Affinage

PEBP1

Phosphatidylethanolamine-binding protein 1 · UniProt P30086

Length
187 aa
Mass
21.1 kDa
Annotated
2026-06-10
100 papers in source corpus 26 papers cited in narrative 26 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

PEBP1 (RKIP) is a multifunctional small scaffold/regulatory protein that controls cell fate decisions by physically gating signaling kinases and lipid-oxidizing enzymes (PMID:10490027, PMID:29053969). Its founding function is direct inhibition of the Raf/MEK/ERK cascade: it binds Raf-1 and MEK without being a substrate, competitively disrupting the Raf-1/MEK interaction to block MEK phosphorylation and ERK/AP-1 activation, and it similarly antagonizes B-Raf kinase activity (PMID:10490027, PMID:15782137). This inhibitory grip is conditional — PKC phosphorylation releases Raf-1 and converts RKIP into a GRK2 inhibitor, establishing it as a phosphorylation-controlled molecular switch between two kinase-inhibitory states (PMID:15313400). Through ERK suppression, PEBP1 restrains tumor invasion and metastasis, acting via GSK3β stabilization, a let-7/HMGA2/BACH1 axis, RhoA/GEF-H1-dependent E-cadherin localization, and repression of MMP13 (PMID:21303975, PMID:21873975, PMID:34465801, PMID:26308852). A distinct moonlighting activity emerged from its association with 15-lipoxygenases (15LO1/15LO2): the PEBP1/15LOX complex redirects enzyme substrate specificity from free fatty acids to phosphatidylethanolamine, generating the pro-ferroptotic death signal 15-HpETE-PE, a reaction requiring membrane-triggered conformational change and tunable by point mutations (P112E) and complex-selective inhibitors (PMID:29053969, PMID:37678654, PMID:37327313). PEBP1 thereby integrates death-pathway choices, competing with RIP3 to switch cells between necroptosis and ferroptosis and binding LC3 through an LIR motif to modulate autophagy via AKT–mTORC1 (PMID:35101798, PMID:27540684, PMID:32513718). It further suppresses inflammation by sequestering ASC to block NLRP1/3/NLRC4 inflammasome assembly, promotes IL-17R–Act1 signaling, and enforces HIV-1 latency by dephosphorylating Raf1/ERK and IKK/IκB to sequester NF-κB (PMID:32901127, PMID:29674348, PMID:32924251). PEBP1 protein levels are themselves controlled by phosphorylation-triggered chaperone-mediated autophagy (CDK5/T42), CELF1-mediated translational repression, and proteasomal degradation directed by UBE3C and RIPK4 (PMID:25104559, PMID:34669021, PMID:35840930, PMID:29436617).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1999 High

    Established the founding mechanism: how an endogenous protein restrains the Raf/MEK/ERK cascade, by showing RKIP physically competes Raf-1 away from MEK.

    Evidence Yeast two-hybrid, in vitro binding, Co-IP, and antisense/antibody microinjection in cells

    PMID:10490027

    Open questions at the time
    • Did not resolve the structural basis of Raf-1/MEK competition
    • Did not address regulation of RKIP itself
  2. 2004 Medium

    Answered how RKIP inhibitory specificity is toggled, defining a PKC-phosphorylation switch from Raf-1 inhibition to GRK2 inhibition.

    Evidence Biochemical/pharmacological assays summarized in a review citing primary work

    PMID:15313400

    Open questions at the time
    • Abstracted from review, limiting direct method verification
    • Stoichiometry and kinetics of the switch not defined
  3. 2005 High

    Extended Raf inhibition to B-Raf, showing the inhibitory scope is broader than Raf-1 alone.

    Evidence Yeast two-hybrid, Co-IP, and kinase activity assay with ectopic expression

    PMID:15782137

    Open questions at the time
    • Did not establish whether B-Raf and Raf-1 inhibition use identical interfaces
  4. 2006 Medium

    Identified PEBP1 as a calpain substrate and a partial proteasome inhibitor, first hints that its stability and protease interplay are regulated.

    Evidence In vitro proteolysis, in situ brain injury model, proteasome activity assay

    PMID:17018026

    Open questions at the time
    • Physiological relevance of calpain cleavage uncharacterized
    • Mechanism of proteasome inhibition not defined
  5. 2011 Medium

    Connected RKIP loss to metastasis programs, defining downstream GSK3β-stabilizing and let-7/HMGA2/BACH1 axes that drive EMT and bone-metastasis genes.

    Evidence Co-IP, knockdown/overexpression with phosphorylation readouts, and tumor expression analysis with reporter validation

    PMID:21303975 PMID:21873975

    Open questions at the time
    • Single-lab pathway models
    • Direct versus indirect regulation of miRNA axis not fully separated
  6. 2012 Medium

    Mapped the conserved ligand-binding pocket and additional partners (MDA-9/syntenin), clarifying that pocket occupancy and adjacent residues govern Raf-1 binding.

