Affinage

CPEB2

Cytoplasmic polyadenylation element-binding protein 2 · UniProt Q7Z5Q1

Length
589 aa
Mass
64.9 kDa
Annotated
2026-06-09
37 papers in source corpus 23 papers cited in narrative 23 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CPEB2 is a sequence-specific cytoplasmic RNA-binding protein that uses tandem RNA recognition motifs and a C-terminal ZZ zinc-finger domain to bind cytoplasmic polyadenylation element (CPE) and U-rich motifs in target mRNA 3'-UTRs, thereby controlling translation and stability of selected transcripts in a tissue- and signal-dependent manner (PMID:12672660, PMID:34362680, PMID:31616934). As a translational repressor, CPEB2 binds eEF2 and reduces eEF2/ribosome-triggered GTP hydrolysis to slow peptide elongation, a mechanism that keeps HIF-1α mRNA translationally silent under normoxia; under oxidative stress CPEB2 dissociates from HIF-1α mRNA to permit rapid HIF-1α synthesis, and this switch is gated by NPGPx (GPx7), which forms an intermolecular disulfide bond with CPEB2 (PMID:22157746, PMID:26446990, PMID:31616934). In other contexts CPEB2 acts as a translational activator, driving synthesis of GRASP1, VGLUT2/Slc17a6, Ucp1L, PRDM16, PDGFRα, and ANGPTL3 to support synaptic plasticity, brown adipose thermogenesis and cell-fate maintenance, and alveologenesis (PMID:29141213, PMID:38992696, PMID:30177570, PMID:39305947, PMID:32295602, PMID:41219382). CPEB2 also governs mRNA stability and poly(A)-tail length of targets including p53, p21/CDKN1A, ARPC5, SRSF5, TJP1, and SSTR3, placing it in feedback circuits with p53 and in control of tight-junction assembly and epithelial behavior (PMID:34362680, PMID:38158431, PMID:37231521, PMID:36064747, PMID:35133290, PMID:38648900). Across loss-of-function mouse models, CPEB2 is required for hippocampal LTP and memory, parasympathetic ChAT regulation and airway tone, brown-fat thermogenesis, and alveolar septation (PMID:29141213, PMID:27810937, PMID:30177570, PMID:32295602). CPEB2 abundance is itself regulated post-transcriptionally by miR-92/miR-26 and by m6A methylation via METTL3/IGF2BP3 (PMID:20660482, PMID:36064747).

Mechanistic history

Synthesis pass · year-by-year structured walk · 23 steps
  1. 2003 Medium

    Established the basic biochemical identity of CPEB2 as an RNA-binding protein, defining its domains, ligand preference, and compartment before any functional target was known.

    Evidence RNA-binding (poly(U)) assay, transfection localization, and expression profiling in mouse spermatogenesis

    PMID:12672660

    Open questions at the time
    • No specific physiological target mRNA identified
    • Cytoplasmic role inferred from expression, not functional rescue
  2. 2010 Medium

    Showed how CPEB2 levels themselves are controlled, placing the CPEB2 subfamily under shared miRNA regulation.

    Evidence Reporter mutagenesis with miR-92/miR-26 overexpression and depletion plus endogenous mRNA measurement

    PMID:20660482

    Open questions at the time
    • Does not address CPEB2 protein activity, only transcript abundance
    • Functional consequence for downstream targets not tested
  3. 2011 High

    Resolved the molecular mechanism of CPEB2-mediated repression, showing it acts at translation elongation via eEF2 rather than only at polyadenylation.

    Evidence Co-IP, in vitro eEF2 GTP hydrolysis assay, in vivo reporter and RIP for HIF-1α mRNA

    PMID:22157746

    Open questions at the time
    • Whether elongation control generalizes to non-HIF-1α targets untested
    • Structural basis of the eEF2 interaction not defined
  4. 2015 High

    Identified the redox switch that couples oxidative stress to CPEB2 release from HIF-1α mRNA, explaining stress-induced HIF-1α induction.

    Evidence Non-reducing co-IP for disulfide bond, RIP, and translation reporter in NPGPx-proficient/deficient cells

    PMID:26446990

    Open questions at the time
    • Cysteine residues mediating the disulfide not mapped
    • Generality of redox gating to other CPEB2 targets unknown
  5. 2016 High

    Demonstrated an in vivo translational-activation role distinct from repression, linking CPEB2 to a defined neural circuit and physiological output.

