Affinage

CPEB3

Cytoplasmic polyadenylation element-binding protein 3 · UniProt Q8NE35

Length
698 aa
Mass
76.0 kDa
Annotated
2026-06-09
81 papers in source corpus 37 papers cited in narrative 36 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

CPEB3 is a sequence-specific RNA-binding protein that acts predominantly as a translational repressor of target mRNAs and serves as a molecular substrate for the persistence of synaptic plasticity and long-term memory (PMID:17024188, PMID:26074003). It belongs to a distinct class of CPEBs that recognizes RNA elements unlike those of CPEB1 and represses translation without requiring the AAUAAA element or CPSF (PMID:17024188); in its basal state it represses targets in part by recruiting the Tob–Caf1 deadenylase complex to promote deadenylation and mRNA decay (PMID:21336257). Across neurons it suppresses synthesis of plasticity proteins including GluA2/GluA1, PSD95 and NMDA receptors, and its genetic loss elevates these targets while enhancing memory and altering LTP/LTD (PMID:17024188, PMID:24155305, PMID:25404896). CPEB3 activity is gated by a switchable conformational state: basally it is SUMOylated, soluble, and partitions into P bodies through direct interaction with the P-body component GW182, where target mRNAs are translationally silenced (PMID:26074071, PMID:31416913, PMID:36068334); neuronal stimulation drives de-SUMOylation and prion-like amyloid aggregation—organized around a defined 49-residue ordered core (L103–F151) within the first prion-like domain—that relocates CPEB3 to polysomes to activate translation, a state required for LTP maintenance and spatial memory (PMID:26074071, PMID:26074003, PMID:40480223, PMID:34081983). Activation is further controlled by Neuralized1-mediated non-proteolytic ubiquitination, which promotes target synthesis, spine growth and plasticity (PMID:22153079), while calpain 2 cleaves the N-terminal repression domain upon NMDAR activation to de-repress targets (PMID:22711986). A separate nuclear pool, imported via IPO5 binding to RRM1 downstream of NMDAR/RanBP1 signaling, binds Stat5b and suppresses Stat5b-dependent transcription of EGFR (PMID:22730302, PMID:20639532). Beyond the nervous system, CPEB3 represses translation of oncogenic targets including IL-6R, JAK1, MTDH and NFE2L1, and its abundance is controlled by TRAIP-mediated proteasomal degradation (PMID:32653013, PMID:32968053, PMID:33146632, PMID:41832516). The intrinsically disordered N-terminal region lacks stable fold, and PKA/CaMKII phosphorylate B-region–containing isoforms as an additional regulatory layer (PMID:26915047, PMID:27256982, PMID:35658951).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 2006 High

    Established CPEB3 as a sequence-specific RNA-binding translational repressor distinct from CPEB1, answering whether it functions in classical cytoplasmic polyadenylation.

    Evidence SELEX, footprinting, tethered reporter assays and RNAi in neurons, with GluR2 as an in vivo target

    PMID:17024188

    Open questions at the time
    • Did not define the activation switch from repression to translation
    • Full target repertoire unknown at this stage
  2. 2010 High

    Identified a nuclear function for CPEB3 as a transcriptional co-repressor, showing it acts beyond cytoplasmic translation control.

    Evidence Co-IP, reporter assays and RNAi linking nuclear CPEB3 to Stat5b inhibition and EGFR regulation in neurons

    PMID:20639532

    Open questions at the time
    • Mechanism of nuclear import not yet defined
    • How Stat5b activity is inhibited without affecting DNA binding unresolved
  3. 2011 High

    Defined two opposing regulatory inputs: deadenylation-based repression and ubiquitin-based activation, clarifying how CPEB3 toggles target fate.

    Evidence Reconstituted CPEB3–Tob–Caf1 ternary complex and dominant-negative analysis; Neuralized1 in vitro ubiquitination with gain/loss-of-function in hippocampal neurons and mice

    PMID:21336257 PMID:22153079

    Open questions at the time
    • How non-proteolytic ubiquitination converts CPEB3 to an activator not mechanistically resolved
    • Coupling between deadenylase recruitment and the SUMO/aggregation switch unknown
  4. 2012 High

    Placed CPEB3 downstream of NMDAR/calcium signaling via two mechanisms—calpain 2 cleavage of its repression domain and IPO5-mediated nuclear import.

    Evidence Pharmacology/RNAi and domain-specific cleavage assays for calpain 2; Co-IP, domain mapping and RanBP1 manipulation for IPO5/CRM1 trafficking

    PMID:22711986 PMID:22730302

    Open questions at the time
    • Relative contribution of cleavage vs. aggregation to activation not quantified
    • Trigger that partitions CPEB3 between cytoplasmic and nuclear fates unclear
  5. 2013 High

    Demonstrated through knockout that CPEB3 represses multiple plasticity proteins and constrains memory, establishing its physiological role at glutamatergic synapses.

    Evidence CPEB3 KO mice with behavioral, electrophysiological and Western blot analysis of PSD95, NMDARs, GluA1

    PMID:24155305

    Open questions at the time
    • Did not address the activation-dependent translational role
    • Did not distinguish direct vs. indirect target regulation
  6. 2014 High

    Linked CPEB3 loss to CaMKIIα hyperactivation and impaired depotentiation, embedding it in synaptic state-switching circuitry.

    Evidence CPEB3 KO electrophysiology, phospho-GluA1/CaMKIIα Westerns and pharmacological CaMKIIα rescue

    PMID:25404896

    Open questions at the time
    • Whether CaMKIIα effects are direct translational targets or downstream consequences unclear
  7. 2015 High

    Resolved the central activation switch: SUMOylation keeps CPEB3 soluble and repressive, while de-SUMOylation enables prion-like aggregation that activates translation and sustains memory.

