Affinage

NREP

Neuronal regeneration-related protein · UniProt Q16612

Length
68 aa
Mass
7.9 kDa
Annotated
2026-06-10
62 papers in source corpus 29 papers cited in narrative 29 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

NREP (P311) is a small, intrinsically disordered, rapidly proteasome-degraded RNA-binding protein that acts as the central translational activator of the TGF-β system and, through it, governs myofibroblast biology, fibrosis, and cell migration (PMID:10660586, PMID:24091331, PMID:25336651). Mechanistically, NREP directly binds the 5'UTR mRNAs of TGF-β1, TGF-β2, and TGF-β3 through an RNA-recognition-motif-like element and recruits the translation initiation machinery by directly engaging eIF3 subunit b (eIF3b, Kd ≈ 1.26 µM) via a defined 11-residue motif, thereby stimulating TGF-β translation without altering TGF-β mRNA levels; disrupting the NREP–eIF3b interaction abolishes this output (PMID:25336651). This translational axis is physiologically decisive: NREP-null mice are hypotensive with impaired vascular smooth muscle contractility and reduced TGF-β protein, both fully rescued by exogenous TGF-β, while transgenic mice are hypertensive (PMID:24091331). The same axis drives fibrosis across organs—renal, pulmonary, dermal—operating through TGF-β/Smad2/3 signaling, upregulation of TGF-β receptors, and conversion of fibroblasts and epidermal stem cells into α-SMA-positive myofibroblast-like cells (PMID:26616407, PMID:27906099, PMID:30230348, PMID:37469904). Independent of translation, NREP promotes cell migration downstream of β1 integrin by activating Rac1 and RhoA GTPases (and RalA in ameboid migration), with stability governed by serine phosphorylation at S59 near its PEST domain and an interaction with Filamin A at the cell periphery (PMID:16229809, PMID:16934802, PMID:27927130). NREP expression is itself tightly controlled—transcriptionally activated by HIF-1α under hypoxia and by TGF-β-induced Meox1, and post-transcriptionally repressed by miR-7a-5p targeting its 3'UTR and enhanced by YTHDF1-mediated m6A-dependent translation (PMID:32411720, PMID:32539181, PMID:42153780, PMID:38697993). Beyond fibrosis, NREP is required in vivo for normal learning, memory, and the affective component of pain (PMID:18616608, PMID:18549486).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 2000 Medium

    Established NREP/P311 as a short-lived protein, defining proteostatic control as a built-in regulatory feature before any function was known.

    Evidence Lactacystin treatment and half-life measurement in transformed cells

    PMID:10660586

    Open questions at the time
    • Identity of the metalloprotease was not determined
    • Functional consequence of rapid turnover unknown at this stage
  2. 2001 Medium

    First functional role: linked NREP to glioma cell migration and focal-adhesion localization, framing it as a motility regulator.

    Evidence Antisense knockdown, integrin activation assays, immunochemistry in invasive glioma cells

    PMID:11358844

    Open questions at the time
    • Molecular mechanism connecting NREP to adhesion machinery not defined
    • No interacting partner identified
  3. 2002 High

    Showed NREP drives a myofibroblast phenotype while paradoxically suppressing TGF-β1, suggesting a complex, isoform-selective relationship to TGF-β rather than simple agonism.

    Evidence Gain-of-function transfection in NIH3T3 and C3H10T1/2 fibroblasts with rescue experiments

    PMID:12417574

    Open questions at the time
    • Reconciling phenotype with TGF-β1 suppression unresolved at the time
    • No molecular mechanism for TGF-β regulation
  4. 2004 High

    Provided a physical handle on TGF-β control by showing NREP binds the latency-associated protein of TGF-β1/β2 and that its PEST domain mediates the effect, while implicating reduced Smad3 autoinduction.

    Evidence Yeast two-hybrid, Co-IP, PEST-deletion mutagenesis, Smad3 reporter

    PMID:14985127

    Open questions at the time
    • TGF-β3 not bound, leaving isoform selectivity unexplained
    • Did not resolve whether regulation was transcriptional, translational, or via LAP
  5. 2004 Medium

    Extended NREP to the nervous system, showing it promotes neurite outgrowth and PC12 differentiation in a Rho-kinase-sensitive manner, linking it to cytoskeletal/neuronal programs.

    Evidence Adenoviral overexpression, PC12 differentiation, Rho kinase inhibition, facial nerve axotomy model

    PMID:15485502

    Open questions at the time
    • Direct molecular target in neurons not identified
    • Relationship to TGF-β axis in neurons unaddressed
  6. 2005 High

    Defined the migration mechanism: S59 phosphorylation controls NREP stability, and migration requires β1 integrin and Rac1 GTPase, with Filamin A as a peripheral binding partner.

