Affinage

CPE

Carboxypeptidase E · UniProt P16870

Length
476 aa
Mass
53.2 kDa
Annotated
2026-04-28
100 papers in source corpus 16 papers cited in narrative 15 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

Carboxypeptidase E (CPE) is a carboxypeptidase B-like exopeptidase and regulated secretory pathway sorting receptor essential for the biosynthesis of the majority of neuropeptides and peptide hormones. As an exopeptidase, CPE removes C-terminal basic residues (Lys/Arg) from prohormone processing intermediates to generate mature bioactive peptides including alpha-MSH, beta-endorphin, enkephalins, substance P, and insulin; loss of CPE activity causes accumulation of unprocessed intermediates across the brain and pancreatic islets, with carboxypeptidase D providing only partial compensation (PMID:11481435, PMID:19014391, PMID:37967211, PMID:9700764). As a membrane-associated sorting receptor at the trans-Golgi network, CPE binds prohormones such as POMC and directs them into regulated secretory granules; in Cpe-null mice POMC is missorted to the constitutive pathway (PMID:9019408, PMID:12488357). CPE also functions as a secreted signaling molecule that activates mTORC1/RPS6 to suppress glioma cell migration (PMID:28978054) and inhibits Wnt3a secretion and activity through N-terminal-mediated aggregation (PMID:27375026); in the hypothalamus, CPE acts downstream of the FoxO1-POMC axis to promote alpha-MSH production and regulate energy balance (PMID:19767734, PMID:25549049). Homozygous loss-of-function mutation in human CPE causes morbid obesity, type 2 diabetes, intellectual disability, and hypogonadotrophic hypogonadism (PMID:26120850).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 1990 Medium

    Establishing where CPE acts: immunocytochemistry revealed CPE protein concentrated in hypothalamic nuclei, pituitary, hippocampus, and amygdala—matching neuropeptide-rich regions and implying CPE functions in neuropeptide-producing neurons.

    Evidence Immunocytochemistry with specific antisera on rat CNS sections

    PMID:2332799

    Open questions at the time
    • Single method (immunocytochemistry) without functional readout
    • Subcellular compartment identity not resolved at EM level in this study
  2. 1997 High

    CPE was shown to have a dual function—both enzymatic and non-enzymatic—when it was identified as a trans-Golgi network sorting receptor that binds prohormones and directs them into regulated secretory granules; in Cpe(fat) mutant mice, POMC was missorted to the constitutive pathway. Simultaneously, the Ser202Pro mutation was shown to render CPE catalytically inactive and unstable, causing proinsulin processing defects in beta-cells without abolishing regulated secretion per se.

    Evidence Biochemical fractionation and binding assays on pituitary Golgi membranes; Cpe(fat) mouse model; beta-cell lines with EM, Western blot, pulse-chase secretion assays

    PMID:9019408 PMID:9348219

    Open questions at the time
    • Structural basis for prohormone recognition by CPE not determined
    • Whether sorting and enzymatic functions are separable at the domain level remained unclear
  3. 1998 Medium

    CPE's enzymatic role was extended to specific neuropeptides when Cpe(fat) mice were shown to have fivefold reduced amidated substance P across all brain regions, confirming CPE as the rate-limiting C-terminal exopeptidase in protachykinin processing.

    Evidence Radioimmunoassay for amidated and total SP forms in Cpe(fat/fat) vs. control mouse brain

    PMID:9700764

    Open questions at the time
    • Whether other carboxypeptidases partially compensate for SP processing was not assessed
  4. 2001 High

    The scope of CPE's enzymatic activity was revealed to be genome-wide: mass spectrometry of Cpe(fat) mouse brains identified >100 secretory peptides drastically reduced, with accumulation of C-terminal basic-residue intermediates, establishing CPE as the principal neuropeptide-maturing carboxypeptidase. Loss of CPE also secondarily decreased prohormone convertases PC1 and PC2.

    Evidence Anhydrotrypsin affinity chromatography, mass spectrometry, and RIA in Cpe(fat/fat) brain; Western blot for PC1/PC2

    PMID:11038363 PMID:11481435

    Open questions at the time
    • Degree of compensation by carboxypeptidase D not yet quantified
    • Mechanism of secondary PC1/PC2 decrease unknown
  5. 2003 Medium

    Pulse-chase studies showed that even mutant CPE traffics to secretory granules and is secreted in a regulated manner upon GLP-1 stimulation, supporting the model that CPE serves as a sorting/retention receptor independent of its catalytic activity.