    Evidence NMR chemical shift mapping and native MS; Co-IP and phosphorylation/in vivo dissemination assays for MDA-9

    PMID:22558375 PMID:23066033

    Open questions at the time
    • Functional consequence of GTP/FMN binding unresolved
    • No crystal structure of Raf-1-bound complex
  7. 2014 High

    Revealed how PEBP1 levels are controlled, defining CDK5 phosphorylation at T42 that releases Raf-1 and triggers Hsc70-dependent chaperone-mediated autophagy degradation in neurodegeneration.

    Evidence In vitro CDK5 kinase assay, T42 mutagenesis, CMA degradation assay, PD mouse and patient samples

    PMID:25104559

    Open questions at the time
    • Single lab
    • Generality of CMA route beyond neurons not established
  8. 2016 High

    Defined a non-kinase function, showing a functional LIR motif binds LC3 and negatively regulates autophagy via AKT–mTORC1/ULK1, gated by Ser153 phosphorylation.

    Evidence Co-IP, LIR mutagenesis (AXXA), autophagy flux, and pathway phosphorylation analysis

    PMID:27540684

    Open questions at the time
    • Single lab
    • How LC3 binding mechanistically alters AKT–mTORC1 not fully resolved
  9. 2017 High

    Established the ferroptosis mechanism, showing the PEBP1/15LOX complex reprograms enzyme specificity toward phosphatidylethanolamine to generate the proximate HpETE-PE death signal.

    Evidence Co-IP, redox lipidomics, and genetic loss-of-function across airway, renal, and neuronal ferroptosis models

    PMID:29053969

    Open questions at the time
    • Structural basis of substrate redirection not yet resolved at this stage
  10. 2018 High

    Expanded PEBP1 into immune signaling and degradation control, showing it builds the IL-17RA–Act1 complex and is degraded by RIPK4 to license RAF1/MEK/ERK-driven cancer invasion.

    Evidence Co-IP of ternary complex with RKIP-KO EAE/adoptive transfer; high-throughput screen with PEBP1 rescue and invasion assays

    PMID:29436617 PMID:29674348

    Open questions at the time
    • Mechanism of RIPK4-directed degradation (E3 ligase) not identified in this study
    • Direct versus scaffolded IL-17R assembly not structurally resolved
  11. 2020 High

    Positioned PEBP1 as an integrator of death and inflammation, linking ferroptosis to compensatory autophagy, blocking inflammasome assembly via ASC, and enforcing HIV-1 latency by sequestering NF-κB.

    Evidence Co-IP/lipidomics/autophagy flux (15LO1–PEBP1–LC3); ASC competition with inflammasome readouts in macrophages and KO mice; genome-wide CRISPR screen plus NF-κB localization in latency models; complex-specific Fer-1 inhibition with computational docking

    PMID:32513718 PMID:32901127 PMID:32924251 PMID:33126055

    Open questions at the time
    • How a single protein partitions among 15LOX, LC3, ASC, and NF-κB pathways in one cell is unresolved
    • Inhibitor binding sites inferred computationally
  12. 2022 High

    Defined the death-mode switch and a degradation route, showing PEBP1 binds RIP3 to restrain necroptosis with 15LOX competing it toward ferroptosis, and that circPOLR2A/UBE3C ubiquitinates PEBP1.

    Evidence Co-IP, Rip3K51A mouse rescue, redox lipidomics, competition assays; RNA pull-down/MS/RIP and ubiquitination assays for UBE3C

    PMID:35101798 PMID:35840930

    Open questions at the time
    • Affinity-based competition thresholds in vivo not quantified
    • circPOLR2A/UBE3C axis is single-lab
  13. 2023 High

    Resolved the catalytic mechanism of the ferroptotic complex, showing membrane association triggers a conformational change enabling PE substrate access, and developed complex-selective inhibitors.

    Evidence Molecular dynamics, P112E mutagenesis with LC-MS/MS lipidomics; FerroLOXIN inhibitor studies with docking and in vivo testing

    PMID:37327313 PMID:37678654

    Open questions at the time
    • No experimental high-resolution structure of the membrane-bound complex
    • In vivo therapeutic window of inhibitors not defined

Open questions

Synthesis pass · forward-looking unresolved questions
  • How PEBP1 dynamically partitions its single ligand pocket and interaction surfaces among competing partners (Raf/MEK, GRK2, 15LOX, LC3, ASC, RIP3) within one cell, and what governs that allocation, remains unresolved.
  • No quantitative competition model across partners
  • No structure of PEBP1 in its alternative complexes
  • Cell-type determinants of which function dominates unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 4 GO:0098772 molecular function regulator activity 4 GO:0008289 lipid binding 3 GO:0140096 catalytic activity, acting on a protein 2
Localization
GO:0005829 cytosol 2 GO:0005886 plasma membrane 2
Pathway
R-HSA-162582 Signal Transduction 3 R-HSA-1643685 Disease 3 R-HSA-9612973 Autophagy 3 R-HSA-168256 Immune System 2 R-HSA-5357801 Programmed Cell Death 2
Partners
ALOX15BRAFGRK2MAP1LC3BMAP2K1PYCARDRAF1RIPK3
Complex memberships
IL-17RA–Act1 complexPEBP1/15-lipoxygenase complexcircPOLR2A–UBE3C–PEBP1 complex

