Affinage

ARC

Activity-regulated cytoskeleton-associated protein · UniProt Q7LC44

Length
396 aa
Mass
45.3 kDa
Annotated
2026-04-28
100 papers in source corpus 24 papers cited in narrative 24 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

Arc is an activity-regulated immediate early gene product that serves as a master organizer of synaptic plasticity, coupling neuronal activity to bidirectional changes in synaptic strength through distinct cytoplasmic and nuclear mechanisms. In the cytoplasm, Arc promotes clathrin-mediated endocytosis of AMPA receptors by interacting with endophilin, dynamin, and AP-2, thereby mediating mGluR-dependent LTD and homeostatic scaling, while its accumulation at inactive synapses via CaMKIIβ binding enables synapse-specific receptor removal (PMID:19005037, PMID:18614031, PMID:22579289, PMID:28890421). Arc also stabilizes F-actin through sustained synthesis-dependent cofilin phosphorylation, which is required for LTP consolidation, and translocates to the nucleus where it increases PML nuclear bodies to repress GluA1 transcription and associates with active chromatin marks to broadly regulate gene expression (PMID:17898216, PMID:23749147, PMID:36009494). Arc protein levels are tightly controlled by Ube3A- and Triad3A/RNF216-mediated ubiquitin-proteasomal degradation, GSK3β-dependent phosphorylation, and lysine acetylation, with the temporal profile of Arc expression dictating the direction and magnitude of plasticity and cognitive flexibility (PMID:20211139, PMID:24945773, PMID:29861284, PMID:29162813).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 2003 Medium

    Establishing that Arc translation at synapses is regulated by extracellular signals through a defined signaling pathway resolved how local Arc protein supply is controlled: Reelin stimulates Arc synthesis via integrin receptors and mTOR.

    Evidence Radiolabeled amino acid incorporation in synaptoneurosomes with rapamycin and echistatin pharmacology

    PMID:12707415

    Open questions at the time
    • Whether Reelin-integrin-mTOR axis operates in vivo at synapses during plasticity
    • Relative contribution versus other translation-control pathways (e.g., BDNF-ERK)
  2. 2007 High

    Demonstrating that sustained Arc synthesis is required for F-actin stabilization and LTP consolidation in vivo established Arc as a necessary effector of long-lasting synaptic potentiation, not only depression.

    Evidence In vivo antisense infusion in dentate gyrus at multiple time points with F-actin staining, cofilin phosphorylation, and electrophysiology

    PMID:17898216

    Open questions at the time
    • Direct molecular target through which Arc stabilizes F-actin or promotes cofilin phosphorylation
    • Whether Arc acts on actin through a direct or indirect mechanism
  3. 2008 High

    Identifying Arc's physical interaction with endophilin and dynamin and its requirement for AMPAR endocytosis during mGluR-LTD established the core cytoplasmic mechanism by which Arc weakens synapses.

    Evidence Co-immunoprecipitation, receptor trafficking assays, antisense knockdown with electrophysiology in hippocampal neurons

    PMID:18614031 PMID:19005037

    Open questions at the time
    • How Arc is selectively recruited to specific AMPAR-containing endocytic pits
    • Whether Arc has direct membrane-deforming activity independent of endophilin/dynamin
  4. 2008 High

    Mapping the SARE enhancer element with CREB, MEF2, and SRF binding sites explained how diverse neuronal activity patterns converge on rapid Arc transcription.

    Evidence Luciferase reporter assays in cortical neurons with binding-site deletion/mutation

    PMID:19116276

    Open questions at the time
    • How chromatin state at the SARE locus is dynamically regulated
    • Whether additional distal enhancers contribute
  5. 2010 High

    Discovering that Ube3A ubiquitinates Arc to control its degradation linked Arc turnover to Angelman syndrome pathology and explained how excessive Arc accumulation reduces synaptic AMPAR levels.

    Evidence Biochemical ubiquitination assays, neuronal knockdown/KO with surface AMPAR quantification

    PMID:20211139

    Open questions at the time
    • Which specific lysine residues are targeted by Ube3A
    • Relative contribution of Ube3A versus other E3 ligases in different brain regions
  6. 2010 High

    Linking Arc's AMPAR endocytosis function to dendritic spine morphology and network excitability showed that Arc shapes structural plasticity and prevents epileptic-like activity.