    Evidence S59A/S59D mutagenesis, Co-IP/MALDI-TOF MS, dominant-negative β1 integrin, Rac1 siRNA, colocalization

    PMID:16229809

    Open questions at the time
    • Kinase/phosphatase acting on S59 not identified
    • How Filamin A binding couples to Rac1 activation unclear
  7. 2006 Medium

    Showed NREP-induced migration can adopt a RalA-dependent ameboid mode switchable by matrix composition, revealing plasticity in its motility output.

    Evidence RalA siRNA, fibrin vs collagen I matrices, focal adhesion/stress fiber imaging

    PMID:16934802

    Open questions at the time
    • Upstream signal selecting RalA vs Rac1 not defined
    • Single-lab phenotype
  8. 2008 Medium

    Genetic knockouts established organismal roles in learning/memory and the affective component of pain, dissociating these from sensorimotor function.

    Evidence P311-knockout mice, behavioral batteries and formalin pain testing

    PMID:18549486 PMID:18616608

    Open questions at the time
    • Molecular basis of behavioral phenotypes not connected to TGF-β or migration mechanisms
    • Cell types and circuits involved not defined
  9. 2008 Medium

    Identified a non-canonical, retinoic-acid-linked role in lipid-droplet accumulation, distinguishing it from classical adipogenic differentiation.

    Evidence Overexpression/knockdown, lipid quantification, gene profiling, NIH3T3-L1 negative control

    PMID:18664493

    Open questions at the time
    • Direct molecular mediators of lipid synthesis not identified
    • Relationship to later adipogenesis findings unresolved
  10. 2013 High

    Resolved the central mechanism: NREP is an RNA-binding protein that stimulates translation of all three TGF-β isoforms, and this axis controls blood pressure, with KO/transgenic phenotypes rescued by exogenous TGF-β.

    Evidence KO and transgenic mice, blood pressure and contractility assays, polysome fractionation, TGF-β rescue

    PMID:24091331

    Open questions at the time
    • Molecular details of translational activation not yet resolved
    • Did not identify initiation-factor partner
  11. 2014 High

    Provided the molecular mechanism of translational activation: NREP binds TGF-β 5'UTRs and directly engages eIF3b through a defined motif, with disruption abolishing translation.

    Evidence IP/MS, GST pulldown, SPR Kd, EMSA, UV cross-linking, luciferase reporters, polysome fractionation, CD/PONDR

    PMID:25336651

    Open questions at the time
    • Structural basis of the disordered NREP–eIF3b/RNA complex not determined
    • How NREP discriminates TGF-β transcripts from other mRNAs unclear
  12. 2012 Medium

    Added ITGB4BP as a direct interaction partner, expanding the NREP interactome beyond eIF3b and Filamin A.

    Evidence Yeast two-hybrid, Co-IP in HEK293, FRET in tissue

    PMID:22365962

    Open questions at the time
    • Functional consequence of the ITGB4BP interaction not established
    • No epistasis or phenotype linked to this binding
  13. 2019 High

    Generalized the NREP–TGF-β translational axis to organ fibrosis (renal, pulmonary, dermal), establishing it as a pro-fibrotic driver reversible by TGF-β blockade or rescue.

    Evidence KO mice in UUO and bleomycin models, overexpression in human/mouse fibroblasts and EpSCs, TGF-β neutralization and rescue, UTR luciferase, Smad pathway blockade

    PMID:26616407 PMID:27906099 PMID:30230348 PMID:37469904

    Open questions at the time
    • Why a normally short-lived protein achieves sustained pro-fibrotic output in vivo not fully explained
    • Cell-type-specific differences across organs not dissected
  14. 2020 Medium

    Mapped upstream control of NREP itself, identifying TGF-β-induced Meox1 as a transcriptional activator and miR-7a-5p as a 3'UTR repressor, embedding NREP in feedback regulation.

    Evidence ChIP, luciferase reporters, siRNA, in vivo miR-7a-5p agomir with P311-overexpression rescue

    PMID:32411720 PMID:32539181

    Open questions at the time
    • Interplay between transcriptional and miRNA control not integrated
    • Other regulatory inputs likely incomplete
  15. 2022 Medium

    Implicated an mTOR-dependent branch through which NREP modulates macrophage M2 polarization, angiogenesis (VEGF/VEGFR2/ERK), and TGF-βRII expression in wound healing.

