Affinage

CPE

Carboxypeptidase E · UniProt P16870

Length
476 aa
Mass
53.2 kDa
Annotated
2026-06-09
100 papers in source corpus 19 papers cited in narrative 18 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

Carboxypeptidase E (CPE) is a carboxypeptidase B-like exopeptidase concentrated in neuronal cell bodies and terminals throughout the CNS and pituitary, with highest expression in hypothalamic and pituitary neuroendocrine centers, where it serves as the terminal enzyme in neuropeptide and peptide hormone biosynthesis (PMID:2332799). It removes C-terminal basic residues from prohormone processing intermediates: peptidomic and proteomic analyses of Cpe(fat) and beta-cell-specific knockout models show that loss of CPE causes accumulation of >100 C-terminally basic intermediates from at least 16 secretory pathway precursors—including POMC, proenkephalin, prodynorphin, protachykinin, and proinsulin—with reduced levels of the corresponding mature peptides (PMID:11481435, PMID:19014391, PMID:37967211, PMID:9700764, PMID:12438557). Carboxypeptidase D partially compensates for CPE loss for a subset of substrates (PMID:19014391, PMID:37967211), and CPE loss also lowers PC1/PC2 convertase levels, indirectly impairing upstream endoproteolytic processing (PMID:11038363). Independently of its enzymatic activity, CPE acts as a sorting receptor at the trans-Golgi network, binding prohormones to direct them into the regulated secretory pathway; in CPE-deficient pituitary cells POMC is missorted to the constitutive pathway (PMID:9019408). In the hypothalamus CPE functions downstream of Sirt1/FoxO1 signaling to control POMC-derived alpha-MSH and beta-endorphin production, energy balance, and the hypothalamic-pituitary-thyroid axis (PMID:19767734, PMID:25549049, PMID:24773342). A human homozygous truncating CPE mutation causes morbid obesity, intellectual disability, abnormal glucose homeostasis, and hypogonadotrophic hypogonadism, establishing CPE as essential for hormone processing governing body weight, metabolism, and reproduction (PMID:26120850). Several non-canonical roles have also been documented: CPE inhibits Wnt3a by forming aggregates via its N-terminal domain without enzymatic cleavage (PMID:27375026), secreted CPE activates mTORC1/RPS6 signaling to suppress glioma migration and aerobic glycolysis (PMID:28978054), and CPE modulates cancer cell proliferation through cyclin D1/p21/p27 and NF-κB pathways (PMID:24006921, PMID:25374060).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 1990 Medium

    Established where CPE acts by mapping its anatomical distribution, linking the enzyme to neuropeptide-producing neuroendocrine centers.

    Evidence Immunocytochemistry with specific antisera across rat brain and pituitary

    PMID:2332799

    Open questions at the time
    • Localization is anatomical, not subcellular at processing sites
    • Does not demonstrate enzymatic function on specific substrates
  2. 1997 High

    Resolved whether CPE has a function beyond enzymatic trimming, showing it acts as a TGN sorting receptor that routes prohormones to the regulated secretory pathway.

    Evidence Prohormone binding assays in Golgi/granule membranes plus missorting analysis in Cpe(fat) mice

    PMID:9019408

    Open questions at the time
    • Structural basis of prohormone recognition not defined
    • Sorting role not universal across substrates (proinsulin sorting independent of CPE)
  3. 1997 High

    Separated CPE's enzymatic processing role from sorting in beta-cells, showing CPE is needed for proinsulin processing but not for regulated sorting of insulin.

    Evidence Pulse-chase, EM, ICC, and secretion assays in Cpe(fat)-derived beta-cell lines

    PMID:9348219

    Open questions at the time
    • Mechanism of pro-CPE ER retention in mutant cells not fully resolved
    • Does not address sorting role in other cell types
  4. 1999 Medium

    Demonstrated CPE's substrate-specific requirement for a defined neuropeptide, establishing it as the C-terminal basic residue-removing enzyme for substance P.