    Evidence Pulse-chase, double-label immunofluorescence, and GLP-1-stimulated secretion assays in NIT3 beta-cells

    PMID:12488357

    Open questions at the time
    • Only examined in mutant CPE context; sorting contribution of wild-type CPE not directly measured by pulse-chase
  6. 2008 High

    Quantitative peptidomics across six brain regions confirmed CPE as the dominant neuropeptide-maturing carboxypeptidase but also demonstrated that carboxypeptidase D partially compensates for CPE loss for a subset of peptides.

    Evidence Tandem mass spectrometry peptidomics comparing Cpe(fat/fat) vs. wild-type across amygdala, hippocampus, hypothalamus, prefrontal cortex, striatum, thalamus

    PMID:19014391

    Open questions at the time
    • Quantitative contribution of CPD vs. CPE not determined on a per-substrate basis
    • Peripheral peptidome not assessed
  7. 2009 High

    CPE was placed in the hypothalamic energy-balance circuit when FoxO1 ablation in POMC neurons was shown to upregulate CPE, increasing alpha-MSH production and reducing food intake; viral overexpression of CPE in the arcuate nucleus phenocopied this effect.

    Evidence Conditional Pomc-Foxo1 KO mice; AAV-CPE overexpression in arcuate nucleus; neuropeptide measurements and food intake/body weight phenotyping

    PMID:19767734

    Open questions at the time
    • Direct transcriptional mechanism linking FoxO1 to CPE promoter not shown
    • Whether CPE's sorting or enzymatic function is more important for energy balance not distinguished
  8. 2014 Medium

    The FoxO1-CPE axis was further elaborated: Sirt1 inhibition in hypothalamus increased CPE expression via acetylated/phosphorylated FoxO1, boosting alpha-MSH, TRH, and T3, thereby increasing energy expenditure.

    Evidence Intracerebroventricular Sirt1 inhibitor in diet-induced obese rats; Western blot and immunoassay

    PMID:24773342 PMID:25549049

    Open questions at the time
    • Pharmacological approach; genetic confirmation of Sirt1-CPE link not performed
    • Direct binding of FoxO1 to CPE regulatory elements not demonstrated
  9. 2015 Medium

    A homozygous truncating CPE mutation in a human patient confirmed CPE's essential role in humans, causing morbid obesity, type 2 diabetes, intellectual disability, and hypogonadotrophic hypogonadism—recapitulating the mouse phenotype.

    Evidence Exome sequencing; RNA analysis confirming nonsense-mediated decay; clinical phenotyping

    PMID:26120850

    Open questions at the time
    • Single case report; additional human families needed for full penetrance assessment
    • Specific peptide processing defects not measured in patient tissues
  10. 2016 Medium

    A non-enzymatic extracellular function of CPE was revealed: CPE inhibits Wnt3a secretion and activity by forming aggregates with Wnt3a through its N-terminal domain, independent of carboxypeptidase activity.

    Evidence Co-secretion experiments, co-immunoprecipitation/aggregation assays, Wnt reporter assays, N-terminal deletion and Wnt3a mutagenesis

    PMID:27375026

    Open questions at the time
    • Physiological context for CPE-Wnt3a interaction unclear
    • Single lab; in vivo relevance not tested
    • Structural basis of N-terminal aggregation unknown
  11. 2017 Medium

    Secreted CPE was found to activate mTORC1/RPS6 signaling and suppress Rac1-dependent glioma cell migration, revealing a signaling function for sCPE distinct from its carboxypeptidase activity.

    Evidence Recombinant sCPE treatment and shRNA knockdown in glioma cell lines; phospho-protein blots; mTOR inhibitor rescue; metabolic flux assays

    PMID:28978054

    Open questions at the time
    • Receptor for sCPE on glioma cells not identified
    • In vivo anti-tumor effect not demonstrated
    • Whether enzymatic activity contributes to signaling function not fully excluded
  12. 2023 High

    Top-down proteomics of beta-cell-specific Cpe knockout islets confirmed CPE as the principal proinsulin carboxypeptidase and identified novel proteoform substrates, while showing CPD can compensate for some substrates in the islet.