    Evidence KO and overexpression models, mTOR/ERK/VEGFR2 inhibition and siRNA, polarization, tube-formation, and wound assays

    PMID:35154140 PMID:35220700 PMID:36309321 PMID:37469904

    Open questions at the time
    • How NREP connects mechanistically to mTOR signaling not defined
    • Whether mTOR effects depend on TGF-β translational axis unclear
  16. 2023 Medium

    Broadened the axis to chondrocyte and hepatic homeostasis and showed NREP is itself an m6A-regulated translational target of YTHDF1, adding an epitranscriptomic control layer.

    Evidence siRNA in chondrocytes and primary hepatocytes, multi-omics, m6A profiling, YTHDF1 knockdown and inhibitor, corneal fibrosis model

    PMID:37354909 PMID:38179126 PMID:42153780

    Open questions at the time
    • Direct molecular basis of hepatic metabolic effects not resolved
    • m6A site mapping on NREP largely predictive
  17. 2024 Medium

    Placed NREP in hypoxic and oncogenic contexts: HIF-1α directly drives NREP transcription to promote breast cancer glycolysis and EMT, and TAD-boundary disruption dysregulates Nrep expression.

    Evidence ChIP, luciferase, loss/gain-of-function, Seahorse, xenograft; engineered TAD deletion/inversion mouse models with RNA-seq

    PMID:38438377 PMID:38697993

    Open questions at the time
    • Whether tumor glycolytic phenotype requires the TGF-β translational axis untested
    • Functional consequence of TAD-driven Nrep dysregulation not characterized

Open questions

Synthesis pass · forward-looking unresolved questions
  • How a disordered, rapidly degraded protein achieves selective, high-fidelity translational activation of TGF-β transcripts, and how its diverse outputs (migration, mTOR, metabolism, neuronal function) are mechanistically partitioned, remains unresolved.
  • No structure of NREP bound to RNA or eIF3b
  • Mechanistic link between mTOR/metabolic roles and the TGF-β translational axis undefined
  • Molecular basis of neuronal and affective-pain phenotypes uncharacterized

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0045182 translation regulator activity 3 GO:0003723 RNA binding 2 GO:0098772 molecular function regulator activity 2
Localization
GO:0005829 cytosol 2 GO:0005886 plasma membrane 2 GO:0005634 nucleus 1
Pathway
R-HSA-162582 Signal Transduction 3 R-HSA-392499 Metabolism of proteins 2 R-HSA-8953854 Metabolism of RNA 2
Partners
EIF3BFLNAITGB1ITGB4BPYTHDF1

