Affinage

CP

Ceruloplasmin · UniProt P00450

Round 2 corrected
Length
1065 aa
Mass
122.2 kDa
Annotated
2026-04-28
130 papers in source corpus 15 papers cited in narrative 15 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

Ceruloplasmin (CP) is a multicopper ferroxidase that oxidizes Fe²⁺ to Fe³⁺ to regulate iron efflux from cells, and also functions as a plasma NO oxidase converting NO to nitrite, thereby maintaining both systemic iron and nitric oxide homeostasis (PMID:12055353, PMID:16906150). Loss-of-function mutations cause aceruloplasminemia, an autosomal recessive disorder of iron accumulation in brain, liver, and retina, with CP expression in CNS localized to perivascular astrocytes via a GPI-anchored splice isoform (PMID:7708681, PMID:8968753, PMID:10660599). CP transcription is induced by HIF-1α in response to hypoxia, iron depletion, and copper accumulation, and CP in turn modulates HIF-1α stability, forming a positive feedback loop that suppresses ferroptosis by limiting intracellular Fe²⁺ and lipid ROS accumulation (PMID:15741220, PMID:35101526, PMID:32283255). CP mRNA translation is post-transcriptionally silenced by the IFN-γ-activated GAIT complex, in which phosphorylated GluProRS binds the CP 3′-UTR GAIT element to repress translation via mRNA circularization (PMID:15479637, PMID:12575997).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 1984 High

    Establishing that ceruloplasmin is a single-chain glycoprotein resolved longstanding uncertainty about whether it comprised multiple subunits and provided the primary structure foundation for all subsequent functional studies.

    Evidence Complete protein sequencing of proteolytic fragments with overlap determination from purified human ceruloplasmin

    PMID:6582496

    Open questions at the time
    • Three-dimensional crystal structure not yet determined at this time
    • Copper binding sites not mapped to the primary sequence
  2. 1995 High

    Identification of loss-of-function CP mutations as the cause of aceruloplasminemia established that CP is essential for iron efflux, not merely a copper transport protein, and linked its absence to tissue iron overload and neurodegeneration.

    Evidence PCR sequencing of all 19 CP exons in aceruloplasminemia patients; MRI and liver biopsy confirming iron deposition

    PMID:7708681

    Open questions at the time
    • Mechanism by which CP mediates iron efflux at the molecular level remained unclear
    • Whether brain-specific isoforms existed was unknown
  3. 1996 High

    Localizing CP expression to perivascular astrocytes and retinal cells explained the specific neurodegeneration pattern in aceruloplasminemia and indicated a non-hepatic, CNS-autonomous role for CP in iron homeostasis.

    Evidence In situ hybridization with CP cRNA probes in human brain and retinal tissue; RNase protection assays

    PMID:8968753

    Open questions at the time
    • Whether CNS CP was membrane-anchored or secreted was unknown
    • The mechanism of CP-dependent neuronal protection was not defined
  4. 2000 High

    Discovery of a GPI-anchored CP splice isoform predominant in brain astrocytes resolved how CP could function at the cell surface to mediate local iron efflux independently of secreted hepatic ceruloplasmin.

    Evidence cDNA cloning of alternatively spliced exon downstream of exon 18; RNase protection comparing brain and liver

    PMID:10660599

    Open questions at the time
    • Whether GPI-CP and secreted CP have identical ferroxidase activity was not tested
    • Regulation of alternative splicing not addressed
  5. 2003 Medium

    Elucidation of the GAIT-element-mediated translational silencing mechanism showed that CP mRNA is post-transcriptionally regulated by IFN-γ through 3′-UTR-dependent mRNA circularization, establishing a paradigm for cytokine-regulated translational control.

    Evidence In vitro translation assays and RNA-protein binding studies with the CP 3′-UTR GAIT element

    PMID:12575997

    Open questions at the time
    • Identity of all GAIT complex components not yet known
    • Physiological significance of CP translational silencing during inflammation not demonstrated in vivo
  6. 2004 High

    Identification of phosphorylated GluProRS as a core GAIT complex component defined the molecular machinery responsible for IFN-γ-induced CP translational silencing, linking aminoacyl-tRNA synthetase moonlighting to immune-regulated gene expression.

    Evidence RNA affinity chromatography with CP GAIT element; mass spectrometry; co-immunoprecipitation; reconstituted in vitro translation

    PMID:15479637

    Open questions at the time
    • In vivo relevance of GAIT-mediated CP silencing in infection or inflammation not shown
    • Whether other mRNAs are coordinately regulated by GAIT was unknown
  7. 2005 High

    Demonstrating that copper stabilizes HIF-1α by inhibiting prolyl hydroxylases, leading to HIF-1-dependent CP transcription, unified copper, oxygen, and iron sensing into a single transcriptional regulatory pathway for CP.