    Evidence Top-down proteomics of pancreatic islets from beta-cell-specific Cpe conditional KO mice

    PMID:37967211

    Open questions at the time
    • Full substrate specificity rules (CPE vs. CPD preference) not derived
    • Processing kinetics not measured

Open questions

Synthesis pass · forward-looking unresolved questions
  • The receptor or binding partner that transduces the signaling functions of secreted CPE (activation of mTORC1, inhibition of Wnt) has not been identified, and the structural basis for CPE's dual enzymatic/sorting-receptor activities remains unresolved.
  • No crystal structure of full-length CPE
  • Cell-surface receptor for secreted CPE unknown
  • Relative in vivo contributions of enzymatic vs. sorting vs. signaling functions not dissected with separation-of-function mutants

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 5 GO:0038024 cargo receptor activity 2 GO:0098772 molecular function regulator activity 2
Localization
GO:0005576 extracellular region 3 GO:0031410 cytoplasmic vesicle 3 GO:0005794 Golgi apparatus 1 GO:0005886 plasma membrane 1
Pathway
R-HSA-392499 Metabolism of proteins 6 R-HSA-112316 Neuronal System 3 R-HSA-162582 Signal Transduction 2 R-HSA-9609507 Protein localization 2
Partners
CPDFOXO1PCSK1PCSK2POMCWNT3A

