionophore challenge, cross-adaptation assay FASEB journal High 12039863
2009 DSCR1/RCAN1 overexpression suppresses tumor angiogenesis through inhibition of the calcineurin pathway in vascular endothelium, sufficient to suppress tumor growth in mice. Targeted deletion of both DSCR1 isoforms leads to hyperactivated calcineurin, precocious endothelial apoptosis, impaired tumor vasculature, and suppressed tumorigenesis. Calcineurin inhibition with cyclosporin A rescues this endothelial defect in DSCR1−/− mice. Transgenic Dscr1 mouse (single extra copy), DSCR1−/− knockout mice, tumor implantation models, cyclosporin A pharmacological rescue, VEGF-mediated calcineurin-NFAT pathway assays Nature / Cancer cell High 18455125 19458618
2004 DSCR1/RCAN1 expression in endothelial cells blocks dephosphorylation, nuclear translocation, and transcriptional activity of NFAT (downstream of calcineurin). DSCR1 is most significantly induced by VEGF in a genome-wide analysis. Knockdown of endogenous DSCR1 increases NFAT activity and stimulates inflammatory gene expression (tissue factor, E-selectin, Cox-2). Genome-wide gene expression analysis, DSCR1 overexpression in endothelial cells, NFAT nuclear translocation assay, siRNA knockdown of DSCR1, inflammatory marker gene expression Blood High 15016650
2007 RCAN1 knockout mice exhibit increased calcineurin enzymatic activity, increased abundance of a cleaved calcineurin fragment, decreased phosphorylation of DARPP-32 (a calcineurin substrate), and deficits in spatial learning, associative memory, and late-phase LTP—phenotypes consistent with excess calcineurin signaling. RCAN1 knockout mouse, calcineurin activity assay, DARPP-32 phosphorylation western blot, behavioral testing (Morris water maze, fear conditioning), electrophysiology (L-LTP) The Journal of neuroscience High 18045910
2009 RCAN1 protein is degraded by both the ubiquitin-proteasome pathway and chaperone-mediated autophagy (CMA) through a CMA-lysosome pathway. Two CMA recognition motifs were identified in RCAN1. Inhibition of CMA increased RCAN1 expression. Inhibition of RCAN1 degradation reduced calcineurin-NFAT activity. Lysosomal inhibitors, macroautophagy inhibition, CMA disruption, promoter assay for calcineurin-NFAT activity, identification of CMA recognition motifs FASEB journal Medium 19509306
2008 RCAN1 is a novel ATF6-inducible gene. Activated ATF6 induces the RCAN1 promoter, upregulates RCAN1 mRNA, inhibits calcineurin phosphatase activity, and exerts a growth-modulating effect in cardiac myocytes that is blocked by RCAN1-targeted siRNA. Transgenic ATF6 mouse model, transcript profiling, adenoviral ATF6 overexpression in cardiac myocytes, RCAN1 promoter-luciferase assay, calcineurin activity assay, siRNA knockdown The Journal of biological chemistry High 18319259
2006 RCAN1 overexpression (via tet-off RCAN1 transgene) inhibits calcineurin (PP2B), leading to increased tau phosphorylation by GSK3β and significantly inhibiting tau degradation by the proteasome in PC12 cells. Tet-off RCAN1 transgene in PC12 cells, in vitro 20S proteasome degradation assay with recombinant tau, GSK3β phosphorylation assay, okadaic acid and cyclosporin A pharmacological comparisons The Biochemical journal High 16939415
2006 Regulated overexpression of an RCAN1 transgene stimulates expression of GSK3β kinase at a post-transcriptional level. RCAN1-1S isoform levels specifically correlate with GSK3β levels in human brain. This positions RCAN1 as a regulator of both calcineurin and the opposing kinase GSK3β. Regulated RCAN1 transgene expression, Western blotting for GSK3β protein, mRNA analysis (post-transcriptional mechanism), human brain tissue analysis The FEBS journal Medium 16649988
2011 Amyloid-β upregulates RCAN1 expression in cortical neurons via Aβ-induced oxidative stress. Increased RCAN1 both inhibits calcineurin (reducing tau dephosphorylation) and upregulates GSK3β (increasing tau phosphorylation), together causing tau hyperphosphorylation. Silencing RCAN1 or adding antioxidants prevented Aβ-induced tau hyperphosphorylation. Primary fetal rat cortical neuron culture with Aβ treatment, RCAN1 siRNA knockdown, antioxidant treatment, tau phosphorylation western blot, calcineurin activity assay, GSK3β expression analysis Journal of Alzheimer's disease Medium 21876249