    Evidence Global and cholinergic-neuron-specific KO mice, plethysmography, ChAT Western blot, pharmacological rescue

    PMID:27810937

    Open questions at the time
    • Direct CPEB2 binding to ChAT mRNA not biochemically shown here
    • Mechanism switching CPEB2 from repressor to activator unclear
  6. 2017 High

    Connected CPEB2 to synaptic plasticity by identifying GRASP1 as an activated target controlling AMPA receptor surface expression and LTP.

    Evidence Forebrain conditional KO, LTP electrophysiology, AMPAR surface biotinylation, polysome profiling, AAV rescue with CPEB2 and GRASP1

    PMID:29141213

    Open questions at the time
    • CPE-dependence of GRASP1 activation not detailed
    • Signal triggering activation in neurons not defined
  7. 2017 Medium

    Revealed that splice isoforms diverge functionally, with the exon-4-containing CPEB2B driving translational activation of TWIST1/HIF-1α and metastasis.

    Evidence Isoform-specific siRNA, translatome NGS, anoikis and in vivo metastasis assays in TNBC cells

    PMID:28904175

    Open questions at the time
    • Structural basis for exon-4 conferring activation unknown
    • Single cancer-cell context
  8. 2018 High

    Showed signal-dependent, 3'-UTR-isoform-selective activation, with CPEB2 driving long-UTR Ucp1L translation downstream of β3-adrenergic signaling for thermogenesis.

    Evidence CPEB2-KO and Ucp1S-only mice, thermogenesis measurement, reporter assay, ectopic CPEB2 rescue

    PMID:30177570

    Open questions at the time
    • How CPEB2 discriminates long vs short Ucp1 UTR mechanistically not resolved
    • Direct binding site on Ucp1L not mapped here
  9. 2019 Medium

    Extended CPEB2 to mRNA-stability control and tight-junction assembly in early embryos via TJP1 transcript regulation.

    Evidence dsRNA knockdown in porcine embryos, TJ-protein immunocytochemistry, qRT-PCR, Western blot

    PMID:30145997

    Open questions at the time
    • Direct CPEB2 binding to TJP1 mRNA not shown in this study
    • Mechanism of stability control undefined
  10. 2019 Medium

    Defined a tumor-suppressor function for CPEB2 isoform A through translational upregulation of p53 in mammary epithelial cells.

    Evidence CRISPR KO and siRNA in MCF10A, polysome profiling, oncogenicity assays, xenograft

    PMID:31185986

    Open questions at the time
    • Direct CPE binding to p53 mRNA established only later
    • Contrast with pro-tumor isoform B not mechanistically reconciled
  11. 2020 Medium

    Established direct CPE-dependent binding and repression of HIF-1α in trophoblasts, embedding CPEB2 in a miR-210 feedback loop controlling syncytialization.

    Evidence RIP, CPE-mutagenesis luciferase reporter, syncytialization assay, miR-210 inhibition

    PMID:31616934

    Open questions at the time
    • Single cell-type context
    • Relationship to eEF2-mediated repression mechanism not addressed
  12. 2020 High

    Linked CPEB2 to lung development via PDGFRα translation in myofibroblast progenitors, with oxidative disruption recapitulating the elongation-control theme.

    Evidence CPEB2-KO mice, RIP, reporter assay, histology, primary MYF rescue, plethysmography

    PMID:32295602

    Open questions at the time
    • Whether PDGFRα activation uses elongation vs polyadenylation control unspecified
    • H2O2 sensitivity mechanism vs NPGPx link not directly tested
  13. 2021 Medium

    Mapped the domain requirement (RRM/ZF) for direct p53 mRNA binding and defined a p53–CPEB2 negative feedback loop in renal cancer.

    Evidence RIP with domain mutagenesis, mRNA stability and translation reporter assays, proliferation/migration assays

    PMID:34362680

    Open questions at the time
    • Reconciliation with CPEB2 activating p53 in mammary cells unresolved
    • Context-dependence of repression vs activation undefined
  14. 2022 Medium

    Showed CPEB2 stabilizes SRSF5 mRNA to shape splicing and barrier integrity, and identified m6A/METTL3/IGF2BP3 control of CPEB2 mRNA itself.