Evidence

Reading pass · 15 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1997 Membrane-associated carboxypeptidase E (CPE) functions as a sorting receptor at the trans-Golgi network for regulated secretory pathway proteins, binding prohormones (including pro-opiomelanocortin) to direct them into secretory granules. In Cpe(fat) mutant mice lacking CPE, POMC is missorted to the constitutive secretory pathway and secreted in an unregulated manner. Biochemical fractionation of pituitary Golgi-enriched and secretory granule membranes, binding assays with prohormones, and genetic loss-of-function (Cpe(fat) mice) with secretory pathway readout Cell High 9019408
1990 CPE (carboxypeptidase E/enkephalin convertase) is localized by immunocytochemistry to neuronal cell bodies and terminals throughout the rat CNS, with highest concentrations in the hypothalamus (median eminence, supraoptic, paraventricular, suprachiasmatic nuclei), posterior pituitary, intermediate pituitary melanotropes, hippocampal pyramidal cells, and amygdala—distribution matching that of neuropeptides. Immunocytochemistry with specific polyclonal antisera against purified CPE in rat CNS sections The Journal of Neuroscience Medium 2332799
2001 Carboxypeptidase E is required for the biosynthesis of the majority of neuropeptides in mouse brain and pituitary; Cpe(fat/fat) mice lacking CPE activity accumulate peptide processing intermediates with C-terminal basic residues, and levels of over 100 secretory pathway peptides (from proenkephalin, POMC, protachykinins, chromogranins, secretogranin II) are drastically reduced. Anhydrotrypsin affinity chromatography to isolate C-terminal basic residue-containing intermediates from Cpe(fat/fat) mouse brain; mass spectrometry identification; RIA validation Proceedings of the National Academy of Sciences of the United States of America High 11481435
2001 Loss of CPE activity in Cpe(fat) mice leads to secondary decreases in prohormone convertase PC1 and PC2 levels in brain regions and pituitary, resulting in altered processing of neuropeptides including dynorphin A-17, beta-endorphin, and alpha-MSH that are involved in feeding behavior and body weight regulation. Western blot and immunoassay for PC1, PC2, and neuropeptides in Cpe(fat) vs. wild-type mouse brain regions The Journal of biological chemistry Medium 11038363
1997 The Cpe(fat) point mutation (Ser202Pro) in the CPE coding region results in production of pro-CPE that is catalytically inactive and unstable; in beta-cell lines from Cpe(fat/fat) mice (NIT-2, NIT-3), pro-CPE accumulates in an ER-like compartment and proinsulin processing is defective. Granule morphology is altered (enlarged, electron-lucent). CPE activity is not required for sorting proinsulin into the regulated secretory pathway, as secretion remains stimulable. Beta-cell lines from Cpe(fat/fat) mice; Western blot for pro-CPE and mature CPE; electron microscopy; immunocytochemistry; pulse-chase secretion assays with secretagogues Endocrinology High 9348219
2003 Mutant CPE (from Cpe(fat/fat) mice) has a half-life of ~3 h in NIT3 beta-cells; up to 45% escapes proteasomal degradation and traffics to prohormone convertase 2-containing secretory granules, where it is secreted in a regulated manner upon glucagon-like peptide-1 stimulation, supporting a role for CPE as a sorting/retention receptor in granule trafficking. Pulse-chase experiments in NIT3 cells; double-label immunofluorescence microscopy; secretion assay with GLP-1 stimulation Endocrinology Medium 12488357
2009 FoxO1 ablation in POMC neurons increases CPE expression in the hypothalamus, leading to selective increases of alpha-MSH and carboxy-cleaved beta-endorphin (CPE-dependent POMC processing products), resulting in decreased food intake. Moderate CPE overexpression in the arcuate nucleus phenocopies FoxO1 deletion effects on food intake, placing CPE downstream of FoxO1 in the hypothalamic energy-balance circuit. Conditional Pomc-Foxo1 knockout mice; CPE overexpression in arcuate nucleus via viral vector; measurement of alpha-MSH and beta-endorphin forms; food intake and body weight measurements Nature medicine High 19767734
2016 CPE inhibits the secretion and activity of Wnt3a ligand. CPE and Wnt3a are co-secreted from cells; CPE forms aggregates with Wnt3a through its N-terminal sequence, inducing possible ER stress and causing loss of Wnt3a function, thereby negatively regulating the canonical Wnt signaling pathway. The C-terminal Lys residue of Wnt3a is critical for its activity, but CPE does not act by removing this residue. Co-secretion experiments, co-immunoprecipitation/aggregation assays, Wnt pathway reporter assays, CPE N-terminal deletion and Wnt3a C-terminal mutagenesis Oncogene Medium 27375026
2017 Secreted CPE (sCPE) activates mTORC1 signaling in glioma cells (detected by phosphorylation of RPS6) and reduces glioma cell migration via negative regulation of Rac1 signaling downstream of RPS6. CPE knockdown decreases active RPS6 and increases GBM cell motility. sCPE also shifts glucose metabolism away from aerobic glycolysis toward the TCA cycle. Recombinant sCPE treatment of glioma cell lines; CPE shRNA knockdown; phospho-protein Western blot (RPS6, Rac1); mTOR inhibitor experiments; glucose flux metabolic assays Oncotarget Medium 28978054
1998 CPE is required for normal proteolytic processing of protachykinin to mature amidated substance P (SP) in the brain. Cpe(fat/fat) mice have more than fivefold lower levels of fully processed amidated SP in all brain regions tested compared to controls, while total SP species are unchanged, consistent with CPE acting as the final C-terminal basic residue-removing exopeptidase in SP biosynthesis. Radioimmunoassay for amidated SP and total SP forms in multiple brain regions of Cpe(fat/fat) vs. wild-type and heterozygous mice Peptides Medium 9700764
2008 Quantitative peptidomics in six brain regions of Cpe(fat/fat) mice reveals that CPE contributes to production of the majority of neuropeptides; most secretory pathway peptides are greatly reduced in CPE-null mice, while processing intermediates with C-terminal Lys/Arg are elevated. Some peptides are only partially reduced, indicating that carboxypeptidase D can partially compensate. Tandem mass spectrometry peptidomics with quantitative comparison of Cpe(fat/fat) vs. wild-type mouse brain regions (amygdala, hippocampus, hypothalamus, prefrontal cortex, striatum, thalamus) Journal of neurochemistry High 19014391
2023 Top-down proteomics of beta-cell-specific Cpe knockout mouse islets demonstrates that CPE processes proinsulin by removing C-terminal basic residues and identifies novel proteoforms as CPE substrates; some known substrates remain at near-normal levels, showing that carboxypeptidase D (CPD) can compensate for CPE loss in the pancreatic islet. Top-down proteomics of pancreatic islets from beta-cell-specific Cpe conditional knockout mice; quantitative proteoform analysis Endocrinology High 37967211
2015 A homozygous truncating mutation in human CPE (c.76_98del; p.E26RfsX68) causing loss of CPE expression (nonsense-mediated decay) results in morbid obesity, intellectual disability, type 2 diabetes, and hypogonadotrophic hypogonadism in a human patient, recapitulating the Cpe(fat/fat) and Cpe knockout mouse phenotypes and confirming CPE's role as a peptide/hormone-processing enzyme essential for body weight, metabolism, and reproductive/brain function in humans. Exome sequencing; RNA expression analysis from whole blood; phenotypic characterization PloS one Medium 26120850
2022 CPE protein and mRNA are present within exosomes secreted from cancer cells; exosomal CPE from high-metastatic HCC cells promotes proliferation and invasion of low-metastatic HCC cells. CPE-shRNA-loaded exosomes suppress CPE expression in high-metastatic HCC cells and reduce proliferation via suppression of Cyclin D1 and c-MYC. Exosome isolation from cancer cell supernatants and patient sera; Western blot and PCR for CPE; cell proliferation (MTT, colony formation) and invasion (Matrigel) assays; shRNA knockdown via exosome delivery International journal of molecular sciences Medium 35328535
2014 Central inhibition of Sirt1 in diet-induced obese rats increases CPE expression in the hypothalamus via an acetylated/phosphorylated FoxO1-mediated increase in POMC, leading to greater production of alpha-MSH, elevated TRH and thyroid hormone (T3), and increased energy expenditure, placing CPE as a downstream effector of the Sirt1-FoxO1-POMC axis. Intracerebroventricular Sirt1 inhibitor injection in DIO rats; Western blot and immunoassay for CPE, alpha-MSH, FoxO1 modifications, and thyroid hormones Endocrinology Medium 24773342 25549049