2011 RCAN1-1 overexpression in primary neurons activates caspase-9 and caspase-3, inducing neuronal apoptosis. A functional glucocorticoid response element was identified in the RCAN1 isoform 1 promoter mediating stress-induced upregulation. Neurotoxicity of RCAN1-1 is blocked in caspase-3−/− neurons. Overexpression in primary neurons, caspase-3/9 activation assay, caspase-3 knockout neurons, glucocorticoid response element identification in RCAN1-1 promoter, dexamethasone treatment The Journal of biological chemistry Medium 21216952
2008 RCAN1 regulates vesicle exocytosis in chromaffin cells: Rcan1 loss or overexpression both reduced the number of vesicles undergoing exocytosis. Increasing Rcan1 expression reduced catecholamine released per vesicle and altered fusion pore kinetics. Acute calcineurin inhibition did not replicate the effect of RCAN1 overexpression, indicating a calcineurin-independent mechanism for fusion pore regulation. RCAN1 overexpressing and knockout mouse chromaffin cells, carbon fibre amperometry, Ca2+ entry measurements, readily releasable pool size assay, acute calcineurin inhibitor comparison Human molecular genetics Medium 18180251
2012 RCAN1-1L induction causes dramatic degradation of mitochondria (mitophagy) involving the adenine nucleotide translocator and mitochondrial permeability transition pore opening, and shifts cellular bioenergetics from aerobic respiration to glycolysis. Inducible RCAN1-1L expression in neuronal cells, mitochondrial mass/morphology analysis, ANT and mPTP involvement assays, cellular bioenergetics measurement (oxygen consumption vs glycolysis) The Journal of biological chemistry Medium 22389495
2015 RCAN1 (triplicated in Down syndrome) inhibits TrkA receptor endocytosis downstream of calcineurin phosphatase, impairing NGF-dependent neurotrophin trafficking, neuronal survival, and sympathetic innervation. Genetically correcting RCAN1 levels in Down syndrome mice restored NGF-dependent receptor trafficking and neuronal survival. Down syndrome mouse model, RCAN1 genetic correction, TrkA receptor internalization assay, retrograde NGF trafficking assay, sympathetic innervation quantification, neuronal survival assay Nature communications High 26658127
2018 RCAN1 maintains a more fused mitochondrial network by inhibiting calcineurin-dependent activation of the fission protein DRP1. When RCAN1 is depleted, calcineurin activates DRP1, leading to mitochondrial fragmentation, reduced membrane potential, reduced O2 consumption, and impaired mitochondrial Ca2+ buffering. Pharmacological inhibition of calcineurin, DRP1, or calpains (CAPN) restored protection in RCAN1-depleted cardiomyocytes. RCAN1 KO cardiomyocytes, adenoviral RCAN1 overexpression, DRP1 phosphorylation assay, mitochondrial morphology imaging, pharmacological inhibitors (calcineurin, DRP1, calpain), Down syndrome iPSC disomic/trisomic comparison Circulation research High 29362227
2012 RCAN1 (DSCR1) interacts with FMRP and regulates dendritic spine morphogenesis and local protein synthesis. Decreasing FMRP levels restores DSCR1-induced changes in dendritic spine morphology. Co-immunoprecipitation of DSCR1 and FMRP, dendritic spine morphology analysis, local protein synthesis assay, FMRP knockdown rescue experiment The EMBO journal Medium 22863780
2016 RCAN1 (DSCR1) controls axon outgrowth by modulating growth cone actin dynamics through regulation of cofilin phosphorylation/dephosphorylation. RCAN1 also mediates BDNF-induced local protein synthesis and growth cone turning. DSCR1 loss-of-function in neurons, phospho-cofilin/cofilin ratio measurement, live-imaging of axon outgrowth, BDNF-induced growth cone turning assay, local protein synthesis assay The Journal of cell biology Medium 27185837
2019 RCAN1 binds to TET1 introns and regulates TET1 splicing, thereby modulating TET1 protein levels. TET1 controls demethylation of the miR-124 promoter to regulate miR-124 expression, which in turn controls adult hippocampal neurogenesis. Correcting TET1 levels in RCAN1 KO mice prevents defective adult neurogenesis. RCAN1 KO mice, RNA-binding/splicing assay (RCAN1-TET1 interaction), miR-124 promoter methylation analysis, adult neurogenesis quantification, genetic rescue (TET1 correction in RCAN1 KO), Down syndrome mouse model rescue The EMBO journal Medium 31304631