    Evidence RIP, m6A assay, splicing analysis, in vitro BTB model, glioblastoma xenograft knockdown

    PMID:36064747

    Open questions at the time
    • Direct effect on splicing vs indirect via SRSF5 not separated mechanistically
    • m6A regulation studied only in glioma endothelium
  15. 2022 Medium

    Demonstrated CPEB2 controls subcellular Tjp1 mRNA localization and poly(A)-tail length in embryos, linking it to spatial translation and tight-junction assembly.

    Evidence Knockdown in mouse embryos, FISH mRNA localization, poly(A) tail assay, blastocyst formation/transfer

    PMID:35133290

    Open questions at the time
    • Transport machinery partnering with CPEB2 unidentified
    • Link between poly(A) change and localization mechanistically open
  16. 2023 Medium

    Added cell-cycle control to the CPEB2 repertoire through stabilization of p21/CDKN1A mRNA driving G1 arrest in glioma.

    Evidence Overexpression/knockdown, actinomycin D stability chase, flow cytometry, xenograft

    PMID:38158431

    Open questions at the time
    • Direct binding to p21 mRNA not shown here
    • Relation to CPEB2 oncogenic roles elsewhere unresolved
  17. 2023 Medium

    Identified ARPC5 mRNA as a CPEB2-stabilized target supporting myeloma proliferation and angiogenesis.

    Evidence RIP, actinomycin D stability assay, FISH co-localization, rescue by ARPC5

    PMID:37231521

    Open questions at the time
    • Binding site within ARPC5 mRNA not mapped
    • Single cancer context
  18. 2024 High

    Established axonal, presynaptic translational activation of VGLUT2/Slc17a6 by CPEB2 as a requirement for protein-synthesis-dependent LTP.

    Evidence Presynaptic-specific conditional KO, RIP-seq, LTP electrophysiology, synaptosome biochemistry, microfluidic axon culture, reporter

    PMID:38992696

    Open questions at the time
    • Local signal triggering axonal CPEB2 activation undefined
    • CPE-dependence of Slc17a6 binding not detailed
  19. 2024 High

    Showed CPEB2 maintains brown-fat identity by activating Prdm16 translation, with loss causing a fate shift toward muscle gene programs and weight gain.

    Evidence Global and adipose-specific KO, RNA-seq, polysome profiling, reporter, AAV PRDM16 rescue

    PMID:39305947

    Open questions at the time
    • Direct CPEB2 binding site on Prdm16 mRNA not mapped
    • Signal coupling to activation unspecified
  20. 2024 Medium

    Demonstrated CPE-dependent repression of SSTR3 via poly(A)-tail shortening in trophoblasts, connecting CPEB2 to preeclampsia-relevant cell behavior.

    Evidence RIP, dual-luciferase reporter, poly(A) tail PCR, rat PE model with AAV overexpression

    PMID:38648900

    Open questions at the time
    • Reconciliation of repressor activity here with activator roles elsewhere not addressed
    • Mechanism choosing deadenylation vs activation undefined
  21. 2025 Medium

    Added ANGPTL3 as a CPEB2-activated target in podocytes, with reciprocal ANGPTL3-driven stabilization of CPEB2 forming a feed-forward injury loop.

    Evidence RIP, polysome profiling, in vivo AAV9-shCPEB2 knockdown, mRNA stability assay

    PMID:41219382

    Open questions at the time
    • Direct CPE site on ANGPTL3 mRNA not mapped
    • Single disease model
  22. 2025 Medium

    Defined the C-terminal ZZ domain as the necessary and sufficient module for translational repression and co-repressor recruitment, conserved from Drosophila ORB2 to human CPEB2.

    Evidence Tethered reporter repression in S2 cells, CRISPR ZZ deletion, RIP, ribosome profiling, interaction assays (preprint)

    PMID:bio_10.1101_2025.07.10.664187

    Open questions at the time
    • Preprint, not peer-reviewed
    • Cup-complex equivalent in mammalian CPEB2 repression not confirmed
  23. 2025 Medium

    Showed the ZZ domain also governs CPEB2-ortholog localization and co-factor recruitment in spermatids, linking the repressive module to spatial organization and fertility.

