Affinage

PEBP1

Phosphatidylethanolamine-binding protein 1 · UniProt P30086

Length
187 aa
Mass
21.1 kDa
Annotated
2026-04-29
100 papers in source corpus 24 papers cited in narrative 24 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PEBP1 (also known as RKIP) is a phospholipid-binding scaffold protein that controls cell fate decisions by toggling between distinct binding partners in a phosphorylation-dependent manner. It complexes with 15-lipoxygenase isoforms to redirect their substrate specificity from free polyunsaturated fatty acids to esterified phosphatidylethanolamines, generating hydroperoxy-PE signals that execute ferroptosis when GPX4 activity is insufficient (PMID:29053969, PMID:37678654); competition between 15LOX and RIP3 for PEBP1 binding determines whether cells undergo ferroptosis or necroptosis (PMID:35101798). Independently, PEBP1 inhibits the Raf/MEK/ERK and NF-κB signaling cascades by directly binding Raf-1 and B-Raf kinases, functioning as a metastasis suppressor whose loss activates ERK-dependent proliferative and invasive programs (PMID:15782137, PMID:32924251). PEBP1 also directly binds LC3 via a LIR motif to suppress autophagy through AKT-MTORC1 activation, a constraint relieved by Ser153 phosphorylation, and binds ASC to competitively block NLRP3/NLRC4 inflammasome assembly (PMID:27540684, PMID:32901127).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 2005 High

    Extending PEBP1's known inhibition of Raf-1, the demonstration that it also directly binds and antagonizes B-Raf established PEBP1 as a general MAP kinase pathway inhibitor relevant to oncogenic B-Raf signaling in melanoma.

    Evidence Yeast two-hybrid, co-IP, and kinase assays in melanoma cells

    PMID:15782137

    Open questions at the time
    • Structural basis of PEBP1–B-Raf interaction not resolved
    • Whether PEBP1 inhibits other Raf family members was not tested
  2. 2006 Medium

    Identification of PEBP1 as a calpain substrate and partial proteasome inhibitor revealed that PEBP1 levels are themselves actively regulated by proteolytic systems.

    Evidence In vitro calpain cleavage assay, brain injury model, proteasome activity assay

    PMID:17018026

    Open questions at the time
    • Physiological significance of 30% proteasome inhibition unclear
    • Calpain cleavage site not mapped
  3. 2010 High

    NMR characterization of PEBP1's conserved ligand-binding pocket showed that phospholipid occupancy and Ser153 phosphorylation are competing regulatory inputs controlling Raf-1 interaction, providing a structural basis for PEBP1's partner-switching behavior.

    Evidence Heteronuclear NMR spectroscopy with ligand binding and phosphorylation assays

    PMID:20463977

    Open questions at the time
    • In vivo confirmation that pocket occupancy regulates partner switching not demonstrated
    • Full-length complex structures not available
  4. 2012 High

    Two discoveries broadened PEBP1's regulatory context: androgen receptor was shown to transcriptionally activate PEBP1 via a promoter ARE, and PEBP1 was found to physically interact with MDA-9/syntenin to suppress FAK/Src metastatic signaling.

    Evidence ChIP and EMSA for AR binding; co-IP plus in vivo dissemination model for MDA-9 interaction

    PMID:23066033 PMID:23095933

    Open questions at the time
    • Whether AR-dependent PEBP1 regulation is disrupted in castration-resistant prostate cancer not tested
    • MDA-9 interaction domain on PEBP1 not mapped
  5. 2014 High

    CDK5-mediated phosphorylation at T42 was shown to release Raf-1 and expose a CMA-targeting motif, providing the first mechanism for signal-dependent PEBP1 degradation and linking PEBP1 loss to ERK overactivation in Parkinson's disease neurodegeneration.

    Evidence In vitro kinase assay, mutagenesis, Hsc70 co-IP, CMA degradation assay in PD models and patient brain samples

    PMID:25104559

    Open questions at the time
    • Whether blocking T42 phosphorylation is neuroprotective in vivo not demonstrated
    • Other kinases targeting T42 not excluded
  6. 2016 High

    Discovery that PEBP1 contains a functional LIR motif and directly binds LC3 to inhibit autophagy via AKT-MTORC1 activation established PEBP1 as a negative regulator of autophagy, with Ser153 phosphorylation serving as the release switch.