    Evidence SUMOylation and SUMO-fusion assays, yeast prion assays with prion-domain deletion mapping, and CPEB3 KO LTP/spatial memory studies

    PMID:26074003 PMID:26074071 PMID:26074072

    Open questions at the time
    • Enzymes mediating de-SUMOylation in neurons not identified
    • Molecular basis by which aggregation activates rather than represses translation incompletely defined
  8. 2016 High

    Extended CPEB3 repression to diverse targets and tissues (TRPV1 in nociception, GluA2 in cerebellar cells, Megf10 in retina) and identified isoform-specific phosphorylation as a regulatory layer.

    Evidence CPEB3/TRPV1 double-KO epistasis, cerebellar stellate cell electrophysiology, retinal mosaic analysis, and in vitro PKA/CaMKII kinase assays on B-region isoforms

    PMID:26915043 PMID:26915047 PMID:27256982 PMID:27681423 PMID:27822178

    Open questions at the time
    • Functional consequence of B-region phosphorylation on aggregation/repression not fully resolved
    • Several target findings are single-lab
  9. 2019 High

    Connected the SUMO switch to subcellular compartmentalization, showing CPEB3 distributes between P bodies (repressive) and polysomes (active) and phase-separates on bound mRNA.

    Evidence Subcellular and polysome fractionation, P-body co-localization, and in vitro phase separation of recombinant SUMOylated CPEB3

    PMID:31416913

    Open questions at the time
    • Relationship between liquid phase separation and irreversible amyloid aggregation unresolved
    • P-body targeting machinery not yet identified at this point
  10. 2020 High

    Generalized CPEB3 as a tumor-suppressive translational repressor across cancers, repressing IL-6R, JAK1, MTDH and NFE2L1 to restrain oncogenic signaling.

    Evidence RIP/RIP-seq, luciferase 3'UTR assays, KD/OE and a Cpeb3 KO carcinogenesis mouse model

    PMID:32366381 PMID:32653013 PMID:32968053 PMID:33146632

    Open questions at the time
    • Whether cancer targets are repressed by the same SUMO/aggregation switch as neuronal targets untested
    • Some target reports are single-lab Medium-confidence
  11. 2021 High

    Broadened the in vivo target set (Nr3c1, maternal mRNAs) and defined roles in fear extinction and early embryogenesis, including an mRNA-stabilizing rather than repressive activity.

    Evidence Genome-wide RIP-seq, CPEB3 KO behavior, calcium imaging and BDNF rescue; oocyte transcriptomics and developmental phenotyping

    PMID:33941859 PMID:38786074

    Open questions at the time
    • Determinants of repression vs. stabilization of bound mRNAs unclear
    • Embryonic mechanism rests on correlative transcriptomics
  12. 2022 High

    Identified the direct P-body targeting interaction (CPEB3–GW182) and structurally characterized the intrinsically disordered region, mapping the architecture underlying compartmentalization.

    Evidence Microscale thermophoresis defining CPEB3–GW182 binding, RIP/reporter assays for ADAR1 repression, and residue-level NMR of the 426-residue IDR

    PMID:35658951 PMID:36068334

    Open questions at the time
    • Structural elements of the IDR not all functionally validated
    • How GW182 binding integrates with SUMO state unresolved
  13. 2023 Medium

    Dissected the prion-like domain's roles: a low-complexity motif directs neuronal RNP-granule localization required for local protein synthesis, and the prion domain interacts with tau.

    Evidence Live imaging with LCM deletion mutants and AMPA trafficking readouts; NMR mapping of PRD1–tau interaction; QBP1 aggregation-inhibition with transgenic mouse memory deficits (preprint)

    PMID:36716374 PMID:39908090 PMID:bio_10.1101_2025.01.27.635080

    Open questions at the time
    • Physiological relevance of CPEB3–tau interaction in vivo untested
    • QBP1 memory data remain a preprint
  14. 2025 High

    Delivered atomic-resolution structure of the CPEB3 amyloid core and demonstrated its necessity for correct localization and translational function in neurons.

    Evidence Cryo-EM of fibrils defining the L103–F151 core, cryo-FIB/cryo-ET in neurons, and deletion-mutant functional and localization assays

    PMID:34081983 PMID:40480223

    Open questions at the time
    • Whether the in vitro fibril core matches the functional in-cell aggregate not fully established
    • Association with multivesicular bodies functionally uncharacterized
  15. 2026 Medium

    Established TRAIP-mediated proteasomal degradation as a regulator of CPEB3 abundance controlling oncogenic mTORC1 signaling.

    Evidence Co-IP, ubiquitylation assays, epistasis rescue and xenografts in gastric cancer cells

    PMID:41832516

    Open questions at the time
    • Single-lab study
    • Relationship to non-proteolytic ubiquitination by Neuralized1 not reconciled

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the SUMO state, phase separation, amyloid aggregation, ubiquitination and proteolysis are mechanistically coupled to flip CPEB3 from a repressor to a translational activator on individual target mRNAs remains unresolved.
  • No unified biochemical model linking conformational state to repression vs. activation
  • DeSUMOylating and signaling enzymes acting on neuronal CPEB3 not identified
  • Determinants distinguishing repressed vs. stabilized targets unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003723 RNA binding 5 GO:0045182 translation regulator activity 4 GO:0140110 transcription regulator activity 2
Localization
GO:0005634 nucleus 2 GO:0005829 cytosol 2
Pathway
R-HSA-112316 Neuronal System 3 R-HSA-392499 Metabolism of proteins 3 R-HSA-8953854 Metabolism of RNA 3
Partners
CAPN2CNOT7GW182IPO5NEURL1STAT5BTOBTRAIP
Complex memberships
CPEB3-Tob-Caf1 deadenylase complex