Evidence

Reading pass · 29 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2000 P311 encodes an 8-kDa polypeptide that is rapidly degraded by the lactacystin-sensitive ubiquitin/proteasome system and an unidentified metalloprotease, resulting in a protein half-life of approximately 5 minutes. P311 mRNA expression is decreased by co-expression of oncogenic Met receptor tyrosine kinase and its ligand HGF/scatter factor. Proteasome inhibitor (lactacystin) treatment, protein half-life measurement, mRNA expression analysis in transformed cells The Journal of biological chemistry Medium 10660586
2001 P311 supports migration of malignant glioma cells; antisense oligodeoxynucleotide knockdown of P311 reduces glioblastoma cell migration, and the protein localizes at focal adhesions in invasive cells. Antisense oligodeoxynucleotides, integrin activation assays, immunochemistry, laser capture microdissection followed by quantitative RT-PCR Cancer research Medium 11358844
2002 P311 transfection into fibroblast cell lines induces a TGF-β1-independent myofibroblast phenotype characterized by upregulation of SM alpha-actin, SM22, FGF-2, VEGF, PDGF, PDGF receptors, and integrins α3/α5, while simultaneously inhibiting TGF-β1, TGF-β receptor 2, MMP-2, MMP-9, and collagen 1/3 expression. Plasmid transfection into NIH 3T3 and C3H10 T1/2 fibroblasts, Western blot, RT-PCR, exogenous TGF-β1 rescue experiments The Journal of clinical investigation High 12417574
2004 P311 binds to the TGF-β latency-associated protein (LAP) of TGF-β1 and TGF-β2 (but not TGF-β3) as shown by yeast two-hybrid and co-immunoprecipitation. P311 downregulates TGF-β1 and TGF-β2 expression but not TGF-β3. Deletion of P311's PEST domain reverses its effect on TGF-β isoforms. P311 decreases Smad3 activity, consistent with reduced TGF-β autoinduction. Yeast two-hybrid, co-immunoprecipitation, Western blot, deletion mutagenesis of PEST domain, Smad3 activity reporter Biochemical and biophysical research communications High 14985127
2004 Ectopically expressed P311 localizes in the cytoplasm and nucleus of neurons; overexpression of P311 induces p21(WAF1/Cip1) expression leading to PC12 cell differentiation with neuron-like morphology; adenoviral P311 gene transfer promotes neurite outgrowth of dorsal root ganglion and hippocampal neurons in vitro, an effect abolished by Rho kinase activation. Adenovirus-mediated gene transfer, immunofluorescence localization, PC12 differentiation assay, Rho kinase inhibitor, in vivo facial nerve axotomy model Journal of neurochemistry Medium 15485502
2005 P311 is constitutively serine-phosphorylated; dephosphorylation at S59 (near the PEST domain) stabilizes P311 protein and induces glioma cell motility (S59A mutation), while a phosphomimetic S59D mutation causes rapid P311 degradation and reduces migration. P311 binds Filamin A (identified by Co-IP/MALDI-TOF MS) and both colocalize at the cell periphery. P311-induced migration is abolished by β1 integrin dominant-negative inhibitor and requires Rac1 GTPase activity. Site-directed mutagenesis (S59A, S59D), co-immunoprecipitation, MALDI-TOF mass spectrometry, immunofluorescence colocalization, dominant-negative β1 integrin, siRNA knockdown of Rac1 Neoplasia (New York, N.Y.) High 16229809
2006 P311-induced myofibroblasts migrate in an ameboid pattern (lacking focal adhesions, stress fibers, integrins/MMPs clustering) through activation of GTPase RalA; RalA RNAi reverts migration to mesenchymal type. Ameboid migration is supported by fibrin matrix but is switched to mesenchymal migration by collagen I or TGF-β1. RalA siRNA, cell migration assays, matrix composition experiments (fibrin vs collagen I), immunofluorescence for focal adhesions/stress fibers Experimental cell research Medium 16934802
2008 P311 functions in an alternative pathway of lipid-droplet accumulation induced by retinoic acid; P311 upregulates genes associated with lipid synthesis and increases intracellular cholesterol, triglyceride, and lipid droplets. P311 is not required for lipogenesis in the canonical NIH3T3-L1 adipogenic differentiation model. P311 overexpression/knockdown, lipid staining, cholesterol and triglyceride quantification, gene expression profiling, NIH3T3-L1 differentiation assay Journal of cell science Medium 18664493
2008 P311-knockout mice show impaired contextual and cued fear conditioning, social transmission of food preference, Morris water maze performance, and altered emotional responses (reduced fear-potentiated startle), establishing P311 as required for normal learning/memory and emotional responses without affecting motor coordination, balance, hearing, or olfactory discrimination. Gene-targeted P311-knockout mice, behavioral battery (Morris water maze, fear conditioning, fear-potentiated startle, social transmission of food preference) Genes, brain, and behavior Medium 18616608