    Evidence Co-IP, LIR motif mutagenesis (WXXL→AXXA), autophagy flux assays

    PMID:27540684

    Open questions at the time
    • Kinase(s) responsible for Ser153 phosphorylation in this context not identified
    • Whether LC3 and Raf-1 binding are mutually exclusive not tested
  7. 2017 High

    The foundational discovery that PEBP1 complexes with 15-lipoxygenases to switch their substrate from free PUFAs to membrane phosphatidylethanolamine established the molecular mechanism of ferroptotic death signal generation.

    Evidence Co-IP, lipidomics, cell-based ferroptosis assays across multiple cell types and disease models

    PMID:29053969

    Open questions at the time
    • Structural basis of how PEBP1 alters 15LOX substrate access not resolved at this point
    • Tissue specificity of the 15LOX/PEBP1 complex not explored
  8. 2020 High

    Three parallel advances defined PEBP1 as a multimodal cell-fate regulator: Fer-1 was shown to specifically target the 15LOX/PEBP1 complex rather than 15LOX alone; the ferroptotic product 15-HpETE-PE was found to stimulate LC3-I lipidation linking ferroptosis to autophagy; and PEBP1 was identified as a host factor maintaining HIV latency via NF-κB cytoplasmic sequestration.

    Evidence Biochemical inhibition and computational modeling across nine ferroptosis models; co-IP/lipidomics in patient HAECs; genome-wide CRISPR screen plus primary CD4+ T cells from ART patients

    PMID:32513718 PMID:32924251 PMID:33126055

    Open questions at the time
    • Whether Fer-1 has clinical utility at the 15LOX/PEBP1 complex in vivo remains unclear
    • Mechanism by which 15-HpETE-PE promotes LC3-I lipidation not fully elucidated
  9. 2020 High

    PEBP1 was shown to directly bind ASC and competitively block NLR protein recruitment, establishing a role as an endogenous inflammasome assembly inhibitor.

    Evidence Co-IP, competition assays in macrophages and THP-1 cells, in vivo mouse inflammasome disease models

    PMID:32901127

    Open questions at the time
    • Binding interface between PEBP1 and ASC not structurally defined
    • Whether PEBP1 regulates non-canonical inflammasomes not tested
  10. 2022 High

    Identification of RIP3 as a competitive PEBP1-binding partner showed that relative 15LOX/RIP3 expression levels determine whether PEBP1 drives ferroptosis or suppresses necroptosis, establishing PEBP1 as a cell-death mode switch.

    Evidence Genetic Rip3K51A/K51A mice, co-IP, redox lipidomics, computational modeling, in vivo brain trauma models

    PMID:35101798

    Open questions at the time
    • Quantitative binding affinities of PEBP1 for RIP3 versus 15LOX not measured biochemically
    • Whether other RIPK family members compete for PEBP1 not examined
  11. 2023 High

    Molecular dynamics simulations combined with mutagenesis revealed how PEBP1 binding to membrane-associated 15LOX-1 induces conformational changes granting SAPE substrate access, and enabled design of selective ferroptosis inhibitors (FerroLOXINs) targeting the catalytic complex.

    Evidence Computational MD simulation, LC-MS lipidomics, P112E mutagenesis, custom compound screening in vitro and in vivo

    PMID:37327313 PMID:37678654

    Open questions at the time
    • No high-resolution experimental structure of the 15LOX/PEBP1 complex available
    • FerroLOXIN pharmacokinetics and therapeutic window in disease models not established

Open questions

Synthesis pass · forward-looking unresolved questions
  • How PEBP1 simultaneously integrates signals from its multiple partners (15LOX, RIP3, Raf-1, LC3, ASC, STAT3) in a single cell — particularly the quantitative rules governing partner selection beyond expression level — remains unresolved.
  • No high-resolution experimental structure of any PEBP1–partner complex
  • Quantitative, cell-type-specific partner occupancy model lacking
  • In vivo genetic separation-of-function mutants for individual PEBP1 interactions not generated