Evidence

Reading pass · 36 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2006 CPEB3 and CPEB4 bind different RNA sequences than CPEB1, as determined by SELEX, RNA structure probing, and footprinting, placing them in a distinct class of RNA-binding proteins. In transfected neurons, CPEB3 represses translation of a reporter RNA in tethered function assays; NMDA receptor activation stimulates translation. CPEB3-mediated translation does not require the AAUAAA cis-element or cleavage and polyadenylation specificity factor (CPSF), unlike CPEB1-induced polyadenylation. CPEB3 binds GluR2 (GluA2) mRNA in vitro and in vivo, and RNAi knockdown of CPEB3 in neurons elevates GluR2 protein levels, establishing CPEB3 as a translational repressor of GluR2. SELEX, RNA structure probing, RNA footprinting, tethered function assays in transfected neurons, in vitro and in vivo RNA binding, RNAi knockdown The EMBO journal High 17024188
2011 CPEB3 is activated by Neuralized1, an E3 ubiquitin ligase. Neuralized1-mediated non-proteolytic ubiquitination of CPEB3 in hippocampal cultures leads to growth of new dendritic spines and increased GluA1 and GluA2 (AMPA receptor subunits), which are CPEB3 target mRNAs. Conditional overexpression of Neuralized1 increases GluA1, GluA2, spine number, and functional synapses; inhibition of Neuralized1 reduces these and impairs hippocampal-dependent memory and synaptic plasticity. Co-immunoprecipitation, in vitro ubiquitination assay, hippocampal neuron culture, conditional transgenic mouse overexpression/inhibition, behavioral and electrophysiological assays Cell High 22153079
2011 CPEB3 recruits the Caf1 deadenylase to target mRNAs via direct binding to Tob (anti-proliferative protein), forming a ternary CPEB3–Tob–Caf1 complex. The C-terminal RNA-binding domain of CPEB3 binds the C-terminal unstructured region of Tob; Tob then recruits Caf1. CPEB3-accelerated deadenylation and mRNA decay is abrogated by dominant-negative mutants of either Caf1 or Tob. Direct binding assays, co-immunoprecipitation, dominant-negative mutant analysis, deadenylation assay, tethering assay The EMBO journal High 21336257
2012 NMDA receptor activation causes calpain 2-mediated proteolysis of the N-terminal repression motif of CPEB3, but not its C-terminal RNA-binding domain. The cleaved CPEB3 fragment retains RNA binding but fails to repress translation, thereby de-repressing CPEB3 target mRNAs (including EGFR) at the translational level. Calcium influx through NMDARs activates calpain 2, which proteolyzes CPEB3. Pharmacological inhibition, RNAi knockdown of calpain 2, domain-specific cleavage analysis, Western blot, translation assays in NMDA-stimulated neurons Molecular and cellular biology High 22711986
2012 IPO5 (importin 5) facilitates nuclear import of CPEB3 by binding to the RRM1 domain of CPEB3. CRM1 facilitates nuclear export via a leucine-containing motif of CPEB3. NMDAR signaling increases RanBP1 expression and reduces cytoplasmic GTP-bound Ran, which enhances CPEB3–IPO5 interaction and accelerates nuclear import of CPEB3. In the nucleus, CPEB3 binds Stat5b and suppresses Stat5b-dependent transcription. Co-immunoprecipitation, domain mapping, RanBP1 overexpression, pharmacological NMDA stimulation, nuclear fractionation, reporter assays Nucleic acids research High 22730302
2010 CPEB3 interacts with Stat5b in the nucleus and inhibits Stat5b transcriptional activity without disrupting Stat5b dimerization, DNA binding, or nuclear localization. NMDA receptor activation causes nuclear accumulation of CPEB3. EGFR is a target gene transcriptionally activated by Stat5b and negatively regulated by CPEB3 in neurons; CPEB3 knockdown increases EGFR expression and alters EGF-induced downstream signaling kinetics. Co-immunoprecipitation, reporter assay, RNAi knockdown, NMDA stimulation, nuclear fractionation, Western blot Nucleic acids research High 20639532
2015 CPEB3 is SUMOylated in hippocampal neurons in vitro and in vivo under basal (unstimulated) conditions, in which state it is soluble and acts as a translational repressor. Following neuronal stimulation, CPEB3 is de-SUMOylated, forms aggregates/oligomers, and promotes translation of target mRNAs. A chimeric CPEB3 fused to SUMO cannot form aggregates and cannot activate translation of target mRNAs, establishing SUMOylation as an inhibitory constraint on CPEB3 aggregation and activity. SUMOylation assay in neurons (in vitro and in vivo), chimeric SUMO-fusion protein, aggregation assay, translational reporter assay, neuronal stimulation paradigm Cell reports High 26074071
2015 CPEB3 forms heritable aggregates (a hallmark of prions) when expressed in yeast. Deletion analysis of the CPEB3 prion domain revealed a tripartite organization: two aggregation-promoting domains flanking a regulatory module that mediates interaction with the actin cytoskeleton. CPEB3 aggregation is necessary for its function in mouse neurons, confirming it as a functional prion. Yeast prion assay, deletion analysis, actin interaction assay, mouse neuronal studies Cell reports High 26074072