2008 P311-knockout mice show normal heat and mechanical pain sensitivity and normal inflammatory pain responses, but exhibit significantly attenuated formalin-induced pain avoidance behavior (affective pain component), placing P311 specifically in the affective but not sensory pain pathway. P311-knockout mice, formalin pain test (sensory vs. affective components), heat and mechanical sensitivity tests Molecular pain Medium 18549486
2013 P311 is an RNA-binding protein that stimulates translation of TGF-β1, TGF-β2, and TGF-β3 under steady-state conditions. P311-null mice are markedly hypotensive with defects in vascular smooth muscle contractility due to decreased TGF-β1/β2/β3 protein (but not mRNA) levels; this is fully rescued by exogenous TGF-β1–β3. P311-transgenic mice have elevated TGF-β levels and hypertension, establishing a P311–TGF-β translational axis for blood pressure regulation. P311-knockout and P311-transgenic mice, blood pressure measurement, vascular contractility assays, polysome fractionation, rescue with exogenous TGF-β1–β3, Western blot The Journal of clinical investigation High 24091331
2014 P311 is an intrinsically disordered protein that directly binds eIF3 subunit b (eIF3b) with Kd of 1.26 µM via a central 11-amino acid eIF3b binding motif. P311 also directly binds TGF-β1, -β2, and -β3 5'UTR mRNAs via an RNA recognition motif-like motif. Disruption of P311–eIF3b interaction inhibits TGF-β1/2/3 translation as demonstrated by luciferase reporter assays, polysome fractionation, and Western blot. Immunoprecipitation/mass spectrometry, GST pulldown, surface plasmon resonance (Kd measurement), immunohistochemical colocalization, luciferase reporter assays, polysome fractionation, RNA-protein EMSA, UV cross-linking RNA precipitation, CD spectroscopy (PONDR disorder analysis) The Journal of biological chemistry High 25336651
2012 Integrin β4 binding protein (ITGB4BP) is a direct interaction partner of P311, confirmed by yeast two-hybrid screening, co-immunoprecipitation in HEK293 cells, and fluorescence resonance energy transfer (FRET) in tissue sections. Yeast two-hybrid, co-immunoprecipitation, FRET in tissue sections, immunohistochemistry Life sciences Medium 22365962
2015 P311 promotes renal fibrosis in vivo; P311 knockout mice subjected to unilateral ureteral obstruction show significantly reduced interstitial collagen deposition, α-SMA, TGF-β1, and macrophage infiltration. The pro-fibrotic effect operates via TGF-β1/Smad signaling. P311-knockout mice, unilateral ureteral obstruction model, histology, immunohistochemistry, Western blot Scientific reports Medium 26616407
2016 P311 induces epidermal stem cell (EpSC) to myofibroblast-like cell transdifferentiation via TGF-β1/Smad2/3 signaling. P311 increases TGF-β1 protein without increasing TGF-β1 mRNA (consistent with translational regulation), upregulates TGF-β receptors I/II, and activates Smad2/3. P311 promotes TGF-β1 5'/3'UTR activity. TGF-βRI/II inhibitor LY2109761 and Smad3 siRNA reverse P311-induced transdifferentiation. Adenoviral P311 overexpression in human/mouse EpSCs, Western blot, immunofluorescence, real-time PCR, bisulfite sequencing, luciferase reporter assays, pharmacological (LY2109761) and siRNA (Smad3) pathway blockade, P311-KO mouse wound model Stem cell research & therapy High 27906099
2017 P311 accelerates epidermal stem cell (EpSC) migration and skin wound reepithelialization through activation of RhoA and Rac1 GTPases (but not Cdc42). Specific RhoA and Rac1 inhibitors (but not Cdc42 inhibitor) suppress P311-induced EpSC migration. P311-knockout mouse wounds show impaired reepithelialization. Adenoviral P311 overexpression in human EpSCs, P311-KO mouse wound model, Rho GTPase activity assays, pharmacological inhibitors of RhoA, Rac1, and Cdc42, cell migration assays Stem cells and development Medium 27927130
2019 P311 stimulates TGF-β1, -β2, and -β3 translation in lung fibroblasts. P311-knockout mice subjected to bleomycin-induced pulmonary fibrosis show significantly reduced fibrotic changes and decreased TGF-β1/2/3 levels. Forced P311 expression increases TGF-β levels and collagen production in human and mouse lung fibroblasts. TGF-β-neutralizing antibodies abrogate P311-induced collagen production. Rescue of P311-KO mice with recombinant TGF-β1/2/3 restores fibrosis to wild-type levels. P311-knockout mice with bleomycin lung fibrosis model, adenoviral P311 overexpression in lung fibroblasts, Western blot, TGF-β neutralizing antibodies, cytokine rescue experiments American journal of respiratory cell and molecular biology High 30230348
2019 P311 binds to the PPARγ2 promoter and its knockdown inhibits adipogenic differentiation of 3T3-L1 cells; P311 expression is induced at the onset of adipogenesis and correlates with PPARγ2 and C/EBPα induction. siRNA knockdown, 3T3-L1 adipogenesis model, chromatin immunoprecipitation (ChIP) for PPARγ2 promoter binding, Western blot Biochemical and biophysical research communications Medium 31146912