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 5 GO:0008289 lipid binding 3 GO:0060090 molecular adaptor activity 3
Localization
GO:0005829 cytosol 2 GO:0005886 plasma membrane 1
Pathway
R-HSA-162582 Signal Transduction 5 R-HSA-5357801 Programmed Cell Death 3 R-HSA-1430728 Metabolism 2 R-HSA-9612973 Autophagy 2 R-HSA-168256 Immune System 1
Partners
ALOX15ALOX15BBRAFMAP1LC3BPYCARDRAF1RIPK3STAT3
Complex memberships
15LOX/PEBP1 ferroptotic complex

Evidence

Reading pass · 24 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2017 PEBP1 complexes with 15-lipoxygenase isoforms 15LO1 and 15LO2, changing their substrate competence from free polyunsaturated fatty acids to phosphatidylethanolamine (PE), enabling generation of hydroperoxy-PE (ferroptotic death signals). Insufficient GPX4 activity to reduce these hydroperoxy-PEs leads to ferroptosis. Co-immunoprecipitation, lipidomics, cell-based ferroptosis assays in multiple cell types, genetic manipulation Cell High 29053969
2020 Ferrostatin-1 (Fer-1) does not inhibit 15LOX alone but effectively inhibits HpETE-PE production by the 15LOX/PEBP1 complex; computational modeling shows Fer-1 binds to the 15LOX/PEBP1 complex at three sites and disrupts allosteric motions required for catalysis. Biochemical inhibition assays, computational molecular modeling, redox lipidomics in nine ferroptosis models Redox biology High 33126055
2020 PEBP1 acts as a rheostat between ferroptosis and autophagy: it interacts with both 15LO1 (proferroptotic) and the autophagic protein LC3, and the 15LO1-PEBP1-generated ferroptotic phospholipid 15-HpETE-PE promotes LC3-I lipidation to stimulate autophagy, which protects cells from ferroptotic death. Co-immunoprecipitation, lipid mass spectrometry, genetic knockdown/overexpression, patient HAEC samples Proceedings of the National Academy of Sciences of the United States of America High 32513718
2016 PEBP1 contains a functional LC3-interacting region (LIR) motif (WXXL) and directly binds PE-unconjugated LC3 in cells. PEBP1 overexpression inhibits starvation-induced autophagy by activating AKT-MTORC1 signaling and suppressing ULK1 activity. Phosphorylation of PEBP1 at Ser153 dissociates LC3 from the PEBP1-LC3 complex, triggering autophagy induction. Co-immunoprecipitation, LIR motif mutagenesis (WXXL→AXXA), autophagy flux assays, kinase signaling analysis Autophagy High 27540684
2022 PEBP1 complexes with RIP3 kinase and inhibits necroptosis. When 15LOX is elevated, its higher affinity enables it to sequester PEBP1 from RIP3, shifting cell death from necroptosis to ferroptosis via PUFA-PE oxidation; PEBP1 thus acts as a necroptosis-to-ferroptosis switch. Genetic (Rip3K51A/K51A mice), biochemical co-IP, redox lipidomics, computational modeling, in vivo irradiation and brain trauma models Redox biology High 35101798
2023 Membrane association of the 15LOX-1/PEBP1 complex triggers a conformational change that facilitates access of SAPE substrates to the catalytic site; PEBP1 binding promotes tight interactions and induces further conformational changes enabling oxidation of SAPE to 15-HpETE-PE and 12-HpETE-PE. PEBP1 P112E mutation significantly affects ferroptotic signal generation. Computational molecular dynamics simulation, liquid chromatography-mass spectrometry, mutagenesis Free radical biology & medicine High 37678654
2023 Two lead compounds FerroLOXIN-1 and FerroLOXIN-2 selectively inhibit ferroptosis by targeting the 15LOX-2/PEBP1 catalytic complex: one alters the binding pose of ETE-PE in a non-productive way, the other blocks the predominant oxygen channel, preventing ETE-PE peroxidation, without affecting biosynthesis of lipid mediators. Biochemical assays with custom compound library, redox lipidomics, computational analysis, in vitro and in vivo ferroptosis models Proceedings of the National Academy of Sciences of the United States of America High 37327313