    Evidence RIA distinguishing amidated mature vs. total SP in Cpe(fat/fat) brain regions

    PMID:9700764

    Open questions at the time
    • Single substrate; relies on indirect RIA discrimination
    • No direct in vitro cleavage demonstration
  5. 2001 High

    Defined the breadth of CPE's role by showing it is the terminal exopeptidase for the majority of neuroendocrine peptides, and that its loss secondarily reduces convertase levels.

    Evidence Affinity-capture peptidomics with MS and RIA; Western/IHC/RIA for convertases and opioid peptides in Cpe(fat) mice

    PMID:11038363 PMID:11481435

    Open questions at the time
    • Convertase reduction is correlative, mechanism of indirect effect unclear
    • Does not distinguish enzymatic vs. sorting contributions to each peptide deficit
  6. 2002 Medium

    Extended CPE's processing role to opioid peptides during development and linked peptide deficits to altered receptor signaling.

    Evidence Developmental RIA and [35S]GTPgammaS receptor functional assays across brain regions in Cpe(fat/fat) mice

    PMID:12438557

    Open questions at the time
    • Receptor activity changes are downstream/correlative
    • Region- and peptide-specific effects not mechanistically explained
  7. 2003 Medium

    Characterized the fate of mutant pro-CPE, showing partial escape from degradation and trafficking to secretory granules, supporting a retention/sorting role even for the mutant form.

    Evidence Pulse-chase, co-localization with calnexin/PC2, and stimulated secretion in NIT3 cells

    PMID:12488357

    Open questions at the time
    • Functional consequence of mutant trafficking unclear
    • Single cell-line system
  8. 2008 High

    Quantitatively confirmed CPE's global contribution to neuropeptide biosynthesis and revealed partial CPD compensation across brain regions.

    Evidence Quantitative tandem-MS peptidomics across six brain regions of Cpe(fat/fat) mice

    PMID:19014391

    Open questions at the time
    • Compensation mechanism by CPD not defined
    • Does not resolve which deficits are sorting- vs. enzyme-dependent
  9. 2009 High

    Placed CPE in a hypothalamic regulatory circuit, showing it acts downstream of FoxO1 to control POMC-derived peptide production and energy balance.

    Evidence POMC-specific FoxO1 knockout plus arcuate CPE overexpression with feeding/weight phenotyping

    PMID:19767734

    Open questions at the time
    • Direct transcriptional link between FoxO1 and CPE not fully mapped
    • Other FoxO1 targets may contribute
  10. 2013 Medium

    Implicated CPE in cancer cell proliferation, showing it drives cell-cycle progression via cyclin D1/p21/p27 in colorectal cancer.

    Evidence CPE overexpression/depletion with proliferation, cell-cycle, soft-agar assays and qRT-PCR readouts

    PMID:24006921

    Open questions at the time
    • No rescue experiments
    • Molecular link from CPE to cell-cycle regulators undefined
  11. 2014 Medium

    Connected CPE to oncogenic NF-κB signaling in pancreatic cancer through knockdown and pharmacological epistasis.

    Evidence siRNA knockdown, proliferation/invasion assays, xenograft, and NF-κB inhibitor epistasis

    PMID:25374060

    Open questions at the time
    • Direct molecular mechanism linking CPE to NF-κB unknown
    • Single cancer context
  12. 2014 Medium

    Extended the FoxO1 circuit upstream, showing central Sirt1 controls CPE expression to regulate POMC processing and the HPT axis.

    Evidence ICV Sirt1 inhibition with FoxO1 acetylation/phosphorylation, alpha-MSH RIA, and TRH/T3 measures in DIO rats

    PMID:24773342 PMID:25549049

    Open questions at the time
    • Indirect pharmacological perturbation
    • Direct Sirt1-FoxO1-CPE molecular linkage inferred not shown
  13. 2015 Medium

    Established human disease relevance, showing a truncating CPE mutation causes obesity, intellectual disability, glucose dysregulation, and hypogonadism.