    Evidence Arc overexpression/KO with spine morphology analysis, surface GluA1 internalization, in vivo EEG

    PMID:20921410

    Open questions at the time
    • Whether spine thinning is a direct structural consequence of AMPAR removal or involves additional signaling
  7. 2012 High

    Revealing that Arc accumulates at inactive synapses via CaMKIIβ-dependent 'inverse synaptic tagging' explained how a globally induced protein achieves synapse-specific receptor removal during homeostatic scaling.

    Evidence Co-immunoprecipitation, live Arc-GFP imaging, CaMKIIβ KO mice, single-synapse surface GluA1 quantification

    PMID:22579289

    Open questions at the time
    • How CaMKIIβ-Arc interaction is terminated at reactivated synapses
    • Whether other synaptic tags cooperate with CaMKIIβ
  8. 2013 High

    Demonstrating that nuclear Arc increases PML bodies and represses GluA1 transcription revealed a second, transcription-level mechanism by which Arc downregulates synaptic strength during homeostatic plasticity.

    Evidence Subcellular fractionation, domain mutants, GluA1 transcription assays, electrophysiology

    PMID:23749147

    Open questions at the time
    • How Arc promotes PML body assembly mechanistically
    • Whether nuclear Arc regulates genes beyond GluA1
  9. 2014 High

    Identification of Triad3A/RNF216 as a second E3 ligase that ubiquitinates Arc at endocytic sites established that multiple degradation pathways independently control Arc protein lifetime at distinct subcellular locations.

    Evidence Co-immunoprecipitation, ubiquitination assay, Triad3A knockdown with AMPAR surface quantification and electrophysiology

    PMID:24945773

    Open questions at the time
    • Whether Ube3A and Triad3A target overlapping or distinct lysine residues
    • Temporal ordering of the two E3 ligase activities during plasticity
  10. 2015 High

    Solving the crystal structure of Arc revealed a retrotransposon-derived bi-lobar capsid-like fold with a hydrophobic pocket that mediates binding to TARPγ2/Stargazin and CaMKII, providing the first atomic-level understanding of Arc's protein interaction mode.

    Evidence X-ray crystallography, co-crystal structures with peptide ligands, pocket mutagenesis

    PMID:25864631

    Open questions at the time
    • Full-length Arc structure including the disordered linker region
    • Whether the capsid-like fold enables higher-order Arc assemblies in vivo
  11. 2015 Medium

    Activity-dependent recruitment of a PHF8-TIP60 chromatin-modifying complex to the Arc promoter to remove H3K9me2 and install H3K9acS10P clarified how epigenetic remodeling permits rapid Arc transcription.

    Evidence ChIP, gain/loss-of-function of PHF8 and TIP60 in hippocampal neurons

    PMID:26464965

    Open questions at the time
    • Single lab; awaits independent replication
    • Whether PHF8-TIP60 recruitment is specific to Arc or shared across IEGs
  12. 2017 Medium

    GSK3β-mediated phosphorylation was shown to promote Arc degradation, adding a kinase-dependent layer to Arc turnover control and linking it to spine structural remodeling.

    Evidence In vitro kinase assay, mass spectrometry phosphosite mapping, Arc mutant overexpression with spine morphology analysis

    PMID:28670266

    Open questions at the time
    • Identity of the phosphatase that reverses GSK3β phosphorylation on Arc
    • In vivo validation of GSK3-dependent Arc degradation during plasticity
  13. 2017 Medium

    Identification of lysine acetylation as a stability-regulating post-translational modification of Arc expanded the repertoire of Arc protein-level regulatory mechanisms beyond ubiquitination and phosphorylation.

    Evidence Chemogenomic screen, mass spectrometry acetylation site identification in cortical neurons

    PMID:29162813

    Open questions at the time
    • Identity of the acetyltransferase(s) and deacetylase(s) acting on Arc in vivo
    • Functional consequence of specific acetylation sites on Arc interactions
  14. 2018 High

    ArcKR knockin mice with mutated ubiquitination sites proved that the temporal precision of Arc degradation determines the threshold and magnitude of mGluR-LTD and is required for cognitive flexibility.

    Evidence Knockin mice, Arc protein decay assays, mGluR-LTD electrophysiology, reversal learning behavioral tests

    PMID:29861284

    Open questions at the time
    • Which E3 ligase(s) are primarily responsible for ubiquitination of the mutated sites
    • Whether prolonged Arc also affects LTP consolidation in these mice
  15. 2021 Medium

    Demonstrating that Arc is locally translated in peripheral sensory fibers and that Arc-containing extracellular vesicles rescue neurogenic inflammation in Arc KO mice extended Arc function beyond the CNS.