2015 CPEB3 aggregation and prion-like activity are required for maintenance of hippocampal long-term potentiation and hippocampus-dependent spatial memory. Genetic ablation of CPEB3 impairs maintenance of both. CPEB3 levels and aggregation increase after neuronal activity, supporting a model whereby CPEB3 aggregates function as active translational regulators for memory persistence. CPEB3 knockout mouse, LTP electrophysiology, Morris water maze spatial memory test, Western blot for aggregation state Neuron High 26074003
2013 CPEB3 knockout mice display enhanced hippocampus-dependent memory and facilitated LTD. Molecular analysis shows elevated translational levels of PSD95, NMDA receptors, and GluA1 in CPEB3 KO neurons, establishing CPEB3 as a translational repressor of multiple plasticity-related proteins at glutamatergic synapses. CPEB3 knockout mouse, contextual fear conditioning, Morris water maze, electrophysiology, Western blot, molecular characterization of PSD95, NMDARs, GluA1 The Journal of neuroscience High 24155305
2019 Basal, SUMOylated CPEB3 localizes to P bodies (membraneless cytoplasmic processing bodies enriched in translationally repressed mRNA). After neuronal stimulation, CPEB3 moves to polysomes to promote translation of target mRNAs. SUMOylation state controls this distribution. In vitro, SUMOylated CPEB3 recombinant protein undergoes phase separation when bound to a specific mRNA target. Subcellular fractionation, immunofluorescence co-localization with P body markers, polysome fractionation, in vitro phase separation assay with recombinant SUMOylated CPEB3 Proceedings of the National Academy of Sciences of the United States of America High 31416913
2014 CPEB3 deficiency leads to elevated activation of CaMKIIα, increased Ser831 phosphorylation of GluA1, and slow degradation of PSD95 and GluA1 under NMDA-induced chemical LTD. CPEB3 KO hippocampus shows impaired NMDAR-dependent synaptic depotentiation; pharmacological suppression of CaMKIIα during the depotentiation-initiating phase rescues LTP reversal in KO hippocampus. CPEB3 KO mouse, electrophysiology (depotentiation, c-LTD), Western blot for CaMKIIα activation and phospho-GluA1, pharmacological CaMKIIα inhibition Frontiers in cellular neuroscience High 25404896
2020 CPEB3 directly binds to the 3'UTR of IL-6R mRNA and reduces IL-6R protein levels, thereby decreasing phospho-STAT3 in colorectal cancer cells. CPEB3 knockdown increases IL-6R expression, activates STAT3, and promotes M2-like TAM polarization via increased CCL2 secretion. These findings place CPEB3 upstream of the IL-6R/STAT3 axis as a post-transcriptional repressor. RNA immunoprecipitation, luciferase reporter assay, RIP, CPEB3 overexpression/knockdown, co-culture, Western blot for p-STAT3 Journal of experimental & clinical cancer research : CR Medium 32653013
2020 NFE2L3 induces CPEB3 gene expression, and CPEB3 then binds to the NFE2L1 3'UTR to repress NFE2L1 mRNA translation, reducing polysome formation on NFE2L1 mRNA. This NFE2L3-CPEB3-NFE2L1 translational repression axis maintains basal proteasome activity in cancer cells. RNAi double knockdown, polysome profiling, reporter assay, Western blot for proteasome subunits and NFE2L1 Molecular and cellular biology Medium 32366381
2020 CPEB3 binds to the 3'UTR of MTDH mRNA and suppresses its translation in hepatocellular carcinoma cells in vivo and in vitro, inhibiting EMT and metastasis. RNA immunoprecipitation identified transcriptome-wide CPEB3-bound mRNAs; MTDH was confirmed as a direct target. Cpeb3 knockout mice showed increased susceptibility to carcinogen-induced hepatocarcinogenesis and lung metastasis. RNA immunoprecipitation (RIP-seq), luciferase reporter assay (3'UTR binding), Western blot for MTDH, cpeb3 KO mouse, in vivo carcinogenesis model Cell death & disease High 32968053
2016 CPEB3 suppresses GluA2 protein synthesis in a topologically graded manner in cerebellar stellate cells. Action potentials produce graded dendritic depolarizations that elevate CPEB3 protein at proximal dendrites; CPEB3 then binds GluA2 mRNA and suppresses GluA2 translation, leading to a distance-dependent increase in synaptic GluA2-containing AMPARs. Activity-induced CPEB3 expression requires increased Ca2+ and PKC activation. CPEB3 overexpression/knockdown in mouse cerebellar stellate cells, electrophysiology, live imaging, pharmacological Ca2+ and PKC manipulation, Western blot Cell reports Medium 27681423
2020 Stress suppresses GluA1 protein synthesis in cerebellar Bergmann glial cells via an adrenergic/adenylyl cyclase 5 (AC5)/CPEB3 pathway. CPEB3 binds GluA1 mRNA and regulates its translation; mice lacking CPEB3 do not show stress-induced GluA1 reduction, and deletion of AC5 prevents GluA1 suppression. This reduces AMPA receptor-mediated currents and causes retraction of glial lateral processes. CPEB3 knockout mouse, AC5 knockout mouse, β-adrenergic receptor blocker pharmacology, electrophysiology, immunofluorescence, Western blot The Journal of neuroscience High 32229518