    Evidence CRISPR ZZ deletion in Drosophila, immunofluorescence localization, fertility and individualization-complex assays (preprint)

    PMID:bio_10.1101_2025.08.22.671863

    Open questions at the time
    • Preprint, not peer-reviewed
    • Mammalian relevance of spermatid localization role untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • What determines whether CPEB2 represses or activates a given target, and how its domains, isoforms, redox/m6A modifications, and co-factor complexes integrate to select between elongation control, polyadenylation, and mRNA stabilization, remains unresolved.
  • No unified model reconciling repressor vs activator outputs across tissues
  • Mammalian co-repressor complex equivalent to Drosophila Cup not identified
  • No structural model of CPE/eEF2/ZZ interactions

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003723 RNA binding 9 GO:0045182 translation regulator activity 7 GO:0098772 molecular function regulator activity 1
Localization
GO:0005829 cytosol 2
Pathway
R-HSA-392499 Metabolism of proteins 5 R-HSA-8953854 Metabolism of RNA 5 R-HSA-8953897 Cellular responses to stimuli 3
Partners
EEF2NPGPX

Evidence

Reading pass · 23 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2011 CPEB2 interacts directly with elongation factor eEF2 to reduce eEF2/ribosome-triggered GTP hydrolysis in vitro, thereby slowing peptide elongation of CPEB2-bound RNA in vivo. This mechanism represses HIF-1α mRNA translation under normoxia; under oxidative stress, CPEB2 dissociates from HIF-1α mRNA, enabling rapid HIF-1α synthesis. Co-immunoprecipitation, in vitro GTP hydrolysis assay, in vivo translation reporter assay, RNA-immunoprecipitation The EMBO journal High 22157746
2003 CPEB2 contains two RNA recognition motifs and a zinc-finger (ZZ) domain, preferentially binds poly(U) RNA, and localizes to the cytoplasm in transfected HeLa cells. It is expressed postmeiotically in mouse spermatogenesis, consistent with a role in translational regulation of stored mRNAs in haploid spermatids. RNA-binding assay (poly(U) preference), subcellular localization by transfection/imaging, RT-PCR expression profiling, chromosome mapping Biology of reproduction Medium 12672660
2015 NPGPx (GPx7) forms an intermolecular disulfide bond with CPEB2 under oxidative stress conditions. In NPGPx-proficient cells, high oxidative stress disrupts this bond and compromises CPEB2 association with HIF-1α mRNA, leading to elevated HIF-1α translation. NPGPx-deficient cells show increased basal HIF-1α translation with impaired stress-induced induction. Disulfide bond detection (co-immunoprecipitation under non-reducing conditions), RNA-immunoprecipitation, translation reporter assay Nucleic acids research High 26446990
2016 CPEB2 knockout mice show upregulated translation of choline acetyltransferase (ChAT) mRNA specifically in the dorsal motor nucleus of vagus, leading to hyperactivated parasympathetic (cholinergic) signaling, elevated pulmonary acetylcholine, increased phospho-myosin light chain 2 in bronchial smooth muscles, and bronchoconstriction. Cholinergic neuron-specific CPEB2 deletion recapitulates apnea and airway hyper-reactivity. Global and conditional (cholinergic neuron-specific) CPEB2 knockout mice, whole-body plethysmography, Western blotting (ChAT protein levels), acetylcholine measurement, anticholinergic bronchodilator rescue The Journal of neuroscience High 27810937