    Evidence Ribosome profiling, Arc KO mice, EV injection rescue, infrared thermometry

    PMID:34326146

    Open questions at the time
    • Mechanism by which Arc-EVs modulate vascular tone
    • Whether peripheral Arc capsid-like assemblies mirror CNS structures
  16. 2022 Medium

    ChIP and transcriptomic profiling revealed that nuclear Arc associates with active enhancer histone marks (H3K27Ac, H3K9Ac) and broadly regulates over 1900 genes, vastly expanding its nuclear role beyond GluA1 repression.

    Evidence ChIP for histone marks, shRNA knockdown with RNA-seq in hippocampal neurons, Arc overexpression in HEK293T

    PMID:36009494

    Open questions at the time
    • Whether Arc binds chromatin directly or through adaptor proteins
    • How nuclear versus cytoplasmic Arc pools are differentially regulated
    • Single lab, awaits independent confirmation of the broad transcriptomic effect

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the capsid-like self-oligomerization of Arc is regulated in neurons, whether it forms functional capsid-like particles at synapses analogous to intercellular transfer vesicles, and the full structural basis of Arc's actin-stabilizing activity remain unresolved.
  • No full-length Arc structure including the disordered linker
  • No reconstituted in vitro system demonstrating direct F-actin stabilization by Arc
  • Mechanism linking capsid-like assembly to synaptic or intercellular signaling functions in vivo

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 5 GO:0060090 molecular adaptor activity 2 GO:0140110 transcription regulator activity 2 GO:0008092 cytoskeletal protein binding 1 GO:0042393 histone binding 1
Localization
GO:0005829 cytosol 4 GO:0005634 nucleus 3 GO:0005886 plasma membrane 3 GO:0031410 cytoplasmic vesicle 3 GO:0005654 nucleoplasm 2 GO:0005856 cytoskeleton 1
Pathway
R-HSA-112316 Neuronal System 6 R-HSA-392499 Metabolism of proteins 4 R-HSA-5653656 Vesicle-mediated transport 4 R-HSA-74160 Gene expression (Transcription) 4 R-HSA-162582 Signal Transduction 3
Partners
AP2M1CACNG2CAMK2BDNM1PICK1RNF216SH3GL2UBE3A