2020 Meox1 (mesenchyme homeobox 1), induced by TGF-β1, binds the P311 core promoter and increases P311 transcriptional activity. This Meox1-mediated P311 transcription contributes to altered migration and proliferation of human dermal fibroblasts. Bioinformatics promoter analysis, luciferase reporter assays, chromatin immunoprecipitation (ChIP), siRNA knockdown of Meox1, cell migration and proliferation assays Frontiers in molecular biosciences Medium 32411720
2020 miR-7a-5p directly targets the 3'UTR of P311 mRNA and suppresses P311 expression; butyrate alleviates diabetic kidney fibrosis in part by inducing miR-7a-5p, which suppresses P311, thereby reducing TGF-β1 translation. Overexpression of P311 offsets butyrate's inhibition of TGF-β1. 3'UTR luciferase reporter assay, miRNA sequencing, miR-7a-5p agomir in db/db mice, Western blot, RT-PCR, P311 overexpression rescue FASEB journal Medium 32539181
2022 P311 promotes M2 polarization of macrophages by upregulating IL-4 receptor expression and activating the IL-4 receptor–STAT6 signaling pathway. P311 regulation of IL-4 receptor expression involves the mTOR signaling pathway. P311-knockout mice, macrophage polarization assays, Western blot, flow cytometry for IL-4R/STAT6, mTOR inhibitor experiments, wound healing model The Journal of investigative dermatology Medium 36309321
2022 P311 promotes angiogenesis in mesenchymal stem cells by increasing VEGF production through the mTOR signaling pathway. P311 overexpression in MSCs, VEGF ELISA, tube formation assay, mTOR inhibitor, in vivo wound model Frontiers in immunology Medium 35154140
2022 P311 enhances angiogenesis in human microvascular endothelial cells by activating the VEGFR2/ERK1/2 signaling pathway; siRNA knockdown of VEGFR2 or ERK1/2 inhibitor treatment abolishes P311-induced tube formation. Adenoviral P311 overexpression in HMEC-1 cells, Western blot for p-VEGFR2 and p-ERK1/2, siRNA-VEGFR2 knockdown, ERK1/2 inhibitor, tube formation assay, scratch migration assay Zhonghua shao shang yu chuang mian xiu fu za zhi Medium 35220700
2022 P311 promotes fibroblast differentiation and granulation tissue formation by upregulating TGF-βRII (type II TGF-β receptor) expression and activating the TGF-βRII–Smad signaling pathway via the mTOR pathway. P311-knockout and wild-type mice with full-thickness excisional wounds, Western blot for TGF-βRII and Smad proteins, mTOR inhibitor, in vitro fibroblast differentiation assays Burns & trauma Medium 37469904
2023 NREP knockdown in primary human hepatocytes alters one-carbon metabolism, increases cholesterol esters and triglycerides, decreases phosphatidylcholine levels, and activates calcium signaling pathways, implicating NREP in hepatic lipid/metabolic homeostasis. siRNA knockdown in primary human hepatocytes, RNA-sequencing, lipidomics, antibody microarray (signalomics) Cell chemical biology Medium 37354909
2023 NREP knockdown in chondrocytes inactivates the TGF-β1/Smad2/3 signaling pathway, resulting in downregulation of anabolic markers Col2a1 and Sox9 and upregulation of catabolic markers MMP3 and MMP13, and reduced chondrocyte proliferation. siRNA knockdown of NREP in chondrocytes, Western blot for p-Smad2/3, RT-qPCR, CCK-8 and EdU proliferation assays, OA mouse model with IHC Journal of orthopaedic translation Medium 38179126
2023 YTHDF1 binds m6A-modified NREP mRNA and promotes its translation; YTHDF1 depletion reduces NREP protein levels and impairs TGF-β–Smad signaling, keratocyte proliferation, migration, and fibroblast-to-myofibroblast differentiation in corneal fibrosis. siRNA knockdown of NREP and YTHDF1, SRAMP m6A site prediction, LC-MS m6A profiling, CCK-8, scratch assay, immunofluorescence, Western blot, in vivo alkali burn corneal fibrosis model, YTHDF1 inhibitor (SKLB-Y13) Investigative ophthalmology & visual science Medium 42153780
2024 HIF-1α directly binds to the NREP promoter to increase NREP transcriptional activity under hypoxia. NREP promotes breast cancer cell glycolysis (increased glucose consumption, ATP, lactate, glucose transporter expression), cell proliferation, migration, invasion, and EMT. Luciferase reporter system, chromatin immunoprecipitation (ChIP), siRNA/overexpression of NREP, HIF-1α inhibition, Seahorse glycolysis assay, cell cycle analysis, apoptosis assay, in vivo xenograft Cell death discovery Medium 38697993
2024 Structural variations disrupting the TAD boundary in the Epb41l4a/EPB41L4A locus cause dysregulation of Nrep gene expression, as demonstrated in mouse models with deletion and inversion mutations analyzed by RNA-seq. CRISPR/engineered mouse models (deletion and inversion), RNA-seq, 3D genome/TAD analysis Scientific reports Medium 38438377