2021 CPEB3 translationally suppresses Nr3c1 (glucocorticoid receptor) mRNA in hippocampal neurons; a genome-wide screen (RIP-seq) of CPEB3-bound transcripts identified Nr3c1 as a target. CPEB3-KO neurons show elevated GR expression, increased corticosterone-induced calcium influx, and decreased BDNF mRNA and protein, linking CPEB3 loss to impaired fear extinction. CPEB3 KO mouse, genome-wide RIP-seq, behavioral fear conditioning/extinction paradigm, Western blot, calcium imaging, intracerebroventricular BDNF delivery rescue Neuropsychopharmacology High 33941859
2016 CPEB3 suppresses translation of TRPV1 mRNA in dorsal root ganglia neurons. CPEB3-KO mice show hypersensitivity to noxious heat; CPEB3/TRPV1 double-KO mice phenocopy TRPV1-KO mice with severely impaired thermosensation, establishing CPEB3 as a translational repressor of TRPV1 upstream of thermal nociception. CPEB3 KO mouse, TRPV1 KO mouse, CPEB3/TRPV1 double-KO mouse, conditional KO, behavioral thermal/mechanical nociception tests, Western blot for TRPV1 PloS one High 26915043
2022 CPEB3 interacts with the 3'UTR of ADAR1 mRNA through binding to CPEB nucleotide elements, inhibits ADAR1 translation by localizing ADAR1 mRNA to P bodies, and thereby suppresses ADAR1-mediated RNA editing in gastric cancer cells. Microscale thermophoresis revealed direct interaction between CPEB3 (residues 440–698) and GW182 (residues 403–860), a major P-body component, mediating P-body targeting. RNA immunoprecipitation, luciferase reporter assay (3'UTR), P body co-localization, microscale thermophoresis (direct protein-protein interaction), KO/KD functional assays Oncogene High 36068334
2023 CPEB3's low-complexity motif (LCM) mediates protein-protein interactions essential for localization to neuronal DCP1-bodies (RNP granules). After chemical LTP induction, both translation-promoting CPEB3 and translation-inhibiting CPEB1 are packaged into neuronal RNP granules, but only CPEB3 is repackaged at later time points. This localization is critical for CPEB3's functional influence on local protein synthesis (measured as AMPA receptor insertion into the membrane and synaptic localization). Fluorescence microscopy (live imaging and fixed), co-localization with DCP1-body markers, CPEB3 LCM deletion mutants, chemical LTP, AMPA receptor trafficking assay Proceedings of the National Academy of Sciences of the United States of America High 36716374
2022 CPEB3 is increased in FMRP-knockout (Fmr1 KO) hippocampal neurons and acts as an upstream effector of elevated GluA2 mRNA transcription in dendrites. Increased CPEB3 drives elevated GluA2 subunit expression, switches synaptic AMPA receptors from GluA2-lacking (Ca2+-permeable) to GluA2-containing (Ca2+-impermeable) at CA1 inhibitory interneurons, and reduces inhibitory synaptic transmission. Single-molecule mRNA detection (smFISH), Fmr1 KO mouse, CPEB3 knockdown, electrophysiology, Western blot Cell reports High 35675768
2025 Cryo-EM structure of amyloid fibrils formed in vitro from the first prion-like domain of human CPEB3 reveals a 49-residue ordered core (L103–F151). CPEB3 lacking this segment forms abnormal puncta in cells, localizes away from P bodies toward stress granules, and lacks the ability to influence protein synthesis in neurons. Cryo-FIB milling and cryo-ET of neuronal cells reveal CPEB3-GFP signal associated with multivesicular bodies and bundled filaments. Cryo-EM structure determination, cryo-focused ion beam milling, cryo-electron tomography in neuronal cells, deletion mutant functional assay, subcellular localization (immunofluorescence/GFP), translation reporter assay, cell viability assay Structure (London, England : 1993) High 40480223
2021 CPEB3 stabilizes a subset of maternal mRNAs with long 3'UTRs enriched in cytoplasmic polyadenylation elements; CPEB3-depleted oocytes undergo normal meiosis but show early embryonic arrest due to disrupted transcriptome and aberrant protein expression, leading to failure of embryonic transcription initiation. Cpeb3-mutant mouse oocytes, transcriptomic analysis, protein expression analysis, developmental phenotyping Cells Medium 38786074
2016 CPEB3 suppresses translation of Megf10 mRNA during the first postnatal week; in CPEB3-KO retinas, elevated MEGF10 expression (a homotypic repulsion mediator) disrupts the mosaic spatial organization of ON starburst amacrine cells. This identifies CPEB3 as a translational repressor of Megf10 RNA with a role in shaping retinal mosaic arrangement. CPEB3 KO mouse, Western blot, immunofluorescence, retinal mosaic analysis Frontiers in molecular neuroscience Medium 27822178
2020 CPEB3 functions as a translational repressor of JAK1 mRNA by binding to its 3'UTR, thereby inhibiting JAK/STAT signaling in colorectal cancer cells; CPEB3 knockdown activates JAK-STAT signaling and promotes proliferation and metastasis. RNA-binding protein immunoprecipitation, luciferase reporter assay (3'UTR), CPEB3 overexpression/knockdown, Western blot for JAK/STAT pathway components Aging Medium 33146632