Evidence

Reading pass · 24 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2010 Ube3A (E3 ubiquitin ligase) ubiquitinates Arc protein, leading to its proteasomal degradation; disruption of Ube3A increases Arc levels, causing decreased AMPA receptor number at excitatory synapses Biochemical ubiquitination assays, neuronal knockdown/knockout with AMPA receptor surface quantification Cell High 20211139
2008 Arc interacts with endophilin and dynamin to form a postsynaptic trafficking endosome that promotes endocytosis of AMPA-type glutamate receptors at excitatory synapses, mediating LTD and homeostatic plasticity Co-immunoprecipitation, receptor trafficking assays, Arc knockdown The Journal of neuroscience High 19005037
2008 mGluR-LTD induction in hippocampal neurons causes rapid dendritic translation of Arc; knockdown of Arc prevents mGluR-triggered AMPA receptor endocytosis and LTD, whereas NMDA receptor-induced LTD does not require Arc Arc antisense knockdown, AMPAR endocytosis assay, electrophysiology Neuron High 18614031
2007 Sustained Arc synthesis is required for cofilin phosphorylation, stable expansion of the F-actin cytoskeleton at synaptic sites, and consolidation of LTP in the dentate gyrus in vivo; antisense knockdown of Arc during LTP maintenance reverses LTP and causes loss of nascent F-actin In vivo antisense oligodeoxynucleotide infusion at multiple time points, F-actin staining, cofilin phosphorylation assays, electrophysiology The Journal of neuroscience High 17898216
2012 Arc accumulates specifically at inactive (non-potentiated) synapses via high-affinity interaction with CaMKIIβ not bound to calmodulin; this 'inverse synaptic tagging' correlates with removal of surface GluA1 from individual synapses, and loss of CaMKIIβ abolishes Arc upregulation in silenced synapses Co-immunoprecipitation, live imaging of Arc-GFP in neurons, CaMKIIβ KO mice, surface GluA1 quantification Cell High 22579289
2015 Crystal structures of Arc subdomains reveal a bi-lobar architecture similar to the HIV capsid domain (Ty3/Gypsy retrotransposon origin); the Arc N-terminal lobe contains a unique hydrophobic pocket that mediates intermolecular binding with TARPγ2 (Stargazin) and CaMKII peptides and is essential for Arc's synaptic function X-ray crystallography, co-crystal structures with binding partners, mutagenesis of hydrophobic pocket Neuron High 25864631
2014 The RING domain E3 ubiquitin ligase Triad3A/RNF216 ubiquitinates Arc, causing its rapid proteasomal degradation; Triad3A associates with Arc at clathrin-coated pits and endocytic sites in dendrites and spines; loss of Triad3A accumulates Arc and reduces surface AMPA receptors Co-immunoprecipitation, ubiquitination assay, Triad3A knockdown/KO, AMPAR surface quantification, electrophysiology Neuron High 24945773
2013 Arc localizes to the nucleus where it promotes increased promyelocytic leukemia (PML) nuclear body expression, which decreases GluA1 transcription and synaptic strength; Arc contains distinct nuclear localization signal, nuclear retention domain, and nuclear export signal; nuclear Arc regulates homeostatic plasticity Subcellular fractionation, live imaging, Arc domain mutants, GluA1 transcription assays, homeostatic plasticity electrophysiology Nature neuroscience High 23749147
2010 Arc increases dendritic spine density and regulates spine morphology by increasing the proportion of thin spines; Arc mutants that fail to facilitate AMPAR endocytosis do not increase thin spine proportion; loss of Arc in vivo leads to decreased thin spines and epileptic-like network hyperexcitability Arc overexpression/KO in neurons, spine morphology analysis, surface GluA1 internalization assay, in vivo EEG Proceedings of the National Academy of Sciences High 20921410
2008 The Arc/Arg3.1 promoter contains a ~100 bp synaptic activity-responsive element (SARE) located >5 kb upstream of the transcription initiation site; SARE contains clustered binding sites for CREB, MEF2, and SRF that are necessary and sufficient for rapid activity-induced Arc transcription Luciferase reporter assays in cultured cortical neurons, comparative genomics, transcription factor binding site deletion/mutation analysis Proceedings of the National Academy of Sciences High 19116276
2017 GSK3α and GSK3β phosphorylate Arc protein; GSK3β promotes Arc proteasomal degradation under conditions of de novo Arc synthesis; GSK3α/β inhibition potentiates spine head thinning caused by NMDAR stimulation; Arc mutants resistant to GSK3β-mediated phosphorylation or ubiquitination produce stronger reduction in dendritic spine width In vitro kinase assay, mass spectrometry phosphorylation site mapping, Arc mutant overexpression, spine morphology analysis Frontiers in molecular neuroscience Medium 28670266
2017 Arc binds to the clathrin adaptor protein 2 (AP-2) and to endophilin/dynamin to facilitate clathrin-mediated endocytosis of AMPA receptors; this interaction determines which AMPAR subunits are internalized Co-immunoprecipitation, biochemical endocytosis assays, functional review of published data Seminars in cell & developmental biology Medium 28890421