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1997 Carboxypeptidase E is a regulated secretory pathway sorting receptor: genetic obliteration leads to endocrine disorders in Cpe(fat) mice. Cell 385 9019408
2008 A combinatorial code for CPE-mediated translational control. Cell 320 18267074
2000 Phosphorylation of CPE binding factor by Eg2 regulates translation of c-mos mRNA. Nature 300 10749216
1999 Inactivation of the gene (cpe) encoding Clostridium perfringens enterotoxin eliminates the ability of two cpe-positive C. perfringens type A human gastrointestinal disease isolates to affect rabbit ileal loops. Molecular microbiology 181 10476029
2020 Evaluation of SARS-CoV-2 neutralizing antibodies using a CPE-based colorimetric live virus micro-neutralization assay in human serum samples. Journal of medical virology 139 32383254
2009 The obesity susceptibility gene Cpe links FoxO1 signaling in hypothalamic pro-opiomelanocortin neurons with regulation of food intake. Nature medicine 133 19767734
1991 Maturation-specific polyadenylation: in vitro activation by p34cdc2 and phosphorylation of a 58-kD CPE-binding protein. Genes & development 130 1653174
1995 The enterotoxin gene (cpe) of Clostridium perfringens can be chromosomal or plasmid-borne. Molecular microbiology 128 7783636
1998 Identification and characterization of sporulation-dependent promoters upstream of the enterotoxin gene (cpe) of Clostridium perfringens. Journal of bacteriology 112 9422603
2001 Identification of peptides from brain and pituitary of Cpe(fat)/Cpe(fat) mice. Proceedings of the National Academy of Sciences of the United States of America 111 11481435
2004 Cytoplasmic polyadenylation element (CPE)- and CPE-binding protein (CPEB)-independent mechanisms regulate early class maternal mRNA translational activation in Xenopus oocytes. The Journal of biological chemistry 87 14752101
2009 Sporulation and enterotoxin (CPE) synthesis are controlled by the sporulation-specific sigma factors SigE and SigK in Clostridium perfringens. Journal of bacteriology 86 19201796
2008 Spindle-localized CPE-mediated translation controls meiotic chromosome segregation. Nature cell biology 78 18536713
2004 The CcpA protein is necessary for efficient sporulation and enterotoxin gene (cpe) regulation in Clostridium perfringens. Journal of bacteriology 77 15292123
1996 Regulated expression of Clostridium perfringens enterotoxin in naturally cpe-negative type A, B, and C isolates of C. perfringens. Infection and immunity 76 8757868
2008 Peptidomics of Cpe(fat/fat) mouse brain regions: implications for neuropeptide processing. Journal of neurochemistry 75 19014391
2015 Truncating Homozygous Mutation of Carboxypeptidase E (CPE) in a Morbidly Obese Female with Type 2 Diabetes Mellitus, Intellectual Disability and Hypogonadotrophic Hypogonadism. PloS one 64 26120850
2000 Detection of porcine enteroviruses by nRT-PCR: differentiation of CPE groups I-III with specific primer sets. Journal of virological methods 64 10960708
2005 Relative quantitation of peptides in wild-type and Cpe(fat/fat) mouse pituitary using stable isotopic tags and mass spectrometry. Journal of mass spectrometry : JMS 63 15706630
2007 Overexpression of claudin-3 and claudin-4 receptors in uterine serous papillary carcinoma: novel targets for a type-specific therapy using Clostridium perfringens enterotoxin (CPE). Cancer 60 17326053
1997 Beta-cell lines derived from transgenic Cpe(fat)/Cpe(fat) mice are defective in carboxypeptidase E and proinsulin processing. Endocrinology 57 9348219
1994 Expression from the Clostridium perfringens cpe promoter in C. perfringens and Bacillus subtilis. Infection and immunity 57 7960138
2004 Peptidomics of Cpe fat/fat mouse hypothalamus: effect of food deprivation and exercise on peptide levels. The Journal of biological chemistry 55 15572367
2011 Use of Clostridium perfringens Enterotoxin and the Enterotoxin Receptor-Binding Domain (C-CPE) for Cancer Treatment: Opportunities and Challenges. Journal of toxicology 54 21941545
2001 Impaired prohormone convertases in Cpe(fat)/Cpe(fat) mice. The Journal of biological chemistry 52 11038363
2009 Recombinant CPE fused to tumor necrosis factor targets human ovarian cancer cells expressing the claudin-3 and claudin-4 receptors. Molecular cancer therapeutics 51 19567823