2016 Loss of CPEB3 activity in high-grade gliomas is caused by expression of alternatively spliced variants lacking the B-region, which overlaps with the kinase recognition site, reducing phosphorylation of CPEB3 in tumor samples. Protein Kinase A and CaMKII robustly phosphorylate CPEB3 in vitro and in primary hippocampal neurons, specifically at isoforms containing exon 7 (B-region). In vitro kinase assay (PKA and CaMKII), phosphospecific antibody, splicing/isoform analysis, kainate-induced status epilepticus mouse model, Western blot PloS one / Oncotarget Medium 26915047 27256982
2022 CPEB3 binds to the CPE signal in the p53 mRNA 3'UTR and stabilizes p53 mRNA expression in bladder cancer cells. CPEB3-mediated p53 mRNA stabilization is part of the circKDM1A/miR-889-3p/CPEB3/p53 axis that suppresses bladder cancer progression. Dual-luciferase reporter assay, RIP assay, CPEB3 overexpression/knockdown, Western blot iScience Medium 38632984
2023 The first prion domain (PRD1) of CPEB3 interacts with the VQIVYKPVDLSKV segment of tau and inhibits tau-K18 aggregation; this interaction simultaneously enhances PRD1 fibril formation. The PRD1-Q region is specifically responsible for inhibiting tau-K18 aggregation. NMR relaxation spectroscopy, fibril formation assays, subdomain peptide mapping The journal of physical chemistry. B Medium 39908090
2022 NMR spectroscopic characterization of the 426-residue intrinsically disordered region (IDR) of human CPEB3 reveals that it lacks stable folded structure. Residues M1–P29 adopt a helical+disordered motif; residues 86–93 and 166–175 form polyproline II helices; residues 200–250 contain three partially populated α-helices; residues 345–355 (NLS) form a modestly populated α-helix potentially mediating STAT5B binding. Solution-state NMR spectroscopy (chemical shift, relaxation), secondary structure analysis BMC biology Medium 35658951
2021 The first prion subdomain PRD1 of mouse CPEB3 autonomously forms amyloid fibrils in vitro and punctate-like structures in vivo. A 94-residue PRD1-core and a 23-residue peptide (E124–H145) display high aggregation propensity; solid-state NMR reveals a β-rich core of ~40 amino acids at the N-terminus of PRD1-core. In vitro fibril formation assay, electron microscopy, X-ray diffraction, solution-state and solid-state NMR, deuterium exchange, in vivo puncta formation Journal of molecular biology High 34081983
2023 CPEB3 prion-like aggregation is inhibited in vitro by the anti-amyloidogenic polyglutamine binding peptide 1 (QBP1-M8) without affecting CPEB3 phase separation. Transgenic mice constitutively expressing QBP1 show impaired consolidation of hippocampal-dependent memories (at 24h) and reduced CPEB3 oligomerization in hippocampal extracts, but no effect on short-term memory. In vitro aggregation inhibition assay, transgenic mouse behavioral phenotyping, biochemical analysis of CPEB3 oligomerization state bioRxivpreprint Medium bio_10.1101_2025.01.27.635080
2026 TRAIP E3 ubiquitin ligase (transcriptionally activated by SOX9) mediates poly-ubiquitylation and proteasomal degradation of CPEB3 in gastric cancer cells. This relieves CPEB3-mediated translational repression of oncogenic targets, leading to hyperactivation of mTORC1 signaling. Epistatic rescue experiments show TRAIP's oncogenic effects are almost entirely dependent on CPEB3 degradation. Co-immunoprecipitation, ubiquitylation assay, ChIP, luciferase reporter assay, shRNA knockdown, overexpression, xenograft mouse model, epistasis rescue experiments World journal of surgical oncology Medium 41832516
2025 CPEB3 binds to STAT3 mRNA and inhibits its translation; reduced CPEB3 in epileptic mice results in elevated STAT3 and p-STAT3, increased STAT3 nuclear translocation, and enhanced STAT3-mediated transcription of GluN1, GluN2A, and GluN2B NMDAR subunits, increasing neuronal excitability. RNA immunoprecipitation (RIP), chromatin immunoprecipitation (ChIP), AAV-mediated CPEB3 overexpression/knockdown in mice, behavioral epilepsy assays, Western blot, RT-qPCR Molecular medicine (Cambridge, Mass.) Medium 39994587
2023 Neuralized1-mediated ubiquitination of CPEB3 in spinal dorsal horn neurons promotes production of GluA1, GluA2, and PSD95 and augments GluA1-containing AMPA receptors in the membrane, contributing to neuropathic pain after spinal nerve ligation. Knockdown of spinal CPEB3 or Neuralized1 reduces AMPA receptor expression and mechanical allodynia. Co-immunoprecipitation (Co-IP), AAV-mediated shRNA knockdown and overexpression in rat spinal cord, Western blot, immunofluorescence, behavioral pain tests ACS chemical neuroscience Medium 37644621
2020 CPEB1 and CPEB3 regulate translation of FosB mRNA in the nucleus accumbens following cocaine administration. Dominant-negative CPEB1/3 mice show decreased locomotor sensitization, conditioned place preference, and cocaine-induced synaptic depression in the NAc core. FosB is identified as a novel translational target of CPEBs, and CPEB is reduced after cocaine injections in transgenic mice. Conditional transgenic dominant-negative CPEB1/3 mouse, behavioral assays (locomotor sensitization, CPP), electrophysiology (synaptic depression), Western blot Frontiers in cellular neuroscience Medium 32742260