2005 RKIP (PEBP1) specifically interacts with B-Raf (in addition to Raf-1) and antagonizes B-Raf kinase activity; ectopic RKIP expression partially reverted B-Raf kinase-transformed melanoma cells. Effects on B-Raf were shown to be independent of RKIP's known inhibitory action on Raf-1. Yeast two-hybrid, co-immunoprecipitation, kinase activity assays, cell transformation assays Oncogene High 15782137
2014 PEBP1 is a substrate of CDK5 in neurons; CDK5 phosphorylates PEBP1 at T42, causing release of Raf-1. T42 phosphorylation exposes the C-terminal motif 'KLYEQ', recognized by chaperone Hsc70, leading to chaperone-mediated autophagy (CMA) degradation of PEBP1, resulting in ERK/MAPK overactivation and neuronal death in Parkinson's disease models. In vitro kinase assay, mutagenesis, co-immunoprecipitation with Hsc70, CMA degradation assay, PD patient brain samples and animal models Neurobiology of aging High 25104559
2020 PEBP1 induces HIV latency by de-phosphorylating Raf1/ERK/IκB and IKK/IκB signaling pathways to sequester NF-κB in the cytoplasm, transcriptionally inactivating HIV-1. PEBP1 depletion reactivates HIV-1 in multiple latency models. Genome-wide CRISPR-Cas9 knockout screen, pathway signaling analysis, NF-κB nuclear translocation assays, primary CD4+ T cells from ART patients EMBO reports High 32924251
2020 RKIP (PEBP1) directly binds to ASC (apoptosis-associated speck-like protein containing a CARD) and competes with NLRP1, NLRP3, or NLRC4 to interact with ASC, thereby interrupting inflammasome assembly and activation. Co-immunoprecipitation, overexpression/knockdown in macrophages and THP-1 cells, in vivo mouse models of inflammasome-related disease Cellular & molecular immunology High 32901127
2022 CircPOLR2A interacts with both UBE3C and PEBP1, facilitating UBE3C-mediated ubiquitination and proteasomal degradation of PEBP1 protein; loss of PEBP1 activates the ERK signaling pathway to promote renal cell carcinoma progression. RNA pull-down, mass spectrometry, RIP, FISH, Co-IP, ubiquitination assay, rescue experiments Molecular cancer High 35840930
2021 Dihydroartemisinin (DHA) induces ferroptosis in HCC cells by promoting the formation of the PEBP1/15-LO complex and lipid peroxidation; DHA upregulates PEBP1 protein expression by inhibiting its ubiquitination degradation, without directly affecting 15-LO expression. Western blot, ferroptosis marker assays, PEBP1 knockdown rescue, ubiquitination assays, in vivo tumor models Oxidative medicine and cellular longevity Medium 34925691
2018 RIPK4 promotes pancreatic cancer cell migration and invasion via the RAF1/MEK/ERK pathway by inducing proteasome-mediated degradation of PEBP1; suppression of PEBP1 degradation eliminates RIPK4-induced RAF1/MEK/ERK activation. High-throughput screening, knockdown/overexpression, pathway inhibitor experiments, proteasome inhibition rescue International journal of oncology Medium 29436617
2012 RKIP physically interacts with MDA-9/syntenin and suppresses FAK and c-Src phosphorylation; MDA-9 transcriptionally downregulates RKIP expression, and ectopic RKIP overrides MDA-9-mediated FAK/c-Src complex formation and metastatic signaling. Co-immunoprecipitation, tumor array, kinase phosphorylation assays, in vivo tumor dissemination model Cancer research Medium 23066033