2007 Clostridium perfringens type A strains carrying a plasmid-borne enterotoxin gene (genotype IS1151-cpe or IS1470-like-cpe) as a common cause of food poisoning. Journal of clinical microbiology 51 18003798
2013 Claudins overexpression in ovarian cancer: potential targets for Clostridium Perfringens Enterotoxin (CPE) based diagnosis and therapy. International journal of molecular sciences 50 23685873
2013 Evaluation of a new real-time PCR assay (Check-Direct CPE) for rapid detection of KPC, OXA-48, VIM, and NDM carbapenemases using spiked rectal swabs. Diagnostic microbiology and infectious disease 49 24135412
2004 Multiplex PCR genotyping assay that distinguishes between isolates of Clostridium perfringens type A carrying a chromosomal enterotoxin gene (cpe) locus, a plasmid cpe locus with an IS1470-like sequence, or a plasmid cpe locus with an IS1151 sequence. Journal of clinical microbiology 49 15071003
2002 Organization of the plasmid cpe Locus in Clostridium perfringens type A isolates. Infection and immunity 47 12117935
2015 Clinical Performance of Check-Direct CPE, a Multiplex PCR for Direct Detection of bla(KPC), bla(NDM) and/or bla(VIM), and bla(OXA)-48 from Perirectal Swabs. Journal of clinical microbiology 43 26338860
2008 Noncytotoxic Clostridium perfringens enterotoxin (CPE) variants localize CPE intestinal binding and demonstrate a relationship between CPE-induced cytotoxicity and enterotoxicity. Infection and immunity 43 18505809
2012 A wide variety of Clostridium perfringens type A food-borne isolates that carry a chromosomal cpe gene belong to one multilocus sequence typing cluster. Applied and environmental microbiology 41 22865060
2015 Multicentre evaluation of the Check-Direct CPE® assay for direct screening of carbapenemase-producing Enterobacteriaceae from rectal swabs. The Journal of antimicrobial chemotherapy 38 25637518
1998 Genes for the CPE receptor (CPETR1) and the human homolog of RVP1 (CPETR2) are localized within the Williams-Beuren syndrome deletion. Genomics 37 9878248
2012 A novel method for high-throughput screening to quantify antiviral activity against viruses that induce limited CPE. Journal of virological methods 35 22575574
2006 Altered neuropeptide processing in prefrontal cortex of Cpe (fat/fat) mice: implications for neuropeptide discovery. Journal of neurochemistry 35 16417576
2018 Acetic acid as a decontamination method for ICU sink drains colonized by carbapenemase-producing Enterobacteriaceae and its effect on CPE infections. The Journal of hospital infection 34 30579969
2018 Oral Administration of Recombinant Saccharomyces boulardii Expressing Ovalbumin-CPE Fusion Protein Induces Antibody Response in Mice. Frontiers in microbiology 32 29706942
2012 Claudin-6: a novel receptor for CPE-mediated cytotoxicity in ovarian cancer. Oncogenesis 31 23552466
1990 Carboxypeptidase E (CPE): immunocytochemical localization in the rat central nervous system and pituitary gland. The Journal of neuroscience : the official journal of the Society for Neuroscience 31 2332799
2013 Emergence of anxiety-like behaviours in depressive-like Cpe(fat/fat) mice. The international journal of neuropsychopharmacology 29 23442571
2010 The relevance of protein-protein interactions for p53 function: the CPE contribution. Protein engineering, design & selection : PEDS 29 20952436
2022 Case report: Dramatic response to alectinib in a lung adenosquamous carcinoma patient harbouring a novel CPE-ALK fusion. Frontiers in oncology 27 37082099
2010 Organization of the cpe locus in CPE-positive clostridium perfringens type C and D isolates. PloS one 27 20532170
2003 Development of a duplex PCR genotyping assay for distinguishing Clostridium perfringens type A isolates carrying chromosomal enterotoxin (cpe) genes from those carrying plasmid-borne enterotoxin (cpe) genes. Journal of clinical microbiology 26 12682135
2014 Central Sirt1 regulates body weight and energy expenditure along with the POMC-derived peptide α-MSH and the processing enzyme CPE production in diet-induced obese male rats. Endocrinology 25 25549049
2006 Electrochemical detection of short sequences related to the hepatitis B virus using MB on chitosan-modified CPE. Bioelectrochemistry (Amsterdam, Netherlands) 24 17084111
2003 Trafficking of mutant carboxypeptidase E to secretory granules in a beta-cell line derived from Cpe(fat)/Cpe(fat) mice. Endocrinology 23 12488357