    Evidence Exome sequencing, NMD confirmation, and clinical phenotyping of a homozygous patient

    PMID:26120850

    Open questions at the time
    • Single patient
    • Cannot dissect enzymatic vs. sorting contributions to each phenotype
  14. 2016 Medium

    Identified a non-enzymatic CPE function, showing it inhibits Wnt3a by N-terminal-mediated aggregation rather than cleavage.

    Evidence Co-secretion, Wnt3a C-terminal Lys mutagenesis, co-IP/aggregation, and Wnt reporter assays

    PMID:27375026

    Open questions at the time
    • Physiological relevance of Wnt inhibition not established in vivo
    • Single lab biochemical system
  15. 2017 Medium

    Defined a secreted CPE signaling role, showing extracellular CPE activates mTORC1/RPS6 to suppress glioma migration and aerobic glycolysis.

    Evidence Recombinant sCPE treatment, phospho-RPS6 blots, mTOR/Rac1 pharmacological rescue, knockdown, and metabolic flux analysis

    PMID:28978054

    Open questions at the time
    • Receptor/mechanism by which sCPE triggers mTORC1 unknown
    • Single tumor context
  16. 2022 Medium

    Showed CPE can be transmitted between cancer cells via exosomes to promote proliferation and invasion.

    Evidence Exosome isolation, CPE detection, proliferation/invasion assays, and CPE-shRNA exosome delivery in HCC cells

    PMID:35328535

    Open questions at the time
    • Molecular mechanism of exosomal CPE action unresolved
    • Effects on cyclin D1/c-MYC correlative
  17. 2023 High

    Provided substrate-level resolution of CPE function, directly identifying improperly processed proinsulin proteoforms and confirming CPD compensation.

    Evidence Top-down proteomics of beta-cell-specific Cpe knockout islets

    PMID:37967211

    Open questions at the time
    • Mechanism and regulation of CPD compensation not defined
    • Beta-cell context only

Open questions

Synthesis pass · forward-looking unresolved questions
  • How CPE's enzymatic, TGN-sorting, and extracellular signaling functions are molecularly partitioned, and how secreted/exosomal CPE engages cell-surface signaling, remain unresolved.
  • No structural model linking sorting-receptor and catalytic activities
  • Receptor for secreted CPE in mTORC1 activation unidentified
  • Mechanism of CPD functional compensation undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 5 GO:0016787 hydrolase activity 2 GO:0038024 cargo receptor activity 1
Localization
GO:0005576 extracellular region 3 GO:0031410 cytoplasmic vesicle 2 GO:0005794 Golgi apparatus 1
Pathway
R-HSA-392499 Metabolism of proteins 4 R-HSA-162582 Signal Transduction 3 R-HSA-9609507 Protein localization 1
Partners
WNT3A