2017 CPEB2 activates GRASP1 mRNA translation in forebrain neurons. CPEB2 conditional knockout mice show reduced surface (but not total) AMPA receptor expression and impaired long-term potentiation (LTP) in the Schaffer collateral–CA1 pathway. Ectopic expression of CPEB2 or GRASP1 in CA1 of KO mice rescues LTP and spatial memory. Forebrain-restricted conditional knockout mice, electrophysiology (LTP), AMPA receptor surface biotinylation, polysomal profiling/translation assay, stereotaxic AAV rescue Cell reports High 29141213
2017 The CPEB2B splice isoform (containing exon 4) functions as a translational activator of TWIST1 and HIF-1α mRNAs and promotes EMT, anoikis resistance, and metastasis in triple-negative breast cancer cells. Conversely, CPEB2A (lacking exon 4) does not drive these pathways; specific knockdown of CPEB2B inhibits EMT and hypoxic-response gene expression. Isoform-specific siRNA knockdown, next-generation sequencing of translatome, Western blotting for HIF-1α and TWIST1, anoikis assay, in vivo metastasis assay The Journal of biological chemistry Medium 28904175
2018 CPEB2 is required for β3 adrenergic receptor signaling-induced translation of the long 3'-UTR Ucp1 mRNA (Ucp1L) in brown adipose tissue. CPEB2-knockout mice show reduced UCP1 protein levels and impaired thermogenesis, rescued by ectopic CPEB2 expression. Mice expressing only short Ucp1 (Ucp1S) have 60% less UCP1 protein and impaired thermogenesis. CPEB2 and Ucp1L-specific knockout mice, Western blotting, thermogenesis measurements, ectopic CPEB2 rescue, translation reporter assay The EMBO journal High 30177570
2019 CPEB2 depletion in porcine embryos impairs tight-junction (TJ) assembly at the morula stage. TJ-associated proteins TJP1, CXADR, and occludin are not properly localized to the apical membrane despite normal transcript levels. CPEB2 mediates stability of TJP1 mRNA bearing its 3'-UTR, as evidenced by reduced levels of 3'-UTR-containing TJP1 transcripts upon CPEB2 knockdown. dsRNA-mediated CPEB2 knockdown in porcine embryos, immunocytochemistry for TJ protein localization, qRT-PCR, Western blotting Reproduction, fertility, and development Medium 30145997
2019 CPEB2 (isoform A) acts as a tumor suppressor in mammary epithelial cells. CPEB2 knockout (CRISPR) in MCF10A cells causes increased proliferation, migration, invasion, EMT, and stem-like cell phenotype. CPEB2 was shown by polysome profiling to translationally upregulate p53 protein, identifying p53 as a novel CPEB2 translational target. CRISPR/Cas9 knockout, siRNA knockdown, polysomal profiling, in vitro oncogenicity assays, in vivo xenograft/metastasis assay BMC cancer Medium 31185986
2020 CPEB2 directly binds the cytoplasmic polyadenylation element (CPE) site in the 3'-UTR of HIF-1α mRNA in human trophoblasts and inhibits HIF-1α translation. Under hypoxia, miR-210 targets CPEB2, releasing HIF-1α translational repression and creating a positive feedback loop. CPEB2 is required for trophoblast syncytialization; miR-210-mediated suppression of CPEB2 impairs syncytialization and is rescued by CPEB2 overexpression. RNA immunoprecipitation, luciferase reporter assay (CPE site mutagenesis), trophoblast syncytialization assay, miR-210 inhibitor experiments, Western blotting Biology of reproduction Medium 31616934
2020 CPEB2 promotes translation of PDGFRα mRNA in alveolar myofibroblast (MYF) progenitors, supporting their proliferation during pulmonary alveologenesis. CPEB2-knockout mice develop emphysema-like pathology with simplified alveolar structure, reduced MYF proliferation, abnormal elastin deposition, and failure of alveolar septum formation. H2O2 (hyperoxia-mimetic) disrupts CPEB2-mediated PDGFRα translation, and KO MYF proliferation defects are rescued by ectopic CPEB2. CPEB2-knockout mice, RNA immunoprecipitation, luciferase reporter assay, Western blotting, histology, ectopic CPEB2 rescue in primary MYF culture, plethysmography Journal of biomedical science High 32295602