1997 Interleukin-8 selectively enhances cytopathic effect (CPE) induced by positive-strand RNA viruses in the human WISH cell line. Biochemical and biophysical research communications 23 9207237
2019 Phylogenomic analysis of gastroenteritis-associated Clostridium perfringens in England and Wales over a 7-year period indicates distribution of clonal toxigenic strains in multiple outbreaks and extensive involvement of enterotoxin-encoding (CPE) plasmids. Microbial genomics 22 31553300
2015 Synthesis of histone proteins by CPE ligation using a recombinant peptide as the C-terminal building block. Journal of biochemistry 21 26002961
1999 Evidence for Clostridium perfringens enterotoxin (CPE) inducing a mitogenic and cytokine response in vitro and a cytokine response in vivo. Current microbiology 21 9871107
2022 Exosomal Carboxypeptidase E (CPE) and CPE-shRNA-Loaded Exosomes Regulate Metastatic Phenotype of Tumor Cells. International journal of molecular sciences 20 35328535
2021 Effective Oncoleaking Treatment of Pancreatic Cancer by Claudin-Targeted Suicide Gene Therapy with Clostridium perfringens Enterotoxin (CPE). Cancers 20 34503203
2015 Claudin-binder C-CPE mutants enhance permeability of insulin across human nasal epithelial cells. Drug delivery 20 26036653
1996 Clostridium perfringens type A enterotoxin (CPE): more than just explosive diarrhea. Critical reviews in microbiology 20 8989513
2013 Upregulation of CPE promotes cell proliferation and tumorigenicity in colorectal cancer. BMC cancer 19 24006921
2008 Spread of a large plasmid carrying the cpe gene and the tcp locus amongst Clostridium perfringens isolates from nosocomial outbreaks and sporadic cases of gastroenteritis in a geriatric hospital. Epidemiology and infection 19 18485266
2020 Microporous Metal-Organic Framework (MOF)-Based Composite Polymer Electrolyte (CPE) Mitigating Lithium Dendrite Formation in All-Solid-State-Lithium Batteries. ACS omega 17 32309697
2015 A genosensor based on CPE for study the interaction between ketamine as an anesthesia drug with DNA. International journal of biological macromolecules 16 26188294
2014 Downregulation of CPE regulates cell proliferation and chemosensitivity in pancreatic cancer. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 16 25374060
2012 Strong ion exchange in centrifugal partition extraction (SIX-CPE): effect of partition cell design and dimensions on purification process efficiency. Journal of chromatography. A 16 22677413
2009 PC2/CPE-mediated pro-protein processing in tumor cells and its differentiated cells or tissues. Molecular and cellular endocrinology 16 19428990
2004 Enumeration and isolation of cpe-positive Clostridium perfringens spores from feces. Journal of clinical microbiology 16 15364981
2020 Simultaneous Determination of Six Isoflavones from Puerariae Lobatae Radix by CPE-HPLC and Effect of Puerarin on Tyrosinase Activity. Molecules (Basel, Switzerland) 15 31952126
2020 Differentiation of Cytopathic Effects (CPE) induced by influenza virus infection using deep Convolutional Neural Networks (CNN). PLoS computational biology 15 32401790
2019 The prevalence of plasmid-coded cpe enterotoxin, β2 toxin, tpeL toxin, and tetracycline resistance in Clostridium perfringens strains isolated from different sources. Anaerobe 15 30802555
2012 Comparative genomic hybridization analysis shows different epidemiology of chromosomal and plasmid-borne cpe-carrying Clostridium perfringens type A. PloS one 15 23094024
2005 Genetic modifiers interact with Cpe(fat) to affect body weight, adiposity, and hyperglycemia. Physiological genomics 15 15870393
2021 Longitudinal Genomic Characterization of Carbapenemase-producing Enterobacteriaceae (CPE) Reveals Changing Pattern of CPE Isolated in Hong Kong Hospitals. International journal of antimicrobial agents 14 34525401
2015 In vitro cytotoxicity induced by Clostridium perfringens isolate carrying a chromosomal cpe gene is exclusively dependent on sporulation and enterotoxin production. Microbial pathogenesis 14 25912832
2012 Evaluation of progressive multifocal leukoencephalopathy treatments in a Spanish cohort of HIV-infected patients: do protease inhibitors improve survival regardless of central nervous system penetration-effectiveness (CPE) score? HIV medicine 14 23217049