Source papers

Stage 0 corpus · 62 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2023 H3K18 lactylation promotes the progression of arsenite-related idiopathic pulmonary fibrosis via YTHDF1/m6A/NREP. Journal of hazardous materials 132 37742376
2001 Identification and validation of P311 as a glioblastoma invasion gene using laser capture microdissection. Cancer research 111 11358844
2002 P311 induces a TGF-beta1-independent, nonfibrogenic myofibroblast phenotype. The Journal of clinical investigation 69 12417574
2010 Investigating the role of P311 in the hypertrophic scar. PloS one 55 20404911
2005 Regulation of glioma cell migration by serine-phosphorylated P311. Neoplasia (New York, N.Y.) 49 16229809
2004 P311 accelerates nerve regeneration of the axotomized facial nerve. Journal of neurochemistry 49 15485502
2022 Promoting Re-epithelialization in an oxidative diabetic wound microenvironment using self-assembly of a ROS-responsive polymer and P311 peptide micelles. Acta biomaterialia 48 36113723
2015 P311 promotes renal fibrosis via TGFβ1/Smad signaling. Scientific reports 43 26616407
2020 Butyrate alleviates diabetic kidney disease by mediating the miR-7a-5p/P311/TGF-β1 pathway. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 41 32539181
2013 Blood pressure homeostasis is maintained by a P311-TGF-β axis. The Journal of clinical investigation 34 24091331
2000 Regulation of P311 expression by Met-hepatocyte growth factor/scatter factor and the ubiquitin/proteasome system. The Journal of biological chemistry 34 10660586
2008 Behavioral characterization of P311 knockout mice. Genes, brain, and behavior 33 18616608
2014 Novel RNA-binding protein P311 binds eukaryotic translation initiation factor 3 subunit b (eIF3b) to promote translation of transforming growth factor β1-3 (TGF-β1-3). The Journal of biological chemistry 31 25336651
2006 Identification of P311 as a potential gene regulating alveolar generation. American journal of respiratory cell and molecular biology 31 16484684
2006 Altered expression of FHL1, CARP, TSC-22 and P311 provide insights into complex transcriptional regulation in pacing-induced atrial fibrillation. Biochimica et biophysica acta 31 17174532
2004 P311 binds to the latency associated protein and downregulates the expression of TGF-beta1 and TGF-beta2. Biochemical and biophysical research communications 31 14985127
2019 P311 Promotes Lung Fibrosis via Stimulation of Transforming Growth Factor-β1, -β2, and -β3 Translation. American journal of respiratory cell and molecular biology 30 30230348
2020 Effects of IL-1β and TNF-α on the Expression of P311 in Vascular Endothelial Cells and Wound Healing in Mice. Frontiers in physiology 27 33329015
2016 P311 induces the transdifferentiation of epidermal stem cells to myofibroblast-like cells by stimulating transforming growth factor β1 expression. Stem cell research & therapy 25 27906099
1995 Cloning and characterization of pentylenetetrazol-related cDNA, PTZ-17. Brain research 24 7537161
2017 P311 Accelerates Skin Wound Reepithelialization by Promoting Epidermal Stem Cell Migration Through RhoA and Rac1 Activation. Stem cells and development 23 27927130
2006 P311-induced myofibroblasts exhibit ameboid-like migration through RalA activation. Experimental cell research 23 16934802
2022 P311 Promotes IL-4 Receptor‒Mediated M2 Polarization of Macrophages to Enhance Angiogenesis for Efficient Skin Wound Healing. The Journal of investigative dermatology 22 36309321
2022 P311 Facilitates the Angiogenesis and Wound Healing Function of MSCs by Increasing VEGF Production. Frontiers in immunology 20 35154140
2006 Porcine congenital splayleg is characterised by muscle fibre atrophy associated with relative rise in MAFbx and fall in P311 expression. BMC veterinary research 20 16869957
2008 Involvement of P311 in the affective, but not in the sensory component of pain. Molecular pain 19 18549486
2017 P311 Deficiency Leads to Attenuated Angiogenesis in Cutaneous Wound Healing. Frontiers in physiology 16 29270129
2015 Adenovirus-mediated P311 inhibits TGF-β1-induced epithelial-mesenchymal transition in NRK-52E cells via TGF-β1-Smad-ILK pathway. Bioscience trends 16 26559022
2018 P311, Friend, or Foe of Tissue Fibrosis? Frontiers in pharmacology 15 30369881
2014 P311 modulates hepatic stellate cells migration. Liver international : official journal of the International Association for the Study of the Liver 14 25243526
2018 Adenovirus-mediated P311 ameliorates renal fibrosis through inhibition of epithelial-mesenchymal transition via TGF-β1-Smad-ILK pathway in unilateral ureteral obstruction rats. International journal of molecular medicine 12 29436600
2022 P311 promotes type II transforming growth factor-β receptor mediated fibroblast activation and granulation tissue formation in wound healing. Burns & trauma 11 37469904
2021 Overexpression of NREP Promotes Migration and Invasion in Gastric Cancer Through Facilitating Epithelial-Mesenchymal Transition. Frontiers in cell and developmental biology 11 34746143