2015 Purified human Arc protein forms a pyramid-shaped monomer capable of reversible self-association into large soluble oligomers; Arc has two major domains flanking a disordered linker; binding of presenilin-1 peptide induces a large structural change in Arc Recombinant protein purification, limited proteolysis/MS, CD spectroscopy, DLS, AFM, EM The Biochemical journal Medium 25748042
2017 MSK1 kinase is activated downstream of BDNF via the ERK1/2 pathway and induces Arc/Arg3.1 transcription by phosphorylating histone H3 at the Arc promoter; ERK1/2 also directly activates Arc transcription via serum response elements bound by SRF-TCF complexes; CREB Ser133 phosphorylation by MSK1 is not required for BDNF-induced Arc transcription MSK1 knockout neurons, histone phosphorylation ChIP, CREB Ser133Ala knockin, ERK pathway inhibition FEBS open bio Medium 28593137
2015 A chromatin-modifying complex containing histone demethylase PHF8 and acetyltransferase TIP60 is rapidly recruited to the Arc promoter upon synaptic activity; this complex removes the repressive H3K9me2 mark and promotes H3K9acS10P to activate Arc transcription ChIP, gain/loss-of-function of PHF8 and TIP60 in hippocampal neurons, promoter assays, super-resolution microscopy eNeuro Medium 26464965
2018 Arc protein stability is regulated by ubiquitination; Arc knockin mice with mutated predominant ubiquitination sites (ArcKR) show prolonged Arc protein levels, reduced threshold and enhanced amplitude of mGluR-LTD, and cognitive inflexibility in reversal learning without affecting spatial learning Knockin mouse generation, Arc protein degradation assays, mGluR-LTD electrophysiology, behavioral testing Neuron High 29861284
2003 Reelin binds with high affinity to integrin receptors in synaptoneurosomes and activates Arc protein synthesis via an mTOR (rapamycin-sensitive) pathway; this effect is blocked by integrin receptor antagonist echistatin Radiolabeled amino acid incorporation into Arc in synaptoneurosomes, competitive receptor binding, rapamycin and echistatin pharmacology Proceedings of the National Academy of Sciences Medium 12707415
2012 Arc mRNA is regulated by multiple microRNAs binding to its 3'-UTR; miR-34a, miR-193a, and miR-326 downregulate endogenous Arc protein in hippocampal neurons; PNA inhibitors of miR-326 enhance Arc mRNA expression; miR-132 is upregulated by BDNF and LTP but does not directly suppress Arc Luciferase reporter with Arc 3'-UTR, miRNA transfection in neurons, PNA inhibitors, miRNA seed-region mutagenesis, qPCR of synaptoneurosome fractions PloS one Medium 22844515
2017 Arc interacts with PICK1 (protein interacting with C-kinase 1) in brain homogenates and synaptosomes; this interaction increases under depolarizing conditions; the Arc binding region maps to the first 126 amino acids of the PICK1 BAR domain; co-expression causes activity-dependent increases in Arc-PICK1 co-puncta Pulldown from brain lysate, FLIM-FRET interaction assay, co-immunoprecipitation, domain mapping Scientific reports Medium 30279480
2017 Arc lysine acetylation is a post-translational modification that regulates Arc protein stability; chemogenomic screening identified small molecules promoting Arc acetylation that alter Arc expression in BDNF-stimulated cortical neurons Chemogenomic small molecule screen, mass spectrometry identification of acetylation sites, primary cortical neuron assays Nature communications Medium 29162813
2014 Dendritic mGluR5 activation (but not somatic) is required for MEF2-induced synapse elimination; mGluR5 stimulates dendritic translation of Arc, which plays an acute, cell-autonomous, postsynaptic role in MEF2-induced functional and structural synapse elimination Local dendritic vs. somatic mGluR5 pharmacology, Arc knockdown, electrophysiology and spine counting Cell reports Medium 24857654
2021 Arc is locally translated in afferent sensory fibers in the skin in response to inflammatory cues; Arc-deficient mice display exaggerated vasodilation and paw temperatures; injection of Arc-containing extracellular vesicles (EVs) into skin rescues this phenotype, indicating intercellular Arc signaling regulates neurogenic inflammation Ribosome profiling, Arc KO mice, EV injection rescue experiment, infrared thermometry The Journal of neuroscience Medium 34326146
2020 Arc KO mice show attenuated sleep rebound after sleep deprivation, blunted increases in synaptosomal GluA1 and its phosphorylation after sleep deprivation, and blunted suppression of GluA1 mRNA; Arc protein redistributes among nuclear, cytoplasmic, and synaptic compartments during sleep/wake cycles Arc KO mice, polysomnography, synaptoneurosomes Western blot, subcellular fractionation Proceedings of the National Academy of Sciences Medium 32350140
2022 Arc interacts with dynamic chromatin and associates with histone marks for active enhancers (H3K27Ac, H3K9Ac) in hippocampal neurons; Arc knockdown by shRNA alters expression of over 1900 genes including synaptic plasticity, excitability and Alzheimer's disease-associated genes; expression of Arc in HEK293T cells increases transcription of many neuronal genes ChIP for histone marks, shRNA knockdown with RNA-seq, Arc overexpression in HEK293T cells Biomedicines Medium 36009494