2011 RCAN1 GSK3β nuclear export switches RCAN1 from a calcineurin inhibitor to a facilitator of calcineurin-NFAT signaling in a dose-dependent manner. PI3K signaling promotes GSK3β nuclear export, enabling the facilitatory role. Sequential phosphorylation of RCAN1 mediates this switch. Single-cell experimentation, mathematical modeling, PI3K inhibitor treatment, GSK3β nuclear export assay, NFAT reporter assay, dose-response analysis Journal of cell science Medium 21172821
2005 Raf-1 is a direct binding partner of DSCR1. Two Raf-1 binding regions were identified in DSCR1 (N-terminus and C-terminus). Calpain cleaves DSCR1 and generates fragments with differential binding affinity to Raf-1 versus calcineurin. Pulldown assay with DSCR1 as bait, co-immunoprecipitation in GFP-DSCR1 expressing cells, deletion mapping of binding regions, calpain cleavage assay Archives of biochemistry and biophysics Medium 15935327
2012 RCAN1-1L promotes CREB phosphorylation and cAMP response element-mediated gene transcription. This effect is dependent on RCAN1's ability to inhibit calcineurin. RCAN1 induces Bcl-2 expression via CREB activation, protecting neurons from H2O2-induced apoptosis. RCAN1 inhibits H2O2-induced MAPK and AP-1 activation. RCAN1 overexpression and shRNA knockdown in neuronal cells, CREB phosphorylation western blot, CRE-luciferase reporter assay, Bcl-2 expression analysis, H2O2 cytotoxicity assay, calcineurin inhibitor comparison The Journal of biological chemistry / Journal of cellular biochemistry Medium 21890628 23150431
2008 CREB activates proteasomal degradation of RCAN1 via the ubiquitin-proteasome pathway. CREB-enhanced ubiquitination of RCAN1 increases its turnover rate. This regulatory function depends on CREB's transcriptional activation. Proteasome inhibitor treatment, ubiquitination assay, RCAN1 protein turnover (pulse-chase), CREB overexpression and transcriptional activation mutants FEBS letters Medium 18485898
2008 Oxidative stress (H2O2) induces ubiquitination of RCAN1 mediated by SCFβ-TrCP ubiquitin ligase. β-TrCP interacts with RCAN1 in an H2O2-dependent manner. In vitro ubiquitination assay showed SCFβ-TrCP (but not SCFFBW4) ubiquitinates RCAN1 in response to H2O2. Knockdown of β-TrCP abolished H2O2-induced RCAN1 decrease in cells and primary neurons. Co-immunoprecipitation of β-TrCP and FBW4 with RCAN1, in vitro ubiquitination assay, siRNA knockdown of β-TrCP, primary hippocampal and cortical neuron experiments International journal of molecular medicine Medium 18575781
2012 NEDD8 is covalently conjugated to RCAN1-1S at lysine residues K96, K104, and K107. Neddylation enhances RCAN1 protein stability by inhibiting proteasomal degradation, increases RCAN1 binding to calcineurin, and potentiates its inhibitory activity toward downstream NFAT signaling. NEDD8 conjugation mapping to K96/K104/K107 by mutagenesis, protein stability assay, Co-immunoprecipitation of neddylated RCAN1 with calcineurin, NFAT reporter assay, proteasome inhibitor comparison PloS one Medium 23118980
2003 Oxidative stress (H2O2, peroxynitrite, menadione) induces hyperphosphorylation of DSCR1/RCAN1 protein. Phosphorylation of serines in a 13-amino acid calcineurin-interacting conserved region of DSCR1 attenuates its inhibition of calcineurin. H2O2 and oxidant treatment of human cells, gel mobility shift analysis, kinase inhibitor panel, phosphopeptide synthesis and calcineurin inhibition assay Free radical biology & medicine Medium 12927602
2002 DSCR1/RCAN1 protein localizes preferentially to the nucleus, independently of isoform, cell line, or GFP orientation. A C-terminal segment is important for nuclear localization. Site-directed mutagenesis indicates serine and threonine residues contribute to nuclear targeting, suggesting phosphorylation regulates localization. GFP fusion protein imaging in multiple cell lines, deletion mutagenesis, site-directed mutagenesis of serine/threonine residues BMC cell biology Low 12225619
2011 In Drosophila, the RCAN1 ortholog sarah (sra) is required for normal sleep. Sleep reduction in sra mutants correlates with decreased Sra protein levels. Pan-neural sra expression rescues the sleep phenotype. Calcineurin (CanA-14F and CanB subunits) loss also reduces sleep, and sra sleep defects are suppressed by calcineurin mutations, establishing that sra and calcineurin affect sleep through a common mechanism. Drosophila sra mutants, calcineurin subunit knockout mutants, pan-neural transgenic rescue, constitutively active calcineurin expression, epistasis analysis The Journal of neuroscience High 21900555