Evidence

Reading pass · 26 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 RKIP (PEBP1) binds to Raf-1 and MEK in vitro and co-immunoprecipitates with Raf-1 and MEK from cell lysates, competitively disrupting the Raf-1/MEK interaction and thereby inhibiting MEK phosphorylation and ERK activation. RKIP is not a substrate for Raf-1 or MEK. Overexpression inhibits MEK/ERK/AP-1 activation; antisense or antibody microinjection activates MEK/ERK/AP-1. Yeast two-hybrid screen, in vitro binding assay, co-immunoprecipitation, confocal colocalization, reporter gene assay, antisense RNA/antibody microinjection Nature High 10490027
2004 PKC phosphorylates RKIP, causing release of Raf-1 and activation of MEK/ERK. The phosphorylated form of RKIP then binds to and inhibits G-protein-coupled receptor kinase 2 (GRK2), resulting in sustained G-protein signaling — establishing RKIP as a molecular switch between two distinct kinase-inhibitory states. Biochemical/pharmacological assays described in review citing primary experimental work Biochemical pharmacology Medium 15313400
2005 RKIP interacts with B-Raf (in addition to Raf-1) and antagonizes its kinase activity. Yeast two-hybrid and co-immunoprecipitation confirmed RKIP–B-Raf interaction; ectopic RKIP expression reduced B-Raf kinase activity independently of its known inhibitory action on Raf-1. Yeast two-hybrid, co-immunoprecipitation, kinase activity assay, ectopic overexpression Oncogene High 15782137
2017 PEBP1 forms a complex with 15-lipoxygenase isoforms 15LO1 and 15LO2, altering their substrate specificity from free polyunsaturated fatty acids to phosphatidylethanolamine (PE), enabling generation of hydroperoxy-PE (HpETE-PE) — the proximate ferroptotic death signal. This PEBP1/15LO complex is required for ferroptotic cell death in airway epithelial cells, kidney epithelial cells, and neurons. Co-immunoprecipitation, lipidomic analysis (redox lipidomics), cell-based ferroptosis models (airway, renal, neuronal), genetic loss-of-function Cell High 29053969
2011 RKIP binds GSK3 proteins and maintains GSK3β protein levels and active form. RKIP depletion activates p38 MAPK which phosphorylates GSK3β at inhibitory T390, de-repressing GSK3β substrates cyclin D, β-catenin, SNAIL and SLUG, promoting cell-cycle progression and EMT. Co-immunoprecipitation, RKIP knockdown/overexpression, phosphorylation assays, Western blot Cancer research Medium 21303975
2011 RKIP inhibits breast tumor metastasis in part through a pathway involving let-7 miRNA, which suppresses let-7 targets HMGA2 and BACH1; BACH1 is a transcription factor that induces MMP1 expression and promotes bone metastasis genes (MMP1, OPN, CXCR4). Statistical analysis of tumor gene expression combined with experimental validation (overexpression, knockdown, reporter assays) The EMBO journal Medium 21873975
2014 CDK5 phosphorylates RKIP at T42 in neurons, causing release of Raf-1. T42 phosphorylation also exposes the C-terminal motif 'KLYEQ', recognized by chaperone Hsc70, leading to chaperone-mediated autophagy (CMA) degradation of RKIP. This CDK5/RKIP/ERK pathway is activated in Parkinson's disease models, leading to ERK overactivation, S-phase re-entry, and neuronal loss. In vitro kinase assay (CDK5 phosphorylation), mutagenesis (T42), co-immunoprecipitation (Hsc70/RKIP), CMA degradation assay, PD mouse models and patient brain samples Neurobiology of aging High 25104559
2016 PEBP1 contains a functional LC3-interacting region (LIR) motif (WXXL) that mediates direct binding to PE-unconjugated LC3. PEBP1 overexpression inhibits starvation-induced autophagy by activating AKT–mTORC1 signaling and suppressing ULK1 activity. Mutation of the LIR motif (AXXA) disrupts LC3 binding but promotes rather than inhibits autophagy. Phosphorylation of PEBP1 at Ser153 dissociates the PEBP1–LC3 complex to allow autophagy induction. Co-immunoprecipitation, LIR motif mutagenesis, autophagy flux assays, AKT/mTORC1/ULK1 phosphorylation analysis, overexpression/knockdown Autophagy High 27540684