Source papers

Stage 0 corpus · 81 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2006 A genomewide search for ribozymes reveals an HDV-like sequence in the human CPEB3 gene. Science (New York, N.Y.) 220 16990549
2006 CPEB3 and CPEB4 in neurons: analysis of RNA-binding specificity and translational control of AMPA receptor GluR2 mRNA. The EMBO journal 193 17024188
2015 The Persistence of Hippocampal-Based Memory Requires Protein Synthesis Mediated by the Prion-like Protein CPEB3. Neuron 167 26074003
2011 Neuralized1 activates CPEB3: a function for nonproteolytic ubiquitin in synaptic plasticity and memory storage. Cell 158 22153079
2020 CPEB3 inhibits epithelial-mesenchymal transition by disrupting the crosstalk between colorectal cancer cells and tumor-associated macrophages via IL-6R/STAT3 signaling. Journal of experimental & clinical cancer research : CR 102 32653013
2015 The CPEB3 Protein Is a Functional Prion that Interacts with the Actin Cytoskeleton. Cell reports 97 26074072
2015 SUMOylation Is an Inhibitory Constraint that Regulates the Prion-like Aggregation and Activity of CPEB3. Cell reports 95 26074071
2019 CPEB3 inhibits translation of mRNA targets by localizing them to P bodies. Proceedings of the National Academy of Sciences of the United States of America 70 31416913
2013 Deletion of CPEB3 enhances hippocampus-dependent memory via increasing expressions of PSD95 and NMDA receptors. The Journal of neuroscience : the official journal of the Society for Neuroscience 70 24155305
2011 Anti-proliferative protein Tob negatively regulates CPEB3 target by recruiting Caf1 deadenylase. The EMBO journal 69 21336257
2019 Long non-coding RNA HCG11 modulates glioma progression through cooperating with miR-496/CPEB3 axis. Cell proliferation 62 31310044
2016 MicroRNA-107: a novel promoter of tumor progression that targets the CPEB3/EGFR axis in human hepatocellular carcinoma. Oncotarget 61 26497556
2020 NFE2L1 and NFE2L3 Complementarily Maintain Basal Proteasome Activity in Cancer Cells through CPEB3-Mediated Translational Repression. Molecular and cellular biology 42 32366381
2012 NMDAR signaling facilitates the IPO5-mediated nuclear import of CPEB3. Nucleic acids research 42 22730302
2010 The human HDV-like CPEB3 ribozyme is intrinsically fast-reacting. Biochemistry 39 20524672
2010 A novel role of CPEB3 in regulating EGFR gene transcription via association with Stat5b in neurons. Nucleic acids research 39 20639532
2017 Mir-452-3p: A Potential Tumor Promoter That Targets the CPEB3/EGFR Axis in Human Hepatocellular Carcinoma. Technology in cancer research & treatment 37 29332449
2020 CPEB3-mediated MTDH mRNA translational suppression restrains hepatocellular carcinoma progression. Cell death & disease 33 32968053
2012 Calpain 2 activated through N-methyl-D-aspartic acid receptor signaling cleaves CPEB3 and abrogates CPEB3-repressed translation in neurons. Molecular and cellular biology 33 22711986
2021 Lidocaine Inhibits Hepatocellular Carcinoma Development by Modulating circ_ITCH/miR-421/CPEB3 Axis. Digestive diseases and sciences 30 33433806
2019 miRNA-301b-3p accelerates migration and invasion of high-grade ovarian serous tumor via targeting CPEB3/EGFR axis. Journal of cellular biochemistry 30 30834603
2014 Elevated activation of CaMKIIα in the CPEB3-knockout hippocampus impairs a specific form of NMDAR-dependent synaptic depotentiation. Frontiers in cellular neuroscience 29 25404896
2010 CPEB2, CPEB3 and CPEB4 are coordinately regulated by miRNAs recognizing conserved binding sites in paralog positions of their 3'-UTRs. Nucleic acids research 28 20660482
2020 CPEB3 functions as a tumor suppressor in colorectal cancer via JAK/STAT signaling. Aging 22 33146632
2021 MiR-20b-5p promotes hepatocellular carcinoma cell proliferation, migration and invasion by down-regulating CPEB3. Annals of hepatology 20 33812045
2021 CPEB3 deficiency in mice affect ovarian follicle development and causes premature ovarian insufficiency. Cell death & disease 20 34930897
2020 linc00968 inhibits the tumorigenesis and metastasis of lung adenocarcinoma via serving as a ceRNA against miR-9-5p and increasing CPEB3. Aging 20 33159015
2020 LINC00641 hinders the progression of cervical cancer by targeting miR-378a-3p/CPEB3. The journal of gene medicine 19 32367630
2020 Emotional Stress Induces Structural Plasticity in Bergmann Glial Cells via an AC5-CPEB3-GluA1 Pathway. The Journal of neuroscience : the official journal of the Society for Neuroscience 17 32229518
2020 TRIM11 stimulates the proliferation of gastric cancer through targeting CPEB3/EGFR axis. Journal of B.U.ON. : official journal of the Balkan Union of Oncology 17 33099959
2019 LncRNA SUMO1P3 promotes proliferation and inhibits apoptosis in colorectal cancer by epigenetically silencing CPEB3. Biochemical and biophysical research communications 17 30799082
2018 Effects of Lidocaine-Mediated CPEB3 Upregulation in Human Hepatocellular Carcinoma Cell Proliferation In Vitro. BioMed research international 17 29850575
2022 CPEB3-dependent increase in GluA2 subunits impairs excitatory transmission onto inhibitory interneurons in a mouse model of fragile X. Cell reports 16 35675768
2020 Exploring the F-actin/CPEB3 interaction and its possible role in the molecular mechanism of long-term memory. Proceedings of the National Academy of Sciences of the United States of America 16 32848053
2009 Characterization of the transcripts and protein isoforms for cytoplasmic polyadenylation element binding protein-3 (CPEB3) in the mouse retina. BMC molecular biology 16 20003455
2023 CPEB3 low-complexity motif regulates local protein synthesis via protein-protein interactions in neuronal ribonucleoprotein granules. Proceedings of the National Academy of Sciences of the United States of America 15 36716374
2022 CPEB3 suppresses gastric cancer progression by inhibiting ADAR1-mediated RNA editing via localizing ADAR1 mRNA to P bodies. Oncogene 15 36068334
2021 CPEB3-dowregulated Nr3c1 mRNA translation confers resilience to developing posttraumatic stress disorder-like behavior in fear-conditioned mice. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 15 33941859
2023 MicroRNA-92a-CPEB3 axis protects neurons against inflammatory neurodegeneration. Science advances 14 38000031