Evidence

Reading pass · 18 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: CPE specifically bound prohormones (but not constitutively secreted proteins) in pituitary Golgi-enriched and secretory granule membranes, and in Cpe(fat) mice lacking CPE, pro-opiomelanocortin was missorted to the constitutive pathway and secreted in an unregulated manner. Biochemical binding assays with pituitary Golgi-enriched and secretory granule membrane fractions; in vivo missecretion analysis in Cpe(fat) mutant mice Cell High 9019408
1997 CPE is required for normal proinsulin processing in pancreatic beta-cells: beta-cell lines from Cpe(fat)/Cpe(fat) mice accumulate pro-CPE (not mature CPE) in an ER-like compartment and show defective proinsulin processing, with enlarged electron-lucent granules observed by electron microscopy. Notably, insulin/proinsulin secretion remains regulated (stimulated by secretagogues), indicating CPE is not required for sorting proinsulin to the regulated pathway. Pulse-chase metabolic labeling, immunocytochemistry, electron microscopy, secretion assays in Cpe(fat)/Cpe(fat)-derived NIT-2/NIT-3 beta-cell lines Endocrinology High 9348219
1990 CPE (carboxypeptidase E) is a carboxypeptidase B-like enzyme localized in neuronal cell bodies and terminals throughout the rat CNS and pituitary, with highest concentration in hypothalamic nuclei (median eminence, supraoptic, paraventricular, suprachiasmatic), posterior pituitary, intermediate pituitary melanotropes, and hippocampal pyramidal cells, consistent with a role in neuropeptide biosynthesis. Immunocytochemistry using specific polyclonal antisera to purified CPE enzyme in rat brain sections The Journal of neuroscience Medium 2332799
2001 CPE activity is required for normal biosynthesis of the majority of neuroendocrine peptides: peptidomic analysis of Cpe(fat/fat) mouse brain and pituitary identified over 100 peptides accumulating as C-terminally basic processing intermediates from 16 secretory pathway proteins including proenkephalin, POMC, protachykinins, and chromogranins, demonstrating CPE's broad substrate scope as the terminal exopeptidase. Affinity chromatography on anhydrotrypsin resin followed by mass spectrometry peptide identification; radioimmunoassay validation in wild-type mice 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 reduced levels of PC1 and PC2 prohormone convertases in brain and pituitary, resulting in decreased alpha-MSH, altered beta-endorphin processing, and increased dynorphin A-17, indicating CPE activity indirectly supports endoproteolytic processing by maintaining normal convertase levels. Western blot and immunohistochemistry for PC1, PC2 in multiple brain regions; radioimmunoassay for opioid peptides in Cpe(fat) vs. wild-type mice The Journal of biological chemistry Medium 11038363
2003 Mutant CPE (pro-CPE202) from Cpe(fat)/Cpe(fat) mice has a half-life of ~3 h in beta-cells, with up to 45% escaping proteasomal degradation and trafficking to PC2-containing secretory granules (post-Golgi regulated secretory pathway), where it is secreted in a stimulated manner, supporting a potential sorting/retention receptor role even for the mutant form. Pulse-chase experiments, double-label immunofluorescence microscopy with calnexin and PC2 markers, stimulated secretion assay with glucagon-like peptide-1 in NIT3 cells Endocrinology Medium 12488357
2008 Quantitative peptidomics of six brain regions of Cpe(fat/fat) mice demonstrated that CPE contributes to biosynthesis of the majority of neuropeptides; most secretory pathway peptides were greatly reduced while C-terminally basic processing intermediates were elevated, with partial compensation by carboxypeptidase D for a subset of peptides. Quantitative peptidomics with tandem mass spectrometry comparing six brain regions of Cpe(fat/fat) vs. wild-type mice Journal of neurochemistry High 19014391
2009 FoxO1 ablation in POMC neurons increases CPE expression, leading to selective increases in alpha-MSH and carboxy-cleaved beta-endorphin (CPE-dependent POMC processing products), decreased food intake, and protection against diet-induced obesity; moderate CPE overexpression in the arcuate nucleus phenocopied these effects, placing CPE downstream of FoxO1 in hypothalamic energy balance regulation. Conditional FoxO1 knockout in POMC neurons; CPE overexpression via viral vector in arcuate nucleus; neuropeptide measurements; feeding and body weight phenotyping Nature medicine High 19767734
1999 CPE is required for normal processing of substance P from pro-tachykinin: amidated mature SP was more than fivefold lower in all brain regions of Cpe(fat/fat) mice compared to controls, while total SP species (including processing intermediates) were unchanged, demonstrating CPE's specific role as the C-terminal basic residue-removing enzyme in SP biosynthesis. Radioimmunoassay measuring amidated SP vs. total SP forms in multiple brain regions of Cpe(fat/fat) vs. wild-type and heterozygous mice Peptides Medium 9700764