2020 PEBP1 interacts with both 15LO1 (proferroptotic) and the autophagic protein LC3, acting as a rheostat. The 15LO1-PEBP1-generated ferroptotic lipid 15-HpETE-PE promotes LC3-I lipidation to stimulate compensatory autophagy, protecting cells from ferroptotic death. Co-immunoprecipitation, lipidomic analysis, autophagy flux assays, human airway epithelial cell models, asthma patient samples Proceedings of the National Academy of Sciences of the United States of America High 32513718
2020 Ferrostatin-1 (Fer-1) does not inhibit 15LOX alone, but effectively inhibits HpETE-PE production by the 15LOX/PEBP1 complex. Computational molecular modeling shows Fer-1 binds to the 15LOX/PEBP1 complex at three sites, disrupting allosteric motions required for catalysis. Biochemical inhibition assay (15LOX alone vs. complex), computational molecular docking/modeling, redox lipidomics in nine ferroptosis cell/tissue models Redox biology High 33126055
2020 PEBP1 suppresses HIV-1 transcription and induces latency by de-phosphorylating Raf1/ERK/IκB and IKK/IκB signaling pathways, sequestering NF-κB in the cytoplasm and preventing transcriptional activation of HIV-1. Identified via genome-wide CRISPR-Cas9 knockout screen. Genome-wide CRISPR-Cas9 knockout screen, phosphorylation assays, NF-κB nuclear translocation assays, HIV latency models (multiple cell lines + primary CD4+ T cells from ART patients) EMBO reports High 32924251
2020 RKIP directly binds ASC (apoptosis-associated speck-like protein containing a CARD domain) and competes with NLRP1, NLRP3, and NLRC4 for ASC interaction, thereby interrupting inflammasome assembly and activation and suppressing caspase-1 activation and IL-1β secretion. Co-immunoprecipitation, overexpression/knockdown in THP-1 cells and primary macrophages, RKIP-deficient mouse models (Alum-induced peritonitis, Salmonella infection) Cellular & molecular immunology High 32901127
2018 RKIP directly interacts with IL-17RA and Act1 to promote formation of an IL-17R–Act1 complex, resulting in enhanced MAPK and NF-κB activation and downstream pro-inflammatory cytokine production. RKIP-deficient mice show ameliorated experimental autoimmune encephalomyelitis (EAE) specifically through the Th17-mediated pathway. Co-immunoprecipitation (RKIP with IL-17RA and Act1), RKIP-knockout mouse EAE model, adoptive T-cell transfer, cytokine production assays EMBO reports High 29674348
2022 PEBP1 complexes with RIP3 kinase and inhibits necroptosis. When 15LOX is expressed at elevated levels (higher affinity for PEBP1), it competes with RIP3 to sequester PEBP1, switching cell death from necroptosis to ferroptosis. RIP3 K51A kinase-inactive mice show increased ferroptotic burden rescued by anti-ferroptotic compounds. Co-immunoprecipitation (PEBP1–RIP3), genetic models (Rip3K51A/K51A mice), redox lipidomics, biochemical competition assays, computational structural analysis Redox biology High 35101798
2022 CircPOLR2A interacts with both UBE3C and PEBP1 to form a ternary RNA-protein complex. UBE3C acts as a specific E3 ubiquitin ligase for PEBP1, and circPOLR2A enhances UBE3C-mediated ubiquitination and proteasomal degradation of PEBP1, thereby activating ERK signaling in clear cell renal cell carcinoma. RNA pull-down, mass spectrometry, RIP assay, Co-IP, Western blot (ubiquitination), rescue experiments Molecular cancer Medium 35840930
2018 RIPK4 promotes proteasome-mediated degradation of PEBP1, thereby activating RAF1/MEK/ERK signaling. Suppression of PEBP1 degradation eliminates RIPK4-induced ERK activation and pancreatic cancer cell migration/invasion. High-throughput screening, Western blot (proteasome-mediated PEBP1 degradation), PEBP1 rescue experiments, migration/invasion assays International journal of oncology Medium 29436617
2009 Human and bovine PEBP1 directly interact with morphine glucuronides (M3G and M6G) but not with morphine itself. M6G binds PEBP1 in a manner similar to the reference ligand phosphatidylethanolamine (PE), and PEBP1 displays similar affinity for PE, M6G, and M3G. Noncovalent electrospray ionization mass spectrometry (ESI-MS) of protein–ligand complexes Medical science monitor Medium 19564817