2006 PEBP1 is a substrate of calpain both in vitro and in situ, confirmed in a brain injury model where calpain is activated; PEBP1 also inhibits the chymotrypsin-like activity of the proteasome by approximately 30%. In vitro proteomics calpain cleavage assay, brain injury model (in situ validation), proteasome activity assay Journal of neurochemistry Medium 17018026
2010 RKIP's conserved ligand-binding pocket binds phospholipid DHPE, and occupation of this pocket or phosphorylation at Ser-153 regulate RKIP's interaction with Raf-1. NMR screening identified three novel ligands binding to the RKIP pocket, with distinct properties from DHPE. Heteronuclear NMR spectroscopy, ligand binding assays, phosphorylation assays PloS one High 20463977
2014 RKIP structural analysis identifies an allosteric mechanism with three functional states: (1) binding and inhibiting Raf-1, (2) after Ser-153 phosphorylation, binding and inhibiting GRK2, and (3) a third state facilitating RKIP phosphorylation; pocket loop dynamics control transitions between these states. Structural analysis (review of crystal structures combined with functional data), phosphorylation assays Critical reviews in oncogenesis Medium 25597357
2021 RKIP inhibits breast cancer cell invasion by stimulating RhoA anti-tumorigenic functions in an ERK2 and GEF-H1 dependent manner, enhancing E-cadherin membrane localization and inhibiting CCL5 expression. Knockdown/overexpression, RhoA activity assays, E-cadherin localization by imaging, CCL5 measurement Scientific reports Medium 34465801
2012 RKIP transcription is positively regulated by androgen/androgen receptor (AR): DHT increases RKIP promoter activity, AR binds to a putative androgen response element (ARE) in the RKIP promoter (validated by EMSA and ChIP), and castration reduces RKIP expression in mouse prostate in vivo. RT-PCR, Western blot, luciferase reporter assay, EMSA, ChIP assay, in vivo castration model Cellular physiology and biochemistry High 23095933
2021 CELF1 RNA-binding protein directly binds to the 3'UTR fragment 1 of PEBP1 mRNA (shown by RNA immunoprecipitation and biotin pull-down), reducing PEBP1 protein expression post-transcriptionally without altering PEBP1 mRNA levels; CELF1-mediated PEBP1 reduction activates MAPK signaling (Raf1, TAK1, ERK1/2, p38) promoting cardiac hypertrophy. RNA immunoprecipitation (RIP), biotin pull-down, dual-luciferase assay, Western blot, in vivo cardiac hypertrophy model (TAC) Cell and tissue research High 34669021
2015 RKIP negatively regulates CCL5 expression in breast cancer cells, thereby limiting tumor macrophage infiltration and inhibiting angiogenesis; in mouse allograft models, ectopic RKIP expression decreased tumor vasculature, macrophage infiltration, and lung metastases through CCL5 suppression. Loss- and gain-of-function approaches, in vivo mouse allograft model, CCL5 rescue experiments Oncotarget Medium 26375811
2015 RKIP reduces STAT3 phosphorylation in NPC cells by directly interacting with STAT3; RKIP overexpression attenuates and RKIP knockdown enhances STAT3 activation, promoting NPC invasion, metastasis, and EMT through STAT3 pathway activation. Co-immunoprecipitation, gain- and loss-of-function, STAT3 phosphorylation assays, in vivo xenograft metastasis model Oncotarget Medium 25915430
2024 XJB-5-131 protects chondrocytes from ferroptosis via restoring PEBP1 expression; the anti-ferroptotic effects of XJB-5-131 were abolished by the PEBP1 antagonist Locostatin, identifying PEBP1 as the functional downstream target. RNA sequencing and DMM surgical OA models were used. RNA sequencing, PEBP1 antagonist (Locostatin), in vitro ferroptosis assays, in vivo DMM mouse model, intra-articular injection Journal of orthopaedic translation Medium 38304614