2016 CPE inhibits Wnt3a activity by forming aggregates with Wnt3a via CPE's N-terminal sequence, leading to Wnt3a loss of function; the C-terminal Lys residue of Wnt3a is critical for its activity and important for CPE's effect on the Wnt pathway, but CPE does not act by removing this residue enzymatically. CPE and Wnt3a are co-secreted from cells. Co-secretion assays, mutagenesis of Wnt3a C-terminal Lys, co-immunoprecipitation/aggregation assays, Wnt pathway reporter assays Oncogene Medium 27375026
2017 Secreted CPE (sCPE) activates mTORC1 signaling in glioma cells (detected by RPS6 phosphorylation) and inhibits glioma cell migration via negative regulation of Rac1 signaling through RPS6; mTOR inhibition or Rac1 stimulation reversed the anti-migratory effect of sCPE. sCPE also enhances glucose flux into the TCA cycle at the expense of lactate production, reducing aerobic glycolysis. Recombinant sCPE treatment of glioma cells; phospho-RPS6 Western blot; mTOR inhibitor and Rac1 activator pharmacological rescue; CPE knockdown; metabolic flux analysis Oncotarget Medium 28978054
2022 CPE is present as mRNA and protein in cancer cell-derived exosomes; exosomal CPE from high-metastatic HCC97H cells promotes proliferation and invasion of low-metastatic HCC97L cells, and CPE-shRNA-loaded exosomes suppress CPE expression along with Cyclin D1 and c-MYC in high-metastatic cells, inhibiting their proliferation. Exosome isolation and characterization; Western blot and PCR for CPE in exosomes; MTT, colony formation, and Matrigel invasion assays; CPE-shRNA exosome delivery International journal of molecular sciences Medium 35328535
2013 CPE promotes cell proliferation and tumorigenicity in colorectal cancer cells through downregulation of p21 and p27 and upregulation of cyclin D1, resulting in increased S-phase fraction; overexpression enhanced anchorage-independent growth in soft agar. CPE overexpression and depletion plasmids; MTT, colony formation, BrdU incorporation, flow cytometry, soft agar assays; qRT-PCR for p21, p27, cyclin D1 BMC cancer Medium 24006921
2014 CPE regulates NF-κB activity in pancreatic cancer: siRNA-mediated CPE knockdown inhibited cancer cell growth, migration, and tumor growth in vivo, and directly reduced NF-κB expression; NF-κB inhibition phenocopied CPE knockdown effects, placing NF-κB downstream of CPE. siRNA knockdown of CPE; proliferation and invasion assays; in vivo xenograft; Western blot for NF-κB; NF-κB inhibitor pharmacological epistasis Tumour biology Medium 25374060
2023 Top-down proteomics of beta-cell-specific Cpe knockout mouse islets identified multiple novel proteoforms of improperly processed proinsulin with dibasic C-terminal residues as direct CPE substrates; carboxypeptidase D (CPD) compensates for CPE loss and maintains near-normal processing of some CPE substrates. Top-down proteomics of islets from beta-cell-specific Cpe knockout mice; quantitative comparison of hormone proteoforms Endocrinology High 37967211
2015 A homozygous truncating mutation of CPE (c.76_98del; p.E26RfsX68) in a human patient causes morbid obesity, intellectual disability, abnormal glucose homeostasis, and hypogonadotrophic hypogonadism with no CPE expression detected (consistent with nonsense-mediated decay), establishing that CPE is essential for peptide/hormone processing regulating body weight, metabolism, brain, and reproductive function in humans. Exome sequencing; RNA expression analysis from blood-derived RNA confirming nonsense-mediated decay; phenotypic characterization PloS one Medium 26120850
2014 Central Sirt1 inhibition in diet-induced obese rats increases CPE expression (via FoxO1 acetylation/phosphorylation), leading to increased alpha-MSH production from POMC processing and activation of the hypothalamic-pituitary-thyroid axis, placing CPE downstream of Sirt1/FoxO1 in the POMC processing pathway for energy expenditure regulation. Central Sirt1 inhibition (ICV injection); Western blot for CPE, FoxO1, phospho-FoxO1, acetyl-FoxO1; RIA for alpha-MSH; TRH and T3 measurements in DIO rats Endocrinology Medium 24773342 25549049
2002 CPE is required for normal biosynthesis of opioid peptides from prodynorphin and proenkephalin during development: Cpe(fat/fat) mice accumulate C-terminally extended forms of all three opioid peptides examined, with region-specific decreases in mature dynorphin peptides and differential alterations in Met-enkephalin levels. Loss of CPE also differentially alters mu (but not kappa) opioid receptor functional activity in select brain regions. Peptide extraction and RIA from multiple brain regions at different developmental ages; [35S]GTPgammaS binding assay for mu and kappa receptor functional activity in Cpe(fat/fat) vs. littermate controls The Journal of pharmacology and experimental therapeutics Medium 12438557