2010 NMR screening identified that the conserved ligand-binding pocket of RKIP binds phospholipid DHPE and three novel small-molecule ligands. Occupation of this pocket by DHPE regulates RKIP interaction with Raf-1; phosphorylation of RKIP at Ser-153 also regulates Raf-1 binding. The newly identified ligands did not affect RKIP–Raf-1 binding or RKIP phosphorylation. High-resolution heteronuclear NMR spectroscopy (chemical shift perturbation), compound library screening PloS one Medium 20463977
2012 NMR mapping of human PEBP1 binding sites for GTP, FMN, and Raf-1 peptides (phosphorylated and non-phosphorylated) shows all ligands bind to the same region centered on the conserved ligand-binding pocket. Residues in the vicinity of, rather than within, the pocket appear required for Raf-1 interaction. NMR (chemical shift perturbation mapping), native mass spectrometry (KD measurement) PloS one Medium 22558375
2006 PEBP1 is a substrate of calpain protease in vitro and in situ (brain injury model). PEBP1 also inhibits the chymotrypsin-like activity of the 26S proteasome by approximately 30% in vitro. In vitro proteolysis assay, in situ brain injury model, proteasome activity assay Journal of neurochemistry Medium 17018026
2023 Computational simulations and lipidomic experiments show that membrane association of the 15LOX-1/PEBP1 complex triggers a conformational change facilitating access of stearoyl/arachidonoyl-PE (SAPE) substrate to the catalytic site. PEBP1 P112E mutation significantly impairs generation of the predominant ferroptotic product 15-HpETE-PE. The complex produces 15-HpETE-PE and 12-HpETE-PE at a 5:1 ratio. Computational molecular dynamics simulation, mutagenesis (P112E), LC-MS/MS lipidomics, membrane interaction assays Free radical biology & medicine High 37678654
2023 FerroLOXIN-1 and -2 inhibit ferroptosis by specifically interacting with the 15LOX-2/PEBP1 complex: one compound alters substrate (ETE-PE) binding pose nonproductively, the other blocks the predominant oxygen channel, preventing ETE-PE peroxidation. Effects are not due to radical scavenging or iron chelation. Biochemical assay (15LOX/PEBP1 complex vs. 15LOX alone), computational docking, redox lipidomics, cell biology models, in vivo testing Proceedings of the National Academy of Sciences of the United States of America High 37327313
2012 MDA-9/syntenin transcriptionally downregulates RKIP, and MDA-9 physically interacts with RKIP in melanoma cells. This interaction correlates with suppression of FAK and c-Src phosphorylation, blocking MDA-9-mediated FAK/c-Src complex formation needed for metastatic signaling. Tumor array, co-immunoprecipitation (MDA-9–RKIP), phosphorylation assays (FAK/c-Src), ectopic RKIP expression, in vivo tumor dissemination assay Cancer research Medium 23066033
2021 RKIP activates RhoA in an Erk2- and GEF-H1-dependent manner to enhance E-cadherin membrane localization and inhibit CCL5 expression, thereby suppressing breast cancer cell invasion and metastasis. RhoA activity assay, co-immunoprecipitation, loss/gain-of-function (RKIP, GEF-H1), E-cadherin localization (imaging), CCL5 expression analysis Scientific reports Medium 34465801
2021 CELF1 (RNA-binding protein) directly binds to fragment 1 within the 3'UTR of PEBP1 mRNA (shown by RNA immunoprecipitation and biotin pull-down), post-transcriptionally suppressing PEBP1 protein expression without affecting PEBP1 mRNA levels. CELF1-mediated PEBP1 suppression activates MAPK signaling (Raf1, TAK1, ERK1/2, p38) and promotes cardiac hypertrophy. RNA immunoprecipitation (RIP), biotin RNA pull-down, dual-luciferase assay, CELF1 overexpression/depletion, TAC cardiac hypertrophy mouse model Cell and tissue research Medium 34669021
2015 RKIP negatively regulates MMP13 expression through the Erk2 signaling pathway in a transcription factor AP-1-independent manner, thereby inhibiting local breast cancer cell invasion. Loss/gain-of-function experiments show MMP13 as the causal downstream effector of RKIP-mediated invasion suppression. PCR-based screening, DNA microarray analysis, loss/gain-of-function (RKIP, MMP13), invasion assays, Erk2 pathway analysis PloS one Medium 26308852