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2010 The Angelman Syndrome protein Ube3A regulates synapse development by ubiquitinating arc. Cell 511 20211139
2008 The immediate early gene arc/arg3.1: regulation, mechanisms, and function. The Journal of neuroscience : the official journal of the Society for Neuroscience 414 19005037
2011 New views of Arc, a master regulator of synaptic plasticity. Nature neuroscience 398 21278731
2008 Rapid translation of Arc/Arg3.1 selectively mediates mGluR-dependent LTD through persistent increases in AMPAR endocytosis rate. Neuron 397 18614031
2007 Sustained Arc/Arg3.1 synthesis controls long-term potentiation consolidation through regulation of local actin polymerization in the dentate gyrus in vivo. The Journal of neuroscience : the official journal of the Society for Neuroscience 385 17898216
2009 The Arc of synaptic memory. Experimental brain research 369 19690847
1999 Composite co-activator ARC mediates chromatin-directed transcriptional activation. Nature 363 10235267
2011 Arc in synaptic plasticity: from gene to behavior. Trends in neurosciences 300 21963089
2012 Inverse synaptic tagging of inactive synapses via dynamic interaction of Arc/Arg3.1 with CaMKIIβ. Cell 251 22579289
2009 The geometry of leptin action in the brain: more complicated than a simple ARC. Cell metabolism 231 19187770
2008 Synaptic activity-responsive element in the Arc/Arg3.1 promoter essential for synapse-to-nucleus signaling in activated neurons. Proceedings of the National Academy of Sciences of the United States of America 218 19116276
2016 A rapidly acting glutamatergic ARC→PVH satiety circuit postsynaptically regulated by α-MSH. Nature neuroscience 213 27869800
2010 Arc regulates spine morphology and maintains network stability in vivo. Proceedings of the National Academy of Sciences of the United States of America 212 20921410
2017 Arc protein: a flexible hub for synaptic plasticity and cognition. Seminars in cell & developmental biology 138 28890419
2015 Structural basis of arc binding to synaptic proteins: implications for cognitive disease. Neuron 135 25864631
2002 A component of the ARC/Mediator complex required for TGF beta/Nodal signalling. Nature 135 12167862
2013 Arc in the nucleus regulates PML-dependent GluA1 transcription and homeostatic plasticity. Nature neuroscience 121 23749147
2010 A specific requirement of Arc/Arg3.1 for visual experience-induced homeostatic synaptic plasticity in mouse primary visual cortex. The Journal of neuroscience : the official journal of the Society for Neuroscience 119 20505084
2010 Time-dependent expression of Arc and zif268 after acquisition of fear conditioning. Neural plasticity 97 20592749
2014 Triad3A regulates synaptic strength by ubiquitination of Arc. Neuron 96 24945773
2003 A reelin-integrin receptor interaction regulates Arc mRNA translation in synaptoneurosomes. Proceedings of the National Academy of Sciences of the United States of America 92 12707415
2007 p53 initiates apoptosis by transcriptionally targeting the antiapoptotic protein ARC. Molecular and cellular biology 90 17998337
2006 Clinical and molecular genetic features of ARC syndrome. Human genetics 86 16896922
2012 MicroRNA regulation of the synaptic plasticity-related gene Arc. PloS one 81 22844515
2009 Arachidonic acid, ARC channels, and Orai proteins. Cell calcium 76 19278724
2018 The Temporal Dynamics of Arc Expression Regulate Cognitive Flexibility. Neuron 74 29861284
1985 The bacteriophage P22 arc and mnt repressors. Overproduction, purification, and properties. The Journal of biological chemistry 74 2995361
2006 Ubiquitination and degradation of the anti-apoptotic protein ARC by MDM2. The Journal of biological chemistry 72 17142834
2004 ARC channels: a novel pathway for receptor-activated calcium entry. Physiology (Bethesda, Md.) 70 15546853
2015 A critical evaluation of the activity-regulated cytoskeleton-associated protein (Arc/Arg3.1)'s putative role in regulating dendritic plasticity, cognitive processes, and mood in animal models of depression. Frontiers in neuroscience 69 26321903
2019 Adolescent Alcohol Exposure Epigenetically Suppresses Amygdala Arc Enhancer RNA Expression to Confer Adult Anxiety Susceptibility. Biological psychiatry 67 30827484
2000 Serotonergic regulation of mRNA expression of Arc, an immediate early gene selectively localized at neuronal dendrites. Neuropharmacology 67 10698012
1990 Arc repressor is tetrameric when bound to operator DNA. Biochemistry 67 2271706