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 387 9019408
2008 A combinatorial code for CPE-mediated translational control. Cell 322 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 142 32383254
2009 The obesity susceptibility gene Cpe links FoxO1 signaling in hypothalamic pro-opiomelanocortin neurons with regulation of food intake. Nature medicine 134 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
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 112 11481435
1998 Identification and characterization of sporulation-dependent promoters upstream of the enterotoxin gene (cpe) of Clostridium perfringens. Journal of bacteriology 112 9422603
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 65 26120850
2000 Detection of porcine enteroviruses by nRT-PCR: differentiation of CPE groups I-III with specific primer sets. Journal of virological methods 65 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
2011 Use of Clostridium perfringens Enterotoxin and the Enterotoxin Receptor-Binding Domain (C-CPE) for Cancer Treatment: Opportunities and Challenges. Journal of toxicology 55 21941545
2004 Peptidomics of Cpe fat/fat mouse hypothalamus: effect of food deprivation and exercise on peptide levels. The Journal of biological chemistry 55 15572367
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 44 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 42 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 36 22575574
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 35 30579969
2006 Altered neuropeptide processing in prefrontal cortex of Cpe (fat/fat) mice: implications for neuropeptide discovery. Journal of neurochemistry 35 16417576
2012 Claudin-6: a novel receptor for CPE-mediated cytotoxicity in ovarian cancer. Oncogenesis 33 23552466
2018 Oral Administration of Recombinant Saccharomyces boulardii Expressing Ovalbumin-CPE Fusion Protein Induces Antibody Response in Mice. Frontiers in microbiology 32 29706942
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
2022 Case report: Dramatic response to alectinib in a lung adenosquamous carcinoma patient harbouring a novel CPE-ALK fusion. Frontiers in oncology 29 37082099
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
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
2015 Claudin-binder C-CPE mutants enhance permeability of insulin across human nasal epithelial cells. Drug delivery 21 26036653
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
2013 Upregulation of CPE promotes cell proliferation and tumorigenicity in colorectal cancer. BMC cancer 20 24006921
1996 Clostridium perfringens type A enterotoxin (CPE): more than just explosive diarrhea. Critical reviews in microbiology 20 8989513
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
2020 Differentiation of Cytopathic Effects (CPE) induced by influenza virus infection using deep Convolutional Neural Networks (CNN). PLoS computational biology 17 32401790
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
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
2023 Top-Down Proteomics of Mouse Islets With Beta Cell CPE Deletion Reveals Molecular Details in Prohormone Processing. Endocrinology 10 37967211
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 10 36549463
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
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 9 25461607
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
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
2025 First genomic analysis of a Clostridium perfringens strain carrying both the cpe and netB genes and the proposal of an amended toxin-based typing scheme. Frontiers in microbiology 5 40458709
2022 CPE Regulates Proliferation and Apoptosis of Primary Myocardial Cells Mediated by Ischemia and Hypoxia Injury. Journal of healthcare engineering 5 35340224
2021 Ablation of Red Stable Transfected Claudin Expressing Canine Prostate Adenocarcinoma and Transitional Cell Carcinoma Cell Lines by C-CPE Gold-Nanoparticle-Mediated Laser Intervention. International journal of molecular sciences 5 34830170
2015 Oncoleaking: Use of the Pore-Forming Clostridium perfringens Enterotoxin (CPE) for Suicide Gene Therapy. Methods in molecular biology (Clifton, N.J.) 5 26072402

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