2013 Increased dosage of DSCR1 and DYRK1A in neocortical progenitor cells cooperatively suppresses NFATc activity, delaying neuronal differentiation and altering laminar fate in the developing neocortex. Counteracting the dysregulated pathway ameliorates delayed neuronal differentiation in the Ts1Cje Down syndrome mouse model. In utero electroporation for DYRK1A and DSCR1 overexpression in neocortex, Ts1Cje DS mouse model, NFATc activity assay, neuronal differentiation and laminar fate analysis, pathway rescue Genes & development High 24352425
2016 RCAN1 overexpression in β-cells causes mitochondrial dysfunction including hyperpolarized membrane potential, reduced oxidative phosphorylation, and low ATP production. This impairs both glucose-stimulated membrane depolarization and ATP-dependent insulin granule exocytosis, causing hypoinsulinemia. RCAN1-overexpressing mice, in vivo glucose-stimulated insulin secretion test, β-cell mitochondrial membrane potential measurement, oxidative phosphorylation assay, ATP production measurement, insulin granule exocytosis assay PLoS genetics Medium 27195491
2010 VEGF induces RCAN1.4 expression in endothelial cells via Ca2+/calcineurin and protein kinase C-delta (PKC-δ) pathways. siRNA knockdown of RCAN1.4 results in decreased cell migration and disrupted tubular morphogenesis. RCAN1.4 knockdown increases NFAT-regulated gene expression, confirming a negative feedback role on calcineurin-NFAT signaling. PKC and calcineurin inhibitors, siRNA silencing of PKC-δ and RCAN1.4, RCAN1.4 promoter assay, NFAT target gene expression, endothelial cell migration assay, collagen gel tubulogenesis assay PloS one Medium 20625401
2017 RCAN1.4 regulates VEGFR-2 internalization (agonist-stimulated receptor endocytosis) and establishment of endothelial cell polarity in response to VEGF. RCAN1.4 is required for efficient VEGF-mediated cytoskeletal reorganization, directed cell migration, and sprouting angiogenesis. Morpholino silencing of zebrafish RCAN1.4 orthologue disrupted vascular development in vivo. siRNA-mediated knockdown, adenoviral RCAN1.4 overexpression, VEGFR-2 internalization assay, cell polarity assay, cytoskeletal imaging, directed cell migration, sprouting assay, zebrafish morpholino knockdown Angiogenesis Medium 28271280
2009 RCAN1 (Rcan1) negatively regulates FcεRI-mediated mast cell activation. Rcan1-deficient mast cells show increased calcineurin activity, increased NFAT and NF-κB activation, and increased cytokine production and degranulation. Egr1 transcription factor controls Rcan1 expression through a functional Egr1 binding site in the RCAN1 promoter. Forced expression of Rcan1 in Rcan1-deficient mast cells reduced cytokine production. Rcan1 KO mast cells, calcineurin activity assay, NFAT and NF-κB reporter assays, cytokine ELISA, passive cutaneous anaphylaxis in vivo, Egr1 promoter analysis, ChIP, Rcan1 reconstitution in KO cells The Journal of experimental medicine High 19124655
2013 RCAN1 deficiency reduces atherosclerosis severity in Apoe−/− mice. Rcan1 regulates CD36 expression in macrophages, and its inactivation reduces oxLDL uptake, resistance to oxLDL-mediated inhibition of macrophage migration, and increases anti-inflammatory markers. Bone marrow transplantation of Apoe−/−Rcan1−/− cells into Apoe−/− recipients confers atherosclerosis resistance, demonstrating the effect is hematopoietic cell-autonomous. Apoe−/−Rcan1−/− double-knockout mice, bone marrow transplantation, CD36 expression assay, oxLDL uptake assay, macrophage migration assay, atherosclerosis lesion quantification EMBO molecular medicine Medium 24127415
2015 RCAN1 overexpression promotes DRP1-mediated mitochondrial fission and age-dependent tau pathology. Brain-specific overexpression of human RCAN1.1S induces memory and synaptic plasticity deficits, tau pathology, and dysregulation of DRP1 activity associated with mitochondrial dysfunction and oxidative stress. Brain-specific RCAN1.1S transgenic mice, DRP1 activity assay, mitochondrial morphology analysis, behavioral testing, synaptic plasticity electrophysiology, tau pathology immunostaining Acta neuropathologica Medium 26497675