2021 CPEB2 binds CPE sites in the p53 mRNA 3'-UTR via its RNA recognition motif and zinc finger domains, decreasing p53 mRNA stability and translation. p53 in turn transcriptionally activates CPEB2 expression, establishing a negative feedback loop. CPEB2 overexpression promotes renal cancer cell proliferation and migration in a partially p53-dependent manner. RNA immunoprecipitation, domain mutagenesis (RRM/ZF deletion), mRNA stability assay, translation reporter assay, cell proliferation and migration assays Journal of genetics and genomics Medium 34362680
2022 CPEB2 binds SRSF5 mRNA and increases its stability, promoting ETS1 exon inclusion (producing P51-ETS1 isoform), which transcriptionally upregulates tight junction proteins ZO-1, occludin, and claudin-5 to regulate blood-tumor barrier permeability. CPEB2 mRNA is itself stabilized via m6A methylation by METTL3/IGF2BP3 in glioma endothelial cells. RNA immunoprecipitation, m6A methylation assay, splicing analysis, Western blotting, in vitro BTB model, in vivo glioblastoma xenograft with knockdown Communications biology Medium 36064747
2022 CPEB2 mediates subcellular translocation of Tjp1 mRNA from the nucleus to the apical membrane in mouse morula outer cells, and regulates Tjp1 mRNA poly(A) tail length. CPEB2 knockdown abolishes apical Tjp1 mRNA localization, impairs poly(A) tail heterogeneity, reduces blastocyst formation, and disrupts tight junction assembly. CPEB2 knockdown in mouse embryos, fluorescence in situ hybridization for mRNA localization, poly(A) tail length assay, blastocyst formation and embryo transfer assay Reproduction (Cambridge, England) Medium 35133290
2023 CPEB2 increases p21 (CDKN1A) mRNA stability in glioma cells, causing G1 cell cycle arrest and reduced proliferation. CPEB2 overexpression or knockdown correspondingly alters p21 levels and cell proliferation/apoptosis in vitro and tumor growth in vivo. CPEB2 overexpression and knockdown, mRNA stability assay (actinomycin D chase), flow cytometry for cell cycle, in vivo xenograft Scientific reports Medium 38158431
2023 CPEB2 directly binds ARPC5 mRNA via RNA immunoprecipitation and promotes ARPC5 mRNA stability in multiple myeloma cells. CPEB2 and ARPC5 co-localize in the cytoplasm. CPEB2 depletion reduces MM cell proliferation and angiogenesis, and ARPC5 overexpression rescues these effects. RNA immunoprecipitation, actinomycin D mRNA stability assay, fluorescence in situ hybridization (co-localization), Western blotting, cell functional assays Journal of orthopaedic surgery and research Medium 37231521
2024 CPEB2 activates translation of Slc17a6 mRNA (encoding VGLUT2) in axons of glutamatergic neurons. Presynaptic-specific ablation of CPEB2 in VGLUT2-dominated temporoammonic afferents attenuates protein synthesis-dependent LTP. CPEB2 deficiency or cycloheximide treatment reduces the releasable pool of VGLUT2-containing synaptic vesicles and impairs axonal Slc17a6 translation. Conditional (glutamatergic neuron-specific and presynaptic-specific) CPEB2 knockout, RNA immunoprecipitation coupled with transcriptomics, electrophysiology (LTP), synaptosome biochemistry, microfluidic axotomized neuron culture, luciferase reporter assay, stereotaxic AAV-Cre delivery Journal of biomedical science High 38992696