2002 Developmental changes in opioid peptides and their receptors in Cpe(fat)/Cpe(fat) mice lacking peptide processing enzyme carboxypeptidase E. The Journal of pharmacology and experimental therapeutics 13 12438557
2017 The pleiotropic vegetative and sexual development phenotypes of Neurospora crassa arise from double mutants of the calcium signaling genes plc-1, splA2, and cpe-1. Current genetics 12 28265741
2017 Effects of soluble CPE on glioma cell migration are associated with mTOR activation and enhanced glucose flux. Oncotarget 12 28978054
2015 Claudin-4 binder C-CPE 194 enhances effects of anticancer agents on pancreatic cancer cell lines via a MAPK pathway. Pharmacology research & perspectives 12 27022469
2014 Folding and stability studies on C-PE and its natural N-terminal truncant. Archives of biochemistry and biophysics 12 24434005
2014 Central Sirt1 regulates body weight and energy expenditure along with the POMC-derived peptide α-MSH and the processing enzyme CPE production in diet-induced obese male rats. Endocrinology 12 24773342
1993 Mechanism of resistance to cyclopentenyl cytosine (CPE-C) in Molt-4 lymphoblasts. Biochemical pharmacology 12 8471071
1986 Dominance of the CPE(+) phenotype in hybrid Aedes albopictus cells infected with Sindbis virus. Virus research 12 3765819
2018 Identification of CPE and GAIT elements in 3'UTR of macrophage migration inhibitory factor (MIF) involved in inflammatory response induced by LPS in Ciona robusta. Molecular immunology 11 29702356
2004 PCR identification of the plasmid-borne enterotoxin gene (cpe) in Clostridium perfringens strains isolated from food poisoning outbreaks. International journal of medical microbiology : IJMM 11 15532984
2003 Study of interactions between actinomycin D and DNA on carbon paste electrode (CPE) and on the hanging mercury drop (HMDE) surface. Journal of pharmaceutical and biomedical analysis 11 12667923
1999 Altered biosynthesis and secretion of pro-opiomelanocortin in the intermediate and anterior pituitary of carboxypeptidase E-deficient, Cpe(fat)/ Cpe(fat)mice. Neuropeptides 10 10657504
2022 Prevalence of cpe-positive Clostridium perfringens in surface-attached soil of commercially available potatoes and its significance as a potential source of food poisoning. Anaerobe 9 36549463
2009 Neutralizing antibodies against IFN beta in patients with multiple sclerosis: a comparative study of two cytopathic effect tests (CPE) for their detection. Journal of immunological methods 9 19786034
1991 Identification of a common Plasmodium epitope (CPE) recognised by a pan-specific inhibitory monoclonal antibody. Molecular and biochemical parasitology 9 1723149
2022 CHIKV strains Brazil (wt) and Ross (lab-adapted) differ with regard to cell host range and antiviral sensitivity and show CPE in human glioblastoma cell lines U138 and U251. Virus genes 8 35347588
2016 Carboxypeptidase E (CPE) inhibits the secretion and activity of Wnt3a. Oncogene 8 27375026
2014 Differential outgrowth potential of Clostridium perfringens food-borne isolates with various cpe-genotypes in vacuum-packed ground beef during storage at 12°C. International journal of food microbiology 8 25461607
2023 Top-Down Proteomics of Mouse Islets With Beta Cell CPE Deletion Reveals Molecular Details in Prohormone Processing. Endocrinology 7 37967211
2016 An optimized work-flow to reduce time-to-detection of carbapenemase-producing Enterobacteriaceae (CPE) using direct testing from rectal swabs. Bioengineered 6 27533488
1998 Reduced levels of substance P in the brains of Cpe(fat)/Cpe(fat) mice. Peptides 6 9700764
1992 Evaluation of the shell vial pre-CPE method using monoclonal antibodies for the diagnosis of human cytomegalovirus infection in the field of pediatrics. In vivo (Athens, Greece) 6 1333832
2022 CPE Regulates Proliferation and Apoptosis of Primary Myocardial Cells Mediated by Ischemia and Hypoxia Injury. Journal of healthcare engineering 5 35340224
2021 In silico analysis of non-synonymous missense SNPs (nsSNPs) in CPE, GNAS genes and experimental validation in type II diabetes mellitus through Next Generation Sequencing. Genomics 5 34029697
2016 SiO2 nanoparticles modified CPE as a biosensor for determination of i-motif DNA/Tamoxifen interaction. International journal of biological macromolecules 5 27151665
2015 Oncoleaking: Use of the Pore-Forming Clostridium perfringens Enterotoxin (CPE) for Suicide Gene Therapy. Methods in molecular biology (Clifton, N.J.) 5 26072402