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2017 PEBP1 Wardens Ferroptosis by Enabling Lipoxygenase Generation of Lipid Death Signals. Cell 771 29053969
1999 Suppression of Raf-1 kinase activity and MAP kinase signalling by RKIP. Nature 723 10490027
2011 Evolution of the PEBP gene family in plants: functional diversification in seed plant evolution. Plant physiology 212 21642442
2007 A genomic and expression compendium of the expanded PEBP gene family from maize. Plant physiology 206 17993543
2004 RKIP sensitizes prostate and breast cancer cells to drug-induced apoptosis. The Journal of biological chemistry 201 14766752
2011 Signalling pathway for RKIP and Let-7 regulates and predicts metastatic breast cancer. The EMBO journal 178 21873975
2005 Phylogenomic analysis of the PEBP gene family in cereals. Journal of molecular evolution 169 16170456
2004 The role of Raf kinase inhibitor protein (RKIP) in health and disease. Biochemical pharmacology 141 15313400
2020 Resolving the paradox of ferroptotic cell death: Ferrostatin-1 binds to 15LOX/PEBP1 complex, suppresses generation of peroxidized ETE-PE, and protects against ferroptosis. Redox biology 116 33126055
2011 Raf kinase inhibitor protein RKIP enhances signaling by glycogen synthase kinase-3β. Cancer research 108 21303975
2005 RKIP downregulates B-Raf kinase activity in melanoma cancer cells. Oncogene 107 15782137
2008 Raf kinase inhibitory protein (RKIP): a physiological regulator and future therapeutic target. Expert opinion on therapeutic targets 100 18781826
2020 PEBP1 acts as a rheostat between prosurvival autophagy and ferroptotic death in asthmatic epithelial cells. Proceedings of the National Academy of Sciences of the United States of America 93 32513718
2013 RKIP: much more than Raf kinase inhibitory protein. Journal of cellular physiology 90 23359513
2013 RKIP and HMGA2 regulate breast tumor survival and metastasis through lysyl oxidase and syndecan-2. Oncogene 81 23975428
2016 Revisiting the phosphatidylethanolamine-binding protein (PEBP) gene family reveals cryptic FLOWERING LOCUS T gene homologs in gymnosperms and sheds new light on functional evolution. The New phytologist 70 27375201
2012 Raf kinase inhibitor protein (RKIP) in cancer. Cancer metastasis reviews 69 22684368
2022 Circular RNA circPOLR2A promotes clear cell renal cell carcinoma progression by facilitating the UBE3C-induced ubiquitination of PEBP1 and, thereby, activating the ERK signaling pathway. Molecular cancer 61 35840930
2002 The crystal structure of PEBP-2, a homologue of the PEBP/RKIP family. Acta crystallographica. Section D, Biological crystallography 59 12037323
2020 Bmi-1-induced miR-27a and miR-155 promote tumor metastasis and chemoresistance by targeting RKIP in gastric cancer. Molecular cancer 58 32580736
2012 Raf kinase inhibitor RKIP inhibits MDA-9/syntenin-mediated metastasis in melanoma. Cancer research 56 23066033
2018 RKIP: A Key Regulator in Tumor Metastasis Initiation and Resistance to Apoptosis: Therapeutic Targeting and Impact. Cancers 55 30149591
2014 CDK5-mediated phosphorylation and autophagy of RKIP regulate neuronal death in Parkinson's disease. Neurobiology of aging 54 25104559
2004 Metastasis suppressor genes: a role for raf kinase inhibitor protein (RKIP). Anti-cancer drugs 49 15269597
2018 RIPK4/PEBP1 axis promotes pancreatic cancer cell migration and invasion by activating RAF1/MEK/ERK signaling. International journal of oncology 48 29436617
2011 Association of CRISP2, CCT8, PEBP1 mRNA abundance in sperm and sire conception rate in Holstein bulls. Theriogenology 48 21529916
2010 RAF kinase inhibitory protein (RKIP) modulates cell cycle kinetics and motility. Molecular bioSystems 47 21180766
2016 RKIP suppresses the proliferation and metastasis of breast cancer cell lines through up-regulation of miR-185 targeting HMGA2. Archives of biochemistry and biophysics 46 27651238
2016 PEBP1, a RAF kinase inhibitory protein, negatively regulates starvation-induced autophagy by direct interaction with LC3. Autophagy 45 27540684
2014 Raf kinase inhibitory protein (RKIP) as a metastasis suppressor: regulation of signaling networks in cancer. Critical reviews in oncogenesis 45 25597354
2015 RKIP regulates CCL5 expression to inhibit breast cancer invasion and metastasis by controlling macrophage infiltration. Oncotarget 43 26375811
2022 PEBP balances apoptosis and autophagy in whitefly upon arbovirus infection. Nature communications 41 35149691
2014 RKIP-mediated chemo-immunosensitization of resistant cancer cells via disruption of the NF-κB/Snail/YY1/RKIP resistance-driver loop. Critical reviews in oncogenesis 38 25597353
2022 Inactivation of RIP3 kinase sensitizes to 15LOX/PEBP1-mediated ferroptotic death. Redox biology 37 35101798
2016 Understanding perspectives of signalling mechanisms regulating PEBP1 function. Cell biochemistry and function 37 27385268