2024 CPEB2 activates translation of Prdm16 mRNA in brown adipose tissue. CPEB2-knockout mice show upregulated muscle-development gene expression in BAT (indicating cell fate shift), reduced PRDM16 protein without corresponding mRNA changes (polysomal profiling), and increased weight gain. AAV-mediated PRDM16 expression in CPEB2-deficient BAT restores gene expression and reduces weight gain. Global CPEB2 knockout, adipose-specific conditional knockout, RNA sequencing, polysomal profiling, luciferase reporter assay, AAV rescue in BAT Molecular metabolism High 39305947
2024 CPEB2 binds the CPE site in the 3'-UTR of SSTR3 mRNA and suppresses SSTR3 translation by reducing poly(A) tail length, as confirmed by RIP assay, dual-luciferase reporter, and PCR poly(A) tail assay. Reduced SSTR3 expression downstream of CPEB2 promotes trophoblast cell proliferation, migration, invasion, and EMT. RNA immunoprecipitation (RIP), dual-luciferase reporter assay, poly(A) tail PCR assay, Western blotting, cell functional assays, in vivo rat PE model with AAV overexpression Biochimica et biophysica acta. Molecular basis of disease Medium 38648900
2010 miR-92 and miR-26 bind conserved sites in the 3'-UTRs of CPEB2, CPEB3, and CPEB4 at paralogous positions, co-regulating their transcript levels. Mutagenesis of miRNA-binding sites in reporter constructs combined with miRNA overexpression and depletion confirmed that both miRNAs reduce luciferase reporter activity and endogenous CPEB2 subfamily mRNA levels. Reporter assay with miRNA-binding site mutagenesis, miRNA overexpression and depletion, endogenous mRNA measurement by qRT-PCR Nucleic acids research Medium 20660482
2025 CPEB2 directly binds the 3'-UTR of ANGPTL3 mRNA and promotes its recruitment to translation initiation complexes, increasing ANGPTL3 transcript abundance in high-translating polysomes (polysomal profiling). This translational upregulation of ANGPTL3 by CPEB2 drives podocyte injury. Conversely, ANGPTL3 signaling increases CPEB2 mRNA stability. AAV9-shCPEB2 in vivo reduces ANGPTL3, mitigates albuminuria, and attenuates histopathological injury. RNA immunoprecipitation, polysomal profiling, Western blotting, in vivo AAV9-mediated CPEB2 knockdown, mRNA stability assay Scientific reports Medium 41219382
2025 Drosophila ORB2 (ortholog of human CPEB2-4 subfamily) binds hundreds of maternally provided mRNAs enriched in U-rich 3'-UTR motifs and represses their translation during the maternal-to-zygotic transition via its C-terminal ZZ (zinc-binding) domain. The ZZ domain is necessary and sufficient for translational repression when tethered to a reporter, and human CPEB2 (but not CPEB1) similarly represses translation when tethered. The ZZ domain interacts with the Cup repressive complex; deletion of ZZ domain disrupts these interactions and causes derepression of ORB2-specific (but not SMG co-bound) target mRNAs. Tethered reporter repression assay in S2 cells, endogenous ZZ domain deletion (CRISPR), RNA immunoprecipitation, translatome profiling (ribosome profiling), protein interaction assays bioRxivpreprint Medium bio_10.1101_2025.07.10.664187
2025 The ZZ domain of Drosophila ORB2 (CPEB2 ortholog) is required for its localization to the distal tip of spermatids. Deletion of the ZZ domain causes mislocalization of ORB2 and of co-factors ORB, IMP, and SOTI; loss of the SOTI-dependent Cleaved Caspase 3 gradient; defective individualization complexes; and male sterility with absence of mature sperm. Endogenous ZZ domain deletion (CRISPR), immunofluorescence localization, fertility assay, immunostaining for individualization complex markers bioRxivpreprint Medium bio_10.1101_2025.08.22.671863