2023 RCAN1 knockdown rescues Huntington's disease patient-derived striatal neurons (MSNs) from degeneration by enhancing calcineurin activity, leading to TFEB nuclear localization through dephosphorylation and activation of autophagy/longevity gene chromatin accessibility. A glibenclamide analog (G2-115) reduces RCAN1-calcineurin interaction, phenocopying RCAN1 knockdown. Direct neuronal reprogramming of human fibroblasts to MSNs, longitudinal transcriptomics, RCAN1 knockdown (siRNA/shRNA), calcineurin activity assay, TFEB nuclear localization assay, chromatin accessibility (ATAC-seq), pharmacological G2-115 treatment Nature aging High 38066314
2017 LRRK2 kinase phosphorylates RCAN1-1S and is upregulated during IL-1β treatment. LRRK2-mediated phosphorylation of RCAN1 promotes formation of Tollip-RCAN1 protein complexes, decreases Tollip-IRAK1 interaction, increases IRAK1-TRAF6 complex formation, enhances TAK1 activity, and promotes NF-κB transcriptional activity and IL-8 production. In vitro kinase assay, co-immunoprecipitation, NF-κB reporter assay, IL-8 ELISA, LRRK2 and RCAN1 overexpression/knockdown Frontiers in cellular neuroscience Medium 28553204
2010 C/EBPβ directly binds to multiple conserved sites in the RCAN1-4 promoter and cooperates with NFAT to regulate RCAN1-4 expression. A direct protein-protein interaction between C/EBPβ and NFAT was demonstrated, and complex formation occurs at NFAT-C/EBPβ composite sites. Depletion of C/EBPβ decreased maximal RCAN1-4 activation by calcineurin. C/EBPβ occupancy of Rcan1-4 promoter increased in mouse models of heart failure. EMSA (electrophoretic mobility shift assay), chromatin immunoprecipitation (ChIP), co-immunoprecipitation of C/EBPβ and NFAT, RCAN1-4 luciferase reporter, C/EBPβ depletion, heart failure mouse model The Journal of biological chemistry Medium 20371871
2019 RCAN1.4 expression is epigenetically suppressed by DNA methylation mediated by DNMT1 and DNMT3b, as shown by ChIP assay. RCAN1.4 overexpression alleviates liver fibrosis by inhibiting CaN/NFAT3 signaling. Knockdown of RCAN1.4 exacerbates TGF-β1-induced liver fibrosis in a CaN/NFAT3-dependent manner. Bisulfite sequencing PCR, ChIP assay with DNMT1/DNMT3b, 5-azadC demethylation, rAAV8-RCAN1.4 in vivo delivery, CaN/NFAT3 reporter and activity assay, liver fibrosis mouse model Theranostics Medium 31285763

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2006 NFAT dysregulation by increased dosage of DSCR1 and DYRK1A on chromosome 21. Nature 534 16554754
2000 DSCR1, overexpressed in Down syndrome, is an inhibitor of calcineurin-mediated signaling pathways. Human molecular genetics 398 10861295
2009 Down's syndrome suppression of tumour growth and the role of the calcineurin inhibitor DSCR1. Nature 286 19458618
2001 Chronic overexpression of the calcineurin inhibitory gene DSCR1 (Adapt78) is associated with Alzheimer's disease. The Journal of biological chemistry 177 11483593
1997 Genomic organization, alternative splicing, and expression patterns of the DSCR1 (Down syndrome candidate region 1) gene. Genomics 165 9325060
2006 Phosphorylation inhibits turnover of the tau protein by the proteasome: influence of RCAN1 and oxidative stress. The Biochemical journal 148 16939415
2004 Down syndrome critical region protein 1 (DSCR1), a novel VEGF target gene that regulates expression of inflammatory markers on activated endothelial cells. Blood 139 15016650
2009 Interaction between TAK1-TAB1-TAB2 and RCAN1-calcineurin defines a signalling nodal control point. Nature cell biology 113 19136967
2016 Alpha-2 macroglobulin in Alzheimer's disease: a marker of neuronal injury through the RCAN1 pathway. Molecular psychiatry 112 27872486
2008 Targeted deletion of the calcineurin inhibitor DSCR1 suppresses tumor growth. Cancer cell 111 18455125
2002 The DSCR1 (Adapt78) isoform 1 protein calcipressin 1 inhibits calcineurin and protects against acute calcium-mediated stress damage, including transient oxidative stress. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 111 12039863
2011 Amyloid-β toxicity and tau hyperphosphorylation are linked via RCAN1 in Alzheimer's disease. Journal of Alzheimer's disease : JAD 109 21876249
2009 Degradation of regulator of calcineurin 1 (RCAN1) is mediated by both chaperone-mediated autophagy and ubiquitin proteasome pathways. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 101 19509306
2011 Regulator of calcineurin 1 (RCAN1) facilitates neuronal apoptosis through caspase-3 activation. The Journal of biological chemistry 97 21216952