2014 Survey of Raf kinase inhibitor protein (RKIP) in multiple cancer types. Critical reviews in oncogenesis 37 25597355
2013 Geographic analysis of RKIP expression and its clinical relevance in colorectal cancer. British journal of cancer 37 23632477
2020 The inhibitor effect of RKIP on inflammasome activation and inflammasome-dependent diseases. Cellular & molecular immunology 36 32901127
2018 Mobility of Antiflorigen and PEBP mRNAs in Tomato-Tobacco Heterografts. Plant physiology 36 30150303
2012 RKIP expression associated with gastric cancer cell invasion and metastasis. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 36 22246605
2013 Overexpression of RKIP inhibits cell invasion in glioma cell lines through upregulation of miR-98. BioMed research international 35 24392454
2020 PEBP1 suppresses HIV transcription and induces latency by inactivating MAPK/NF-κB signaling. EMBO reports 34 32924251
2009 BRAF and RKIP are significantly decreased in cutaneous squamous cell carcinoma. Cell cycle (Georgetown, Tex.) 34 19342899
2019 Current Status of Raf Kinase Inhibitor Protein (RKIP) in Lung Cancer: Behind RTK Signaling. Cells 33 31083461
2022 Activation of RKIP Binding ASC Attenuates Neuronal Pyroptosis and Brain Injury via Caspase-1/GSDMD Signaling Pathway After Intracerebral Hemorrhage in Mice. Translational stroke research 32 35355228
2019 RKIP as an Inflammatory and Immune System Modulator: Implications in Cancer. Biomolecules 32 31766768
2015 Reduction of RKIP expression promotes nasopharyngeal carcinoma invasion and metastasis by activating Stat3 signaling. Oncotarget 32 25915430
2015 The biological complexity of RKIP signaling in human cancers. Experimental & molecular medicine 31 26403261
2013 Cigarette smoking exposure alters pebp1 DNA methylation and protein profile involved in MAPK signaling pathway in mice testis. Biology of reproduction 31 24198121
2012 Transcriptional regulation of RKIP expression by androgen in prostate cells. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 31 23095933
2017 Overexpression of RKIP and its cross-talk with several regulatory gene products in multiple myeloma. Journal of experimental & clinical cancer research : CR 29 28476134
2009 Characterization of human and bovine phosphatidylethanolamine-binding protein (PEBP/RKIP) interactions with morphine and morphine-glucuronides determined by noncovalent mass spectrometry. Medical science monitor : international medical journal of experimental and clinical research 29 19564817
2014 Correlation of RKIP, STAT3 and cyclin D1 expression in pathogenesis of gastric cancer. International journal of clinical and experimental pathology 28 25337233
2010 Characterization of the Raf kinase inhibitory protein (RKIP) binding pocket: NMR-based screening identifies small-molecule ligands. PloS one 28 20463977
2020 Circular RNA MTO1 suppresses tumorigenesis of gastric carcinoma by sponging miR-3200-5p and targeting PEBP1. Molecular and cellular probes 27 32194149
2016 Characterization and Functional Analysis of PEBP Family Genes in Upland Cotton (Gossypium hirsutum L.). PloS one 27 27552108
2024 Lipid peroxidation-induced ferroptosis as a therapeutic target for mitigating neuronal injury and inflammation in sepsis-associated encephalopathy: insights into the hippocampal PEBP-1/15-LOX/GPX4 pathway. Lipids in health and disease 26 38685023
2022 The Role of RKIP in the Regulation of EMT in the Tumor Microenvironment. Cancers 26 36230521
2018 Tulipa gesneriana and Lilium longiflorum PEBP Genes and Their Putative Roles in Flowering Time Control. Plant & cell physiology 26 29088399
2018 RKIP mediates autoimmune inflammation by positively regulating IL-17R signaling. EMBO reports 26 29674348
2015 RKIP Inhibits Local Breast Cancer Invasion by Antagonizing the Transcriptional Activation of MMP13. PloS one 26 26308852
2010 Viral infection and cancer: the NF-kappaB/Snail/RKIP loop regulates target cell sensitivity to apoptosis by cytotoxic lymphocytes. Critical reviews in immunology 26 20370618
2024 Semaglutide protects against diabetes-associated cardiac inflammation via Sirt3-dependent RKIP pathway. British journal of pharmacology 23 39710830
2023 Genome-Wide Identification of PEBP Gene Family in Solanum lycopersicum. International journal of molecular sciences 23 37298136
2014 RKIP structure drives its function: a three-state model for regulation of RKIP. Critical reviews in oncogenesis 22 25597357
2014 Raf kinase inhibitory protein (RKIP): functional pleiotropy in the mammalian brain. Critical reviews in oncogenesis 22 25597360
2012 Ligand binding study of human PEBP1/RKIP: interaction with nucleotides and Raf-1 peptides evidenced by NMR and mass spectrometry. PloS one 22 22558375
2006 Identification and characterization of PEBP as a calpain substrate. Journal of neurochemistry 22 17018026