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 758 29053969
2011 Evolution of the PEBP gene family in plants: functional diversification in seed plant evolution. Plant physiology 209 21642442
2004 RKIP sensitizes prostate and breast cancer cells to drug-induced apoptosis. The Journal of biological chemistry 201 14766752
2005 Phylogenomic analysis of the PEBP gene family in cereals. Journal of molecular evolution 169 16170456
1993 blaI and blaR1 regulate beta-lactamase and PBP 2a production in methicillin-resistant Staphylococcus aureus. Antimicrobial agents and chemotherapy 134 8517704
1992 Membrane intermediates in the peptidoglycan metabolism of Escherichia coli: possible roles of PBP 1b and PBP 3. Journal of bacteriology 129 1592809
2010 The Role of B-RAF Mutations in Melanoma and the Induction of EMT via Dysregulation of the NF-κB/Snail/RKIP/PTEN Circuit. Genes & cancer 115 20827424
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 112 33126055
2010 Dual role of NO donors in the reversal of tumor cell resistance and EMT: Downregulation of the NF-κB/Snail/YY1/RKIP circuitry. Nitric oxide : biology and chemistry 109 20933602
2009 Molecular and functional characterization of PEBP genes in barley reveal the diversification of their roles in flowering. Plant physiology 108 19168644
2005 RKIP downregulates B-Raf kinase activity in melanoma cancer cells. Oncogene 107 15782137
2000 Hippocampal cholinergic neurostimulating peptides (HCNP). Progress in neurobiology 102 10622376
2013 RKIP: much more than Raf kinase inhibitory protein. Journal of cellular physiology 90 23359513
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 89 32513718
2017 MiR-543 Promotes Proliferation and Epithelial-Mesenchymal Transition in Prostate Cancer via Targeting RKIP. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 81 28245474
2008 Structural basis of the honey bee PBP pheromone and pH-induced conformational change. Journal of molecular biology 71 18508083
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 59 35840930
2018 KRAS promotes tumor metastasis and chemoresistance by repressing RKIP via the MAPK-ERK pathway in pancreatic cancer. International journal of cancer 59 29315556
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 57 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 52 25104559
2004 Metastasis suppressor genes: a role for raf kinase inhibitor protein (RKIP). Anti-cancer drugs 49 15269597
2011 Association of CRISP2, CCT8, PEBP1 mRNA abundance in sperm and sire conception rate in Holstein bulls. Theriogenology 48 21529916
2018 RIPK4/PEBP1 axis promotes pancreatic cancer cell migration and invasion by activating RAF1/MEK/ERK signaling. International journal of oncology 46 29436617
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
2014 Raf kinase inhibitory protein (RKIP) as a metastasis suppressor: regulation of signaling networks in cancer. Critical reviews in oncogenesis 45 25597354
2016 PEBP1, a RAF kinase inhibitory protein, negatively regulates starvation-induced autophagy by direct interaction with LC3. Autophagy 44 27540684
2021 Dihydroartemisinin Induces Ferroptosis in HCC by Promoting the Formation of PEBP1/15-LO. Oxidative medicine and cellular longevity 43 34925691
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 40 35149691
2017 Inverse correlation between the metastasis suppressor RKIP and the metastasis inducer YY1: Contrasting roles in the regulation of chemo/immuno-resistance in cancer. Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy 38 28363333
2022 Inactivation of RIP3 kinase sensitizes to 15LOX/PEBP1-mediated ferroptotic death. Redox biology 37 35101798
2019 Structural Basis for E. coli Penicillin Binding Protein (PBP) 2 Inhibition, a Platform for Drug Design. Journal of medicinal chemistry 37 30995398
2016 Understanding perspectives of signalling mechanisms regulating PEBP1 function. Cell biochemistry and function 37 27385268
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 37 25597353
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
2018 Mobility of Antiflorigen and PEBP mRNAs in Tomato-Tobacco Heterografts. Plant physiology 36 30150303
2020 The inhibitor effect of RKIP on inflammasome activation and inflammasome-dependent diseases. Cellular & molecular immunology 35 32901127
2013 Overexpression of RKIP inhibits cell invasion in glioma cell lines through upregulation of miR-98. BioMed research international 35 24392454
2009 BRAF and RKIP are significantly decreased in cutaneous squamous cell carcinoma. Cell cycle (Georgetown, Tex.) 34 19342899
2020 PEBP1 suppresses HIV transcription and induces latency by inactivating MAPK/NF-κB signaling. EMBO reports 33 32924251
2019 Current Status of Raf Kinase Inhibitor Protein (RKIP) in Lung Cancer: Behind RTK Signaling. Cells 33 31083461
2019 RKIP as an Inflammatory and Immune System Modulator: Implications in Cancer. Biomolecules 32 31766768
2010 Implication of RAF and RKIP genes in urinary bladder cancer. Pathology oncology research : POR 32 20853079