2005 Identification of a peptide fragment of DSCR1 that competitively inhibits calcineurin activity in vitro and in vivo. Proceedings of the National Academy of Sciences of the United States of America 97 16131541
2007 The Down syndrome critical region protein RCAN1 regulates long-term potentiation and memory via inhibition of phosphatase signaling. The Journal of neuroscience : the official journal of the Society for Neuroscience 92 18045910
2020 Tumor-derived exosomal miR-619-5p promotes tumor angiogenesis and metastasis through the inhibition of RCAN1.4. Cancer letters 91 32004570
2005 Multiple roles of the DSCR1 (Adapt78 or RCAN1) gene and its protein product calcipressin 1 (or RCAN1) in disease. Cellular and molecular life sciences : CMLS 90 16231093
2008 Coordination of growth and endoplasmic reticulum stress signaling by regulator of calcineurin 1 (RCAN1), a novel ATF6-inducible gene. The Journal of biological chemistry 87 18319259
2007 RCAN1 (DSCR1) increases neuronal susceptibility to oxidative stress: a potential pathogenic process in neurodegeneration. Human molecular genetics 74 17341486
2012 Over-expression of RCAN1 causes Down syndrome-like hippocampal deficits that alter learning and memory. Human molecular genetics 70 22511596
2008 DSCR1/RCAN1 regulates vesicle exocytosis and fusion pore kinetics: implications for Down syndrome and Alzheimer's disease. Human molecular genetics 69 18180251
2011 Regulation of RCAN1 protein activity by Dyrk1A protein-mediated phosphorylation. The Journal of biological chemistry 68 21965663
2009 Two key genes closely implicated with the neuropathological characteristics in Down syndrome: DYRK1A and RCAN1. BMB reports 67 19192387
2000 A new gene family including DSCR1 (Down Syndrome Candidate Region 1) and ZAKI-4: characterization from yeast to human and identification of DSCR1-like 2, a novel human member (DSCR1L2). Genomics 67 10756093
2007 RCAN1-1L is overexpressed in neurons of Alzheimer's disease patients. The FEBS journal 66 17331188
2012 Regulation of RCAN1 translation and its role in oxidative stress-induced apoptosis. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 63 23038757
2003 Oxidative and calcium stress regulate DSCR1 (Adapt78/MCIP1) protein. Free radical biology & medicine 63 12927602
2015 RCAN1 overexpression promotes age-dependent mitochondrial dysregulation related to neurodegeneration in Alzheimer's disease. Acta neuropathologica 60 26497675
2012 Chronic expression of RCAN1-1L protein induces mitochondrial autophagy and metabolic shift from oxidative phosphorylation to glycolysis in neuronal cells. The Journal of biological chemistry 59 22389495
2017 RCAN1.4 regulates VEGFR-2 internalisation, cell polarity and migration in human microvascular endothelial cells. Angiogenesis 57 28271280
2001 Dscr1, a novel endogenous inhibitor of calcineurin signaling, is expressed in the primitive ventricle of the heart and during neurogenesis. Mechanisms of development 57 11231093
2020 Disruption of super-enhancer-driven tumor suppressor gene RCAN1.4 expression promotes the malignancy of breast carcinoma. Molecular cancer 56 32771023
2006 Alzheimer's disease and endocytic dysfunction: clues from the Down syndrome-related proteins, DSCR1 and ITSN1. Ageing research reviews 56 16442855
2008 Calcium/calcineurin signaling in primary cortical astrocyte cultures: Rcan1-4 and cyclooxygenase-2 as NFAT target genes. Glia 55 18293408
2006 RCAN1 (DSCR1 or Adapt78) stimulates expression of GSK-3beta. The FEBS journal 53 16649988
2012 Regulator of calcineurin 1 (Rcan1) has a protective role in brain ischemia/reperfusion injury. Journal of neuroinflammation 52 22397398
2018 Down Syndrome Critical Region 1 Gene, Rcan1, Helps Maintain a More Fused Mitochondrial Network. Circulation research 50 29362227
2012 Kaposi's sarcoma herpesvirus K15 protein contributes to virus-induced angiogenesis by recruiting PLCγ1 and activating NFAT1-dependent RCAN1 expression. PLoS pathogens 50 23028325
2017 RCAN1-4 is a thyroid cancer growth and metastasis suppressor. JCI insight 49 28289712
2019 Methylation of RCAN1.4 mediated by DNMT1 and DNMT3b enhances hepatic stellate cell activation and liver fibrogenesis through Calcineurin/NFAT3 signaling. Theranostics 48 31285763
2011 Calcineurin and its regulator sra/DSCR1 are essential for sleep in Drosophila. The Journal of neuroscience : the official journal of the Society for Neuroscience 46 21900555