2022 Circ_0007624 suppresses the development of esophageal squamous cell carcinoma via targeting miR-224-5p/CPEB3 to inactivate the EGFR/PI3K/AKT signaling. Cellular signalling 14 35998761
2016 Topological Regulation of Synaptic AMPA Receptor Expression by the RNA-Binding Protein CPEB3. Cell reports 14 27681423
2021 MiR-9-5p promotes cell proliferation and migration of hepatocellular carcinoma by targeting CPEB3. Biomarkers in medicine 13 33496636
2020 Role of CPEB3 protein in learning and memory: new insights from synaptic plasticity. Aging 13 32619199
2022 Conformational dynamics in the disordered region of human CPEB3 linked to memory consolidation. BMC biology 12 35658951
2015 NH125 reduces the level of CPEB3, an RNA binding protein, to promote synaptic GluA2 expression. Neuropharmacology 11 25842244
2021 MiR-18a-5p Facilitates Progression of Hepatocellular Carcinoma by Targeting CPEB3. Technology in cancer research & treatment 10 34738854
2020 Cytoplasmic Polyadenylation Element Binding Proteins CPEB1 and CPEB3 Regulate the Translation of FosB and Are Required for Maintaining Addiction-Like Behaviors Induced by Cocaine. Frontiers in cellular neuroscience 10 32742260
2016 CPEB3 Deficiency Elevates TRPV1 Expression in Dorsal Root Ganglia Neurons to Potentiate Thermosensation. PloS one 10 26915043
2022 A structural dynamics model for how CPEB3 binding to SUMO2 can regulate translational control in dendritic spines. PLoS computational biology 9 36346822
2025 MiR-103-3p regulates chondrocyte autophagy, apoptosis, and ECM degradation through the PI3K/Akt/mTOR pathway by targeting CPEB3. Journal of orthopaedic surgery and research 8 40155964
2024 circKDM1A suppresses bladder cancer progression by sponging miR-889-3p/CPEB3 and stabilizing p53 mRNA. iScience 8 38632984
2021 Experimental Resurrection of Ancestral Mammalian CPEB3 Ribozymes Reveals Deep Functional Conservation. Molecular biology and evolution 8 33720319
2021 Mapping the Fibril Core of the Prion Subdomain of the Mammalian CPEB3 that is Involved in Long Term Memory Retention. Journal of molecular biology 8 34081983
2021 MicroRNA-21-5p Reduces Hypoxia/Reoxygenation-Induced Neuronal Cell Damage through Negative Regulation of CPEB3. Analytical cellular pathology (Amsterdam) 8 34900520
2022 CPEB3, an RNA-Binding Protein, Modulates the Behavior of Endometriosis-Derived Stromal Cells via Regulating CXCL12. DNA and cell biology 7 35451884
2022 A miR-9-5p/FOXO1/CPEB3 Feed-Forward Loop Drives the Progression of Hepatocellular Carcinoma. Cells 7 35805200
2020 CPEB3 regulates the proliferation and apoptosis of bovine cumulus cells. Animal science journal = Nihon chikusan Gakkaiho 7 32648330
2023 Phase separation modulates the functional amyloid assembly of human CPEB3. Progress in neurobiology 6 37898314
2022 CPEB3 overexpression caused by miR-106b-5p inhibition inhibits esophageal carcinoma in-vitro progression and metastasis. Anti-cancer drugs 6 35102025
2016 Altered splicing leads to reduced activation of CPEB3 in high-grade gliomas. Oncotarget 6 27256982
2024 miR-351-5p regulation of CPEB3 affecting aluminium-induced learning and memory impairment in SD rats. Environmental pollution (Barking, Essex : 1987) 5 39307336
2016 New Phosphospecific Antibody Reveals Isoform-Specific Phosphorylation of CPEB3 Protein. PloS one 5 26915047
2014 Solution structure and metal ion binding sites of the human CPEB3 ribozyme's P4 domain. Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry 5 24652468
2024 CPEB3 Maintains Developmental Competence of the Oocyte. Cells 4 38786074
2023 Neuralized1-Mediated CPEB3 Ubiquitination in the Spinal Dorsal Horn Contributes to the Pathogenesis of Neuropathic Pain in Rats. ACS chemical neuroscience 4 37644621
2020 Long non-coding RNA MIR22HG inhibits glioma progression by downregulating microRNA-9/CPEB3. Oncology letters 4 33552275
2016 Loss of CPEB3 Upregulates MEGF10 to Impair Mosaic Development of ON Starburst Amacrine Cells. Frontiers in molecular neuroscience 3 27822178
2025 Structural insights into functional regulation of the human CPEB3 prion by an amyloid-forming segment. Structure (London, England : 1993) 2 40480223
2024 New Insights into the Dependence of CPEB3 Ribozyme Cleavage on Mn2+ and Mg2. The journal of physical chemistry letters 2 38427973
2025 CPEB3 can regulate seizure susceptibility by inhibiting the transcriptional activity of STAT3 on NMDARs expression. Molecular medicine (Cambridge, Mass.) 1 39994587
2025 Downregulation of Neuralized1 in the Hippocampal CA1 Through Reducing CPEB3 Ubiquitination Mediates Synaptic Plasticity Impairment and Cognitive Deficits in Neuropathic Pain. Neuroscience bulletin 1 41251936
2026 Modeling the functional impact of CPEB3 and CPEB4 dysregulation in autism: A theoretical-computational framework. Molecular and cellular neurosciences 0 41581680
2026 CPEB3 selectively inhibits α-synuclein aggregation without modulating TDP-43 pathology. FEBS letters 0 41732904
2026 Oncogenic SOX9-TRAIP signaling drives gastric cancer progression by mediating the degradation of the CPEB3-mTORC1 tumor suppressor axis. World journal of surgical oncology 0 41832516
2026 Backbone resonance assignments of CPEB3 [1-120], CPEB3 [186-315], and CPEB3 [400-459]. Biomolecular NMR assignments 0 42213271
2025 Exploring the Potential Interaction between the Functional Prion Protein CPEB3 and the Amyloidogenic Pathogenic Protein Tau. The journal of physical chemistry. B 0 39908090
2025 Backbone resonance assignments of the CPEB3 [101-200] and CPEB3 [294-410]. Biomolecular NMR assignments 0 40156755
2025 Purification tags markedly affect self-aggregation of CPEB3. FEBS letters 0 40525527
2025 miR-21-5p inhibitor enhances the radiosensitivity of human cervical cancer cells via blocking CPEB3-mediated CDK1/cyclin B pathway. Biochemistry and biophysics reports 0 40746848
2025 Exploring the Structural Order of Condensates Formed by the PRD2 Domain of Mouse CPEB3. ACS chemical neuroscience 0 40762714
2017 The 5'-AG5 CC-3' Fragment from the Human CPEB3 Ribozyme Forms an Ultrastable Parallel RNA G-Quadruplex. Chembiochem : a European journal of chemical biology 0 28296179

Missed literature

Know a paper Affinage missed for CPEB3? Flag it for the maintainers and the community.

No submissions yet.