2020 Arc/Arg3.1 function in long-term synaptic plasticity: Emerging mechanisms and unresolved issues. The European journal of neuroscience 63 32888346
2015 Arc is a flexible modular protein capable of reversible self-oligomerization. The Biochemical journal 62 25748042
2016 BDNF-induced LTP is associated with rapid Arc/Arg3.1-dependent enhancement in adult hippocampal neurogenesis. Scientific reports 61 26888068
2014 A role for dendritic mGluR5-mediated local translation of Arc/Arg3.1 in MEF2-dependent synapse elimination. Cell reports 61 24857654
2011 The activity-regulated cytoskeletal-associated protein (Arc/Arg3.1) is required for reconsolidation of a Pavlovian fear memory. The Journal of neuroscience : the official journal of the Society for Neuroscience 59 21562269
2007 STIM1 and the noncapacitative ARC channels. Cell calcium 55 17391754
2005 Immediate early gene (ZENK, Arc) expression in the auditory forebrain of female canaries varies in response to male song quality. Journal of neurobiology 55 15898065
1999 Tolerance of Arc repressor to multiple-alanine substitutions. Proceedings of the National Academy of Sciences of the United States of America 55 10051581
2019 An ARC-Regulated IL1β/Cox-2/PGE2/β-Catenin/ARC Circuit Controls Leukemia-Microenvironment Interactions and Confers Drug Resistance in AML. Cancer research 53 30674535
2014 Connecting ears to eye muscles: evolution of a 'simple' reflex arc. Brain, behavior and evolution 52 24776996
2011 Apoptosis inhibitor ARC promotes breast tumorigenesis, metastasis, and chemoresistance. Cancer research 51 22037876
2004 Calcium binding of ARC mediates regulation of caspase 8 and cell death. Molecular and cellular biology 51 15509781
2016 Divergent Regulation of ER and Kiss Genes by 17β-Estradiol in Hypothalamic ARC Versus AVPV Models. Molecular endocrinology (Baltimore, Md.) 46 26726951
2015 Association of SNPs in EGR3 and ARC with Schizophrenia Supports a Biological Pathway for Schizophrenia Risk. PloS one 42 26474411
2018 Arc/Arg3.1 mediates a critical period for spatial learning and hippocampal networks. Proceedings of the National Academy of Sciences of the United States of America 41 30442670
2017 Inverse synaptic tagging: An inactive synapse-specific mechanism to capture activity-induced Arc/arg3.1 and to locally regulate spatial distribution of synaptic weights. Seminars in cell & developmental biology 40 28939038
2020 Arc silence aggravates traumatic neuronal injury via mGluR1-mediated ER stress and necroptosis. Cell death & disease 39 31919348
2014 Arthrogryposis-renal dysfunction-cholestasis (ARC) syndrome: from molecular genetics to clinical features. Italian journal of pediatrics 38 25239142
2017 Regulation of spine structural plasticity by Arc/Arg3.1. Seminars in cell & developmental biology 37 28943393
2021 An mPOA-ARCAgRP pathway modulates cold-evoked eating behavior. Cell reports 36 34380037
2011 Neuroinflammation and the plasticity-related immediate-early gene Arc. Brain, behavior, and immunity 36 21320587
2017 The mechanistic link between Arc/Arg3.1 expression and AMPA receptor endocytosis. Seminars in cell & developmental biology 32 28890421
2017 Transcriptional and post-translational regulation of Arc in synaptic plasticity. Seminars in cell & developmental biology 32 28890422
2008 Caspase-8 and its inhibitors in RCCs in vivo: the prominent role of ARC. Apoptosis : an international journal on programmed cell death 32 18516683
2018 Sleep loss disrupts Arc expression in dentate gyrus neurons. Neurobiology of learning and memory 31 29635031
2013 Involvement of hippocampal Arc in amnesia and its recovery by alcoholic extract of Ashwagandha leaves. Neurobiology of learning and memory 31 24012642
2010 Induction of the apoptosis inhibitor ARC by Ras in human cancers. The Journal of biological chemistry 30 20392691
2005 Regulation of activity-regulated cytoskeleton protein (Arc) mRNA after acute and chronic electroconvulsive stimulation in the rat. Brain research 30 16309632
2017 GSK3α and GSK3β Phosphorylate Arc and Regulate its Degradation. Frontiers in molecular neuroscience 29 28670266
2013 Differential activation of amygdala Arc expression by positive and negatively valenced emotional learning conditions. Frontiers in behavioral neuroscience 29 24367308
2022 Arc Regulates Transcription of Genes for Plasticity, Excitability and Alzheimer's Disease. Biomedicines 28 36009494
2019 Immune inflammation indicators in anal cancer patients treated with concurrent chemoradiation: training and validation cohort with online calculator (ARC: Anal Cancer Response Classifier). Cancer management and research 28 31118786