2012 DSCR1 interacts with FMRP and is required for spine morphogenesis and local protein synthesis. The EMBO journal 45 22863780
2016 A Syntenic Cross Species Aneuploidy Genetic Screen Links RCAN1 Expression to β-Cell Mitochondrial Dysfunction in Type 2 Diabetes. PLoS genetics 43 27195491
2015 RCAN1 links impaired neurotrophin trafficking to aberrant development of the sympathetic nervous system in Down syndrome. Nature communications 43 26658127
2013 Increased dosage of DYRK1A and DSCR1 delays neuronal differentiation in neocortical progenitor cells. Genes & development 43 24352425
2014 RCAN1 overexpression exacerbates calcium overloading-induced neuronal apoptosis. PloS one 41 24751678
2012 Increased expression of the glucose-responsive gene, RCAN1, causes hypoinsulinemia, β-cell dysfunction, and diabetes. Endocrinology 41 23011918
2011 A hidden incoherent switch regulates RCAN1 in the calcineurin-NFAT signaling network. Journal of cell science 41 21172821
2014 Calcineurin and its regulator, RCAN1, confer time-of-day changes in susceptibility of the heart to ischemia/reperfusion. Journal of molecular and cellular cardiology 40 24838101
2010 VEGF stimulates RCAN1.4 expression in endothelial cells via a pathway requiring Ca2+/calcineurin and protein kinase C-delta. PloS one 40 20625401
2004 Aggregate formation and synaptic abnormality induced by DSCR1. Journal of neurochemistry 40 15009650
2018 RCAN1 is a marker of oxidative stress, induced in acute pancreatitis. Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.] 39 30139658
2011 Do RCAN1 proteins link chronic stress with neurodegeneration? FASEB journal : official publication of the Federation of American Societies for Experimental Biology 39 21680892
2013 A major role for RCAN1 in atherosclerosis progression. EMBO molecular medicine 38 24127415
2014 Calcineurin-NFAT activation and DSCR-1 auto-inhibitory loop: how is homoeostasis regulated? Journal of biochemistry 37 24505143
2020 Genome-wide mRNA profiling identifies RCAN1 and GADD45A as regulators of the transitional switch from survival to apoptosis during ER stress. The FEBS journal 36 31880863
2009 Regulator of calcineurin (RCAN1-1L) is deficient in Huntington disease and protective against mutant huntingtin toxicity in vitro. The Journal of biological chemistry 36 19270310
2013 Chronic high levels of the RCAN1-1 protein may promote neurodegeneration and Alzheimer disease. Free radical biology & medicine 35 23369757
2011 Behavioral characterization of a mouse model overexpressing DSCR1/ RCAN1. PloS one 34 21364922
2014 Aberrant expression of RCAN1 in Alzheimer's pathogenesis: a new molecular mechanism and a novel drug target. Molecular neurobiology 32 24752590
2014 Overexpression of Rcan1-1L inhibits hypoxia-induced cell apoptosis through induction of mitophagy. Molecules and cells 32 25377251
2010 The CCAAT/enhancer binding protein beta (C/EBPbeta) cooperates with NFAT to control expression of the calcineurin regulatory protein RCAN1-4. The Journal of biological chemistry 32 20371871
2013 Nebula/DSCR1 upregulation delays neurodegeneration and protects against APP-induced axonal transport defects by restoring calcineurin and GSK-3β signaling. PLoS genetics 31 24086147
2017 The neuronal and endocrine roles of RCAN1 in health and disease. Clinical and experimental pharmacology & physiology 30 29094385
2004 DSCR1(Adapt78) modulates expression of SOD1. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 30 14718387
2015 The RCAN1 inhibits NF-κB and suppresses lymphoma growth in mice. Cell death & disease 29 26492364
2009 Integrative genomics identifies DSCR1 (RCAN1) as a novel NFAT-dependent mediator of phenotypic modulation in vascular smooth muscle cells. Human molecular genetics 29 19926569
2018 Epigenetic regulation of RCAN1 expression in kidney disease and its role in podocyte injury. Kidney international 28 30366682
2008 Upregulation of DSCR1 (RCAN1 or Adapt78) in the peri-infarct cortex after experimental stroke. Experimental neurology 28 18485347
2008 c-Jun inhibits thapsigargin-induced ER stress through up-regulation of DSCR1/Adapt78. Experimental biology and medicine (Maywood, N.J.) 27 18641051
2020 Inhibition of miR-103a-3p suppresses the proliferation in oral squamous cell carcinoma cells via targeting RCAN1. Neoplasma 26 32122140
2016 DSCR1 is required for both axonal growth cone extension and steering. The Journal of cell biology 26 27185837