2024 Relationship of Signaling Pathways between RKIP Expression and the Inhibition of EMT-Inducing Transcription Factors SNAIL1/2, TWIST1/2 and ZEB1/2. Cancers 21 39335152
2023 Discovering selective antiferroptotic inhibitors of the 15LOX/PEBP1 complex noninterfering with biosynthesis of lipid mediators. Proceedings of the National Academy of Sciences of the United States of America 21 37327313
2021 RKIP Pleiotropic Activities in Cancer and Inflammatory Diseases: Role in Immunity. Cancers 21 34944867
2018 Linking Autophagy and the Dysregulated NFκB/ SNAIL/YY1/RKIP/PTEN Loop in Cancer: Therapeutic Implications. Critical reviews in oncogenesis 21 30311562
2024 XJB-5-131 protects chondrocytes from ferroptosis to alleviate osteoarthritis progression via restoring Pebp1 expression. Journal of orthopaedic translation 20 38304614
2009 Downregulation of PEBP1 in rat brain cortex in hypoxia. Journal of molecular neuroscience : MN 20 19705086
2023 Cross-Talks between RKIP and YY1 through a Multilevel Bioinformatics Pan-Cancer Analysis. Cancers 19 37894300
2021 Genome-wide characterization of PEBP family genes in nine Rosaceae tree species and their expression analysis in P. mume. BMC ecology and evolution 19 33622244
2020 PEBP1/RKIP behavior: a mirror of actin-membrane organization. Cellular and molecular life sciences : CMLS 19 31960115
2020 Genome-wide member identification, phylogeny and expression analysis of PEBP gene family in wheat and its progenitors. PeerJ 19 33362967
2014 Clinical significance of RKIP mRNA expression in non-small cell lung cancer. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 19 24420151
2014 RKIP suppresses gastric cancer cell proliferation and invasion and enhances apoptosis regulated by microRNA-224. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 19 25017365
2021 The RhoA dependent anti-metastatic function of RKIP in breast cancer. Scientific reports 18 34465801
2020 cMET promotes metastasis and epithelial-mesenchymal transition in colorectal carcinoma by repressing RKIP. Journal of cellular physiology 18 33151569
2022 Understanding Mechanisms of RKIP Regulation to Improve the Development of New Diagnostic Tools. Cancers 17 36291854
2018 Identification and expression analysis of phosphatidy ethanolamine-binding protein (PEBP) gene family in cotton. Genomics 17 30244142
2014 RKIP: a governor of intracellular signaling. Critical reviews in oncogenesis 17 25597358
2013 Raf kinase inhibitor protein (RKIP) and phospho-RKIP expression in melanomas. Acta histochemica 17 23601922
2023 Cancer resistance via the downregulation of the tumor suppressors RKIP and PTEN expressions: therapeutic implications. Exploration of targeted anti-tumor therapy 16 37205308
2023 AR/RKIP pathway mediates the inhibitory effects of icariin on renal fibrosis and endothelial-to-mesenchymal transition in type 2 diabetic nephropathy. Journal of ethnopharmacology 16 37977422
2022 Analysis of the PEBP gene family and identification of a novel FLOWERING LOCUS T orthologue in sugarcane. Journal of experimental botany 16 34893811
2022 Genome-wide identification of PEBP gene family members in potato, their phylogenetic relationships, and expression patterns under heat stress. Molecular biology reports 16 35366758
2021 RNA-binding protein CELF1 promotes cardiac hypertrophy via interaction with PEBP1 in cardiomyocytes. Cell and tissue research 16 34669021
2019 Identification and Characterization of the PEBP Family Genes in Moso Bamboo (Phyllostachys heterocycla). Scientific reports 16 31628413
2017 RKIP reduction enhances radioresistance by activating the Shh signaling pathway in non-small-cell lung cancer. OncoTargets and therapy 16 29200875
2023 Membrane regulation of 15LOX-1/PEBP1 complex prompts the generation of ferroptotic signals, oxygenated PEs. Free radical biology & medicine 15 37678654
2022 Low expression of PEBP1P2 promotes metastasis of clear cell renal cell carcinoma by post-transcriptional regulation of PEBP1 and KLF13 mRNA. Experimental hematology & oncology 15 36348434
2021 A Functional Network Model of the Metastasis Suppressor PEBP1/RKIP and Its Regulators in Breast Cancer Cells. Cancers 15 34885208
2020 Resveratrol binds and activates RKIP protein in colorectal cancer. Amino acids 14 32918615
2014 Expression of Raf Kinase Inhibitor Protein (RKIP) is a predictor of uveal melanoma metastasis. Histology and histopathology 14 24763848
2022 Florigen and its homologs of FT/CETS/PEBP/RKIP/YbhB family may be the enzymes of small molecule metabolism: review of the evidence. BMC plant biology 13 35086479
2022 The RAF Kinase Inhibitor Protein (RKIP): Good as Tumour Suppressor, Bad for the Heart. Cells 13 35203304

Missed literature

Know a paper Affinage missed for PEBP1? Flag it for the maintainers and the community.

No submissions yet.