2008 P311 functions in an alternative pathway of lipid accumulation that is induced by retinoic acid. Journal of cell science 11 18664493
2012 Identification of ITGB4BP as a new interaction protein of P311. Life sciences 10 22365962
2020 Molecular Mechanism of Mesenchyme Homeobox 1 in Transforming Growth Factor β1-Induced P311 Gene Transcription in Fibrosis. Frontiers in molecular biosciences 9 32411720
2024 Structural variants in the Epb41l4a locus: TAD disruption and Nrep gene misregulation as hypothetical drivers of neurodevelopmental outcomes. Scientific reports 8 38438377
2019 P311, a novel intrinsically disordered protein, regulates adipocyte development. Biochemical and biophysical research communications 8 31146912
2009 Expression of P311, a transforming growth factor beta latency-associated protein-binding protein, in human kidneys with IgA nephropathy. International urology and nephrology 8 19946746
1998 Expression of seizure-related PTZ-17 is induced by potassium deprivation in cerebellar granule cells. Biochemical and biophysical research communications 8 9813137
1997 Molecular mechanism of regulation of pentylenetetrazol-induced calcium entry by 3'-untranslated region of a seizure-related cDNA, PTZ-17, in Xenopus oocytes. Brain research. Molecular brain research 7 9221901
2017 Shenqi detoxification granule combined with P311 inhibits epithelial-mesenchymal transition in renal fibrosis via TGF-β1-Smad-ILK pathway. Bioscience trends 6 29311449
2024 NREP, transcriptionally upregulated by HIF-1α, aggravates breast cancer cell growth and metastasis by promoting glycolysis. Cell death discovery 5 38697993
2024 Seabuckthorn polysaccharide alleviates renal fibrosis in a mouse model of diabetic nephropathy via p311/TGFβ1/Fstl1 signaling pathway. Pathology, research and practice 5 39951942
2022 MicroRNA-124-3p alleviates cerebral ischaemia-induced neuroaxonal damage by enhancing Nrep expression. Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association 5 36535134
2020 P311 regulates distal lung development via its interaction with several binding proteins. Mechanisms of development 5 32682987
2023 NREP contributes to development of NAFLD by regulating one-carbon metabolism in primary human hepatocytes. Cell chemical biology 4 37354909
2015 Role of P311 in interleukin-1α-induced epithelial to myofibroblast transition in kidney tubular epithelial cells. Renal failure 4 26335191
2024 Pirfenidone Downregulates eIF6, P311, and TGF-β Expression and Improves Liver Fibrosis Induced by Bile Duct Ligation in Wistar Rats: Evidence for Liver Regeneration. DNA and cell biology 3 39681345
2023 The silencing of NREP aggravates OA cartilage damage through the TGF-β1/Smad2/3 pathway in chondrocytes. Journal of orthopaedic translation 3 38179126
2019 Reconstruction and Functional Annotation of P311 Protein-Protein Interaction Network Reveals Its New Functions. Frontiers in genetics 3 30838032
2016 [Interaction between P311 and transforming growth factor beta 1 and its effect on the function of murine fibroblasts]. Zhonghua shao shang za zhi = Zhonghua shaoshang zazhi = Chinese journal of burns 3 27093932
2022 [Effect of P311 microspheres-loaded thermosensitive chitosan hydrogel on the wound healing of full-thickness skin defects in rats]. Zhonghua shao shang yu chuang mian xiu fu za zhi 2 36299202
2021 The expression pattern, polymorphisms and association analyses of the porcine NREP gene. Journal of animal breeding and genetics = Zeitschrift fur Tierzuchtung und Zuchtungsbiologie 1 34487372
2017 [Effects of hypoxia inducible factor-1α on P311 and its influence on the migration of murine epidermal stem cells]. Zhonghua shao shang za zhi = Zhonghua shaoshang zazhi = Chinese journal of burns 1 28651420
2010 [Expression and significance of P311 and ITGB4BP in non-small cell lung cancer]. Zhonghua zhong liu za zhi [Chinese journal of oncology] 1 21029697
2026 YTHDF1-Mediated m6A Modification of NREP Promotes Corneal Fibrosis via TGF-β-Smad Signaling. Investigative ophthalmology & visual science 0 42153780
2026 Intracellular Delivery of P311 Protein and Scavenge of ROS by Targeting Liposome Promote Fibroblast Differentiation to Myofibroblast and Diabetic Wound Healing via Regulating the GDF-15 Pathway. ACS applied materials & interfaces 0 42219784
2025 Hypoxic human adipose mesenchymal stem cells-derived extracellular vesicles induce P311 expression and inhibit activation and injury of human brain microvascular endothelial cells. Clinical hemorheology and microcirculation 0 39973441
2022 [Effects of P311 on the angiogenesis ability of human microvascular endothelial cell 1 in vitro and its molecular mechanism]. Zhonghua shao shang yu chuang mian xiu fu za zhi 0 35220700
2022 P311 knockdown alleviates hyperoxia-induced injury by inactivating the Smad3 signaling pathway in type II alveolar epithelial cells. Molecular and cellular biochemistry 0 35779227
2019 Corrigendum: Reconstruction and Functional Annotation of P311 Protein-Protein Interaction Network Reveals Its New Functions. Frontiers in genetics 0 31762773

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