2005 Raf-1 is a binding partner of DSCR1. Archives of biochemistry and biophysics 26 15935327
2014 RCAN1 regulates mitochondrial function and increases susceptibility to oxidative stress in mammalian cells. Oxidative medicine and cellular longevity 25 25009690
2009 Rcan1 negatively regulates Fc epsilonRI-mediated signaling and mast cell function. The Journal of experimental medicine 24 19124655
2000 The murine DSCR1-like (Down syndrome candidate region 1) gene family: conserved synteny with the human orthologous genes. Gene 24 11080588
2013 A single extra copy of Dscr1 improves survival of mice developing spontaneous lung tumors through suppression of tumor angiogenesis. Cancer letters 23 24051307
2007 Brain expression of the calcineurin inhibitor RCAN1 (Adapt78). Archives of biochemistry and biophysics 22 17910944
2009 Glucocorticoid evoked upregulation of RCAN1-1 in human leukemic CEM cells susceptible to apoptosis. Journal of molecular signaling 21 19725972
2002 Mutational analyses of the signals involved in the subcellular location of DSCR1. BMC cell biology 21 12225619
2024 Suppression of RCAN1 alleviated lipid accumulation and mitochondrial fission in diabetic cardiomyopathy. Metabolism: clinical and experimental 20 39053690
2018 RCAN1.4 acts as a suppressor of cancer progression and sunitinib resistance in clear cell renal cell carcinoma. Experimental cell research 20 30267660
2017 Leucine-Rich Repeat Kinase 2 (LRRK2) Stimulates IL-1β-Mediated Inflammatory Signaling through Phosphorylation of RCAN1. Frontiers in cellular neuroscience 20 28553204
2011 The regulator of calcineurin 1 (RCAN1/DSCR1) activates the cAMP response element-binding protein (CREB) pathway. The Journal of biological chemistry 20 21890628
2008 CREB activates proteasomal degradation of DSCR1/RCAN1. FEBS letters 20 18485898
2007 Overexpression of DSCR1 blocks zinc-induced neuronal cell death through the formation of nuclear aggregates. Molecular and cellular neurosciences 20 17596961
2019 DSCR1-mediated TET1 splicing regulates miR-124 expression to control adult hippocampal neurogenesis. The EMBO journal 19 31304631
2017 Pyrrolidine dithiocarbamate (PDTC) inhibits inflammatory signaling via expression of regulator of calcineurin activity 1 (RCAN1): Anti-inflammatory mechanism of PDTC through RCAN1 induction. Biochemical pharmacology 19 28712932
2011 Regulator of Calcineurin 1 Isoform 4 (RCAN1.4) Is Overexpressed in the Glomeruli of Diabetic Mice. The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology 19 22128263
2022 RCAN1 deficiency aggravates sepsis-induced cardiac remodeling and dysfunction by accelerating mitochondrial pathological fission. Inflammation research : official journal of the European Histamine Research Society ... [et al.] 18 36305917
2012 Covalent NEDD8 conjugation increases RCAN1 protein stability and potentiates its inhibitory action on calcineurin. PloS one 18 23118980
2007 Down syndrome candidate region 1-like 1 (DSCR1-L1) mimics the inhibitory effects of DSCR1 on calcineurin signaling in endothelial cells and inhibits angiogenesis. The Journal of surgical research 18 17610901
2003 DSCR1(Adapt78)--a Janus gene providing stress protection but causing Alzheimer's disease? IUBMB life 18 12716059
2023 Longitudinal modeling of human neuronal aging reveals the contribution of the RCAN1-TFEB pathway to Huntington's disease neurodegeneration. Nature aging 17 38066314
2013 NGF upregulates the plasminogen activation inhibitor-1 in neurons via the calcineurin/NFAT pathway and the Down syndrome-related proteins DYRK1A and RCAN1 attenuate this effect. PloS one 17 23825664
2013 Calcineurin-Rcan1 interaction contributes to stem cell factor-mediated mast cell activation. Journal of immunology (Baltimore, Md. : 1950) 17 24218457
2008 Oxidative stress-induced ubiquitination of RCAN1 mediated by SCFbeta-TrCP ubiquitin ligase. International journal of molecular medicine 17 18575781
2005 Restoration of DSCR1 to disomy in the trisomy 16 mouse model of Down syndrome does not correct cardiac or craniofacial development anomalies. Developmental dynamics : an official publication of the American Association of Anatomists 17 15906378
2013 CREB-mediated Bcl-2 expression contributes to RCAN1 protection from hydrogen peroxide-induced neuronal death. Journal of cellular biochemistry 16 23150431

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