2017 Arc ubiquitination in synaptic plasticity. Seminars in cell & developmental biology 28 28890418
2016 ARC Syndrome-Linked Vps33B Protein Is Required for Inflammatory Endosomal Maturation and Signal Termination. Immunity 28 27496733
2018 Position- and Time-Dependent Arc Expression Links Neuronal Activity to Synaptic Plasticity During Epileptogenesis. Frontiers in cellular neuroscience 27 30154698
2015 A Neuronal Activity-Dependent Dual Function Chromatin-Modifying Complex Regulates Arc Expression. eNeuro 27 26464965
2012 STIM and Orai proteins and the non-capacitative ARC channels. Frontiers in bioscience (Landmark edition) 27 22201777
2008 Basal and stress-induced modulation of activity-regulated cytoskeletal associated protein (Arc) in the rat brain following duloxetine treatment. Psychopharmacology 27 18704370
2021 Intercellular Arc Signaling Regulates Vasodilation. The Journal of neuroscience : the official journal of the Society for Neuroscience 26 34326146
2020 Loss of Arc attenuates the behavioral and molecular responses for sleep homeostasis in mice. Proceedings of the National Academy of Sciences of the United States of America 26 32350140
2019 Activity-regulated cytoskeleton-associated protein (Arc/Arg3.1) regulates anxiety- and novelty-related behaviors. Genes, brain, and behavior 26 30761730
2022 Molecular physiology of Arc/Arg3.1: The oligomeric state hypothesis of synaptic plasticity. Acta physiologica (Oxford, England) 25 36073248
2021 Role of apoptosis repressor with caspase recruitment domain (ARC) in cell death and cardiovascular disease. Apoptosis : an international journal on programmed cell death 24 33604728
2020 Lactate enhances Arc/arg3.1 expression through hydroxycarboxylic acid receptor 1-β-arrestin2 pathway in astrocytes. Neuropharmacology 24 32294462
2013 Changes in the Egr1 and Arc expression in brain structures of pentylenetetrazole-kindled rats. Pharmacological reports : PR 24 23744421
2005 Is electric arc welding linked to manganism or Parkinson's disease? Toxicological reviews 24 16499406
2020 Activation of the ARCPOMC→MeA Projection Reduces Food Intake. Frontiers in neural circuits 23 33250721
2017 Arc - An endogenous neuronal retrovirus? Seminars in cell & developmental biology 23 28941877
2003 Down-regulation of ARC contributes to vulnerability of hippocampal neurons to ischemia/hypoxia. FEBS letters 23 12753927
2020 Effects of Ketamine on Learning and Memory in the Hippocampus of Rats through ERK, CREB, and Arc. Brain sciences 22 33383707
2013 Taste familiarity is inversely correlated with Arc/Arg3.1 hemispheric lateralization. The Journal of neuroscience : the official journal of the Society for Neuroscience 22 23843540
2011 Altered learning and Arc-regulated consolidation of learning in striatum by methamphetamine-induced neurotoxicity. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 21 22071872
2009 Arc-repressor dimerization on DNA: folding rate enhancement by colocalization. Biophysical journal 21 19450491
2018 Effect of vanadium released from micro-arc oxidized porous Ti6Al4V on biocompatibility in orthopedic applications. Colloids and surfaces. B, Biointerfaces 20 29803152
2016 Rare mutations and hypermethylation of the ARC gene associated with schizophrenia. Schizophrenia research 20 27464451
2000 Activation of an effector immediate-early gene arc by methamphetamine. Annals of the New York Academy of Sciences 20 11085305
2020 The continuing arc toward phototropic enlightenment. Journal of experimental botany 19 31907539
2019 The activity-regulated cytoskeleton-associated protein, Arc/Arg3.1, influences mouse cocaine self-administration. Pharmacology, biochemistry, and behavior 19 31682894
2016 Developmental Exposure to Cocaine Dynamically Dysregulates Cortical Arc/Arg3.1 Modulation in Response to a Challenge. Neurotoxicity research 19 27832448
2014 A novel role for the apoptosis inhibitor ARC in suppressing TNFα-induced regulated necrosis. Cell death and differentiation 19 24440909
2014 Fear extinction requires Arc/Arg3.1 expression in the basolateral amygdala. Molecular brain 19 24758170
2018 Arc/Arg3.1 has an activity-regulated interaction with PICK1 that results in altered spatial dynamics. Scientific reports 17 30279480
2017 MSK1 regulates transcriptional induction of Arc/Arg3.1 in response to neurotrophins. FEBS open bio 17 28593137
2017 Community Structure of Lithotrophically-Driven Hydrothermal Microbial Mats from the Mariana Arc and Back-Arc. Frontiers in microbiology 17 28970817
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