Source papers

Stage 0 corpus · 37 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2017 TUG1 mediates methotrexate resistance in colorectal cancer via miR-186/CPEB2 axis. Biochemical and biophysical research communications 88 28302487
2017 LncRNA CCAT1 modulates the sensitivity of paclitaxel in nasopharynx cancers cells via miR-181a/CPEB2 axis. Cell cycle (Georgetown, Tex.) 69 28358263
2011 CPEB2-eEF2 interaction impedes HIF-1α RNA translation. The EMBO journal 63 22157746
2003 CPEB2, a novel putative translational regulator in mouse haploid germ cells. Biology of reproduction 46 12672660
2017 Identification of microRNA 885-5p as a novel regulator of tumor metastasis by targeting CPEB2 in colorectal cancer. Oncotarget 36 28460469
2017 CPEB2 Activates GRASP1 mRNA Translation and Promotes AMPA Receptor Surface Expression, Long-Term Potentiation, and Memory. Cell reports 32 29141213
2022 CPEB2 m6A methylation regulates blood-tumor barrier permeability by regulating splicing factor SRSF5 stability. Communications biology 30 36064747
2018 CPEB2-dependent translation of long 3'-UTR Ucp1 mRNA promotes thermogenesis in brown adipose tissue. The EMBO journal 28 30177570
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 A positive feedback self-regulatory loop between miR-210 and HIF-1α mediated by CPEB2 is involved in trophoblast syncytialization: implication of trophoblast malfunction in preeclampsia†. Biology of reproduction 24 31616934
2019 Tumor suppressor role of cytoplasmic polyadenylation element binding protein 2 (CPEB2) in human mammary epithelial cells. BMC cancer 21 31185986
2020 The RNA binding protein CPEB2 regulates hormone sensing in mammary gland development and luminal breast cancer. Science advances 20 32440535
2021 STAT1 mediated long non-coding RNA LINC00504 influences radio-sensitivity of breast cancer via binding to TAF15 and stabilizing CPEB2 expression. Cancer biology & therapy 18 34908514
2015 NPGPx modulates CPEB2-controlled HIF-1α RNA translation in response to oxidative stress. Nucleic acids research 18 26446990
2017 Splice variants of cytosolic polyadenylation element-binding protein 2 (CPEB2) differentially regulate pathways linked to cancer metastasis. The Journal of biological chemistry 16 28904175
2016 Deficiency of CPEB2-Confined Choline Acetyltransferase Expression in the Dorsal Motor Nucleus of Vagus Causes Hyperactivated Parasympathetic Signaling-Associated Bronchoconstriction. The Journal of neuroscience : the official journal of the Society for Neuroscience 16 27810937
2023 CPEB2 inhibit cell proliferation through upregulating p21 mRNA stability in glioma. Scientific reports 13 38158431
2020 Osthole inhibited cell proliferation and induced cell apoptosis through decreasing CPEB2 expression via up-regulating miR-424 in endometrial carcinoma. Journal of receptor and signal transduction research 13 31971049
2018 CPEB2 Is Necessary for Proper Porcine Meiotic Maturation and Embryonic Development. International journal of molecular sciences 13 30322039
2021 A p53/CPEB2 negative feedback loop regulates renal cancer cell proliferation and migration. Journal of genetics and genomics = Yi chuan xue bao 11 34362680
2020 CPEB2-activated PDGFRα mRNA translation contributes to myofibroblast proliferation and pulmonary alveologenesis. Journal of biomedical science 9 32295602
2023 CPEB2 enhances cell growth and angiogenesis by upregulating ARPC5 mRNA stability in multiple myeloma. Journal of orthopaedic surgery and research 8 37231521
2024 CPEB2-activated axonal translation of VGLUT2 mRNA promotes glutamatergic transmission and presynaptic plasticity. Journal of biomedical science 7 38992696
2023 CPEB2 Suppresses Hepatocellular Carcinoma Epithelial-Mesenchymal Transition and Metastasis through Regulating the HIF-1α/miR-210-3p/CPEB2 Axis. Pharmaceutics 7 37514073
2024 CPEB2-activated Prdm16 translation promotes brown adipocyte function and prevents obesity. Molecular metabolism 5 39305947
2023 MIR-147B Regulated Proliferation and Apoptosis of Gastric Cancer Cells by Targeting CPEB2 Via the PTEN Pathway. Balkan journal of medical genetics : BJMG 5 36880039
2019 Cytoplasmic polyadenylation element binding protein 2 (CPEB2) is required for tight-junction assembly for establishment of porcine trophectoderm epithelium. Reproduction, fertility, and development 3 30145997
2025 LncRNA CCAT1 decreases the sensitivity to doxorubicin in lung cancer cells by regulating miR-181a/CPEB2 axis. Medical oncology (Northwood, London, England) 2 40089944
2022 Regulation of Tjp1 mRNA by CPEB2 for tight junction assembly in mouse blastocyst. Reproduction (Cambridge, England) 2 35133290
2025 Human Mesenchymal Stem Cell Derived Exosomes Endowed with miR-13474 as a Therapeutic Delivery Vehicle for Diabetic Wound Healing by Targeting the CPEB2/TWIST1 Axis. ACS applied bio materials 1 41092373
2024 CPEB2 inhibits preeclampsia progression by regulating SSTR3 translation through polyadenylation. Biochimica et biophysica acta. Molecular basis of disease 1 38648900
2019 Corrigendum to: Cytoplasmic polyadenylation element binding protein 2 (CPEB2) is required for tight-junction assembly for establishment of porcine trophectoderm epithelium. Reproduction, fertility, and development 1 31039976
2026 Spitz Melanocytoma With a Novel CPEB2::MAP3K2 Rearrangement: A Case Report. Journal of cutaneous pathology 0 41924997
2025 Identification of lncRNA biomarkers for keloid diagnosis and functional characterization of CPEB2-AS1. Burns : journal of the International Society for Burn Injuries 0 40101610
2025 A Maternal Gene Regulator CPEB2 Is Involved in Mating-Induced Egg Maturation in the Cnaphalocrocis medinalis. Insects 0 40725298
2025 miR-363-5p regulates liver disease via the MAPK/ERK signaling pathway by targeting CPEB2 in chicken. Poultry science 0 40803288
2025 A CPEB2/ANGPTL3 feedback loop promotes the progression of podocyte injury in nephrotic syndrome. Scientific reports 0 41219382

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