1995 Accumulation of hippocampal cholinergic neurostimulating peptide (HCNP)-related components in Hirano bodies. Neuropathology and applied neurobiology 32 7770119
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 31 35355228
2015 Reduction of RKIP expression promotes nasopharyngeal carcinoma invasion and metastasis by activating Stat3 signaling. Oncotarget 31 25915430
2015 The biological complexity of RKIP signaling in human cancers. Experimental & molecular medicine 31 26403261
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
2020 Downregulation of RKIP promotes radioresistance of nasopharyngeal carcinoma by activating NRF2/NQO1 axis via downregulating miR-450b-5p. Cell death & disease 30 32632129
2014 RKIP Regulates Neural Cell Apoptosis Induced by Exposure to Microwave Radiation Partly Through the MEK/ERK/CREB Pathway. Molecular neurobiology 30 25108669
2017 Overexpression of RKIP and its cross-talk with several regulatory gene products in multiple myeloma. Journal of experimental & clinical cancer research : CR 28 28476134
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
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
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
2023 Penicillin-binding protein (PBP) inhibitor development: A 10-year chemical perspective. Experimental biology and medicine (Maywood, N.J.) 24 38030964
1996 Demonstration and characterization of hippocampal cholinergic neurostimulating peptide (HCNP) processing enzyme activity in rat hippocampus. Neurochemical research 24 9139244
2023 Genome-Wide Identification of PEBP Gene Family in Solanum lycopersicum. International journal of molecular sciences 22 37298136
2015 Ibudilast reverses the decrease in the synaptic signaling protein phosphatidylethanolamine-binding protein 1 (PEBP1) produced by chronic methamphetamine intake in rats. Drug and alcohol dependence 22 25962787
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
2008 RKIP and BRAF aberrations in human nasal polyps and the adjacent turbinate mucosae. Cancer letters 22 18329792
2006 Identification and characterization of PEBP as a calpain substrate. Journal of neurochemistry 22 17018026
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
1996 Possible implication of hippocampal cholinergic neurostimulating peptide (HCNP)-related components in Hirano body formation. Neuropathology and applied neurobiology 21 8930956
2024 XJB-5-131 protects chondrocytes from ferroptosis to alleviate osteoarthritis progression via restoring Pebp1 expression. Journal of orthopaedic translation 20 38304614
2024 Semaglutide protects against diabetes-associated cardiac inflammation via Sirt3-dependent RKIP pathway. British journal of pharmacology 20 39710830
2009 Downregulation of PEBP1 in rat brain cortex in hypoxia. Journal of molecular neuroscience : MN 20 19705086
1996 Distribution of hippocampal cholinergic neurostimulating peptide (HCNP) immunoreactivity in the central nervous system of the rat. Brain research 20 8720492
1996 Distribution of hippocampal cholinergic neurostimulating peptide (HCNP)-like immunoreactivity in organs and tissues of young Wistar rats. Histochemistry and cell biology 20 8824905
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 19 37327313
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
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
2023 Cross-Talks between RKIP and YY1 through a Multilevel Bioinformatics Pan-Cancer Analysis. Cancers 18 37894300
2020 cMET promotes metastasis and epithelial-mesenchymal transition in colorectal carcinoma by repressing RKIP. Journal of cellular physiology 18 33151569
1996 Neuronal expression of hippocampal cholinergic neurostimulating peptide (HCNP)-precursor mRNA in rat brain. Journal of neuroscience research 18 8841981
2022 Understanding Mechanisms of RKIP Regulation to Improve the Development of New Diagnostic Tools. Cancers 17 36291854
2023 Cancer resistance via the downregulation of the tumor suppressors RKIP and PTEN expressions: therapeutic implications. Exploration of targeted anti-tumor therapy 16 37205308
2022 Analysis of the PEBP gene family and identification of a novel FLOWERING LOCUS T orthologue in sugarcane. Journal of experimental botany 16 34893811
2021 The RhoA dependent anti-metastatic function of RKIP in breast cancer. Scientific reports 16 34465801
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
2021 A Functional Network Model of the Metastasis Suppressor PEBP1/RKIP and Its Regulators in Breast Cancer Cells. Cancers 15 34885208
2001 Age-dependent changes in HCNP-related antigen expression in the human hippocampus. Brain research. Developmental brain research 15 11287059
2023 Membrane regulation of 15LOX-1/PEBP1 complex prompts the generation of ferroptotic signals, oxygenated PEs. Free radical biology & medicine 14 37678654
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 14 37977422
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
2021 Insights of RKIP-Derived Suppression of Prostate Cancer. Cancers 13 34945007
2020 Resveratrol binds and activates RKIP protein in colorectal cancer. Amino acids 13 32918615