    Evidence In vitro PHD hydroxylation assays with CuCl₂; HRE-reporter assays; RT-PCR in hepatoma cells and hypoxic mouse liver

    PMID:15741220

    Open questions at the time
    • Whether HIF-1α directly binds CP promoter HREs via ChIP was not shown
    • Contribution of other HIF isoforms not assessed
  8. 2006 High

    Discovery of CP's NO oxidase activity expanded its enzymatic repertoire beyond ferroxidase function and demonstrated a physiological role in maintaining plasma nitrite and protecting against ischemia-reperfusion injury.

    Evidence CP immunodepletion; Cp⁻/⁻ knockout mice; aceruloplasminemia patient plasma; NO oxidase assays; hepatic ischemia-reperfusion with nitrite rescue

    PMID:16906150

    Open questions at the time
    • Structural basis of NO oxidation versus ferroxidation not resolved
    • Relative contribution of CP versus other NO oxidases in vivo unclear
  9. 2020 High

    Connecting CP to ferroptosis suppression showed that CP's iron-regulatory function directly protects against a specific form of regulated cell death, explaining pathological consequences of CP loss beyond simple iron accumulation.

    Evidence CP knockdown/overexpression in HCC cells with erastin and RSL3; Fe²⁺ and lipid ROS quantification; pathogenic CP frameshift mutation characterization

    PMID:32283255

    Open questions at the time
    • Whether CP suppresses ferroptosis in non-cancer cell types not tested
    • Direct interaction between CP and ferroptosis machinery not identified
  10. 2022 High

    Identification of a HIF-1α/CP positive feedback loop in radioresistant HCC, where radiation-induced copper accumulation stabilizes HIF-1α which upregulates CP to suppress ferroptosis, provided a mechanistic basis for CP's role in therapy resistance.

    Evidence COMMD10 KD/OE; HIF-1α ubiquitination and nuclear translocation assays; ferroptosis markers; in vivo mouse radiotherapy models

    PMID:35101526

    Open questions at the time
    • Whether COMMD10-HIF-1α-CP axis operates in non-hepatic cancers not established
    • Direct physical interaction between CP and HIF-1α not demonstrated
  11. 2022 Medium

    Identification of Igf2bp1 as an m6A reader that stabilizes CP mRNA in activated microglia linked epitranscriptomic regulation to CP expression in neuroinflammation.

    Evidence MeRIP-seq; Igf2bp1 knockdown/overexpression with mRNA stability assays in LPS-activated microglia

    PMID:35572575

    Open questions at the time
    • Whether m6A modification of CP mRNA occurs in non-microglial cells not tested
    • Specific m6A sites on CP mRNA not mapped
    • Single-lab finding awaiting independent replication
  12. 2024 Medium

    Demonstration that lncRNA LINC02936 recruits SIX1 to the CP promoter to upregulate CP transcription and suppress ferroptosis in endometrial cancer revealed a tissue-specific transcriptional regulatory axis distinct from the HIF-1α pathway.

    Evidence ChIP; co-IP; promoter-reporter assays; KD/OE of LINC02936 and SIX1; small peptide intervention; xenograft models

    PMID:38385087

    Open questions at the time
    • Whether SIX1 regulates CP in non-cancer contexts is unknown
    • Single-lab study; independent validation needed

Open questions

Synthesis pass · forward-looking unresolved questions
  • How CP coordinates its ferroxidase and NO oxidase activities at the structural level, and whether the HIF-1α/CP feedback loop and ferroptosis suppression represent general mechanisms across tissues or are context-restricted to specific pathologies, remain unresolved.
  • Structural basis distinguishing ferroxidase versus NO oxidase active sites not defined
  • In vivo genetic validation of CP-ferroptosis axis outside liver/brain is lacking
  • Relative contribution of GPI-anchored versus secreted CP isoforms to ferroptosis suppression unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 3 GO:0016491 oxidoreductase activity 2
Localization
GO:0005576 extracellular region 3 GO:0005886 plasma membrane 1
Pathway
R-HSA-382551 Transport of small molecules 4 R-HSA-5357801 Programmed Cell Death 4 R-HSA-168256 Immune System 2 R-HSA-8953854 Metabolism of RNA 2
Partners
COMMD10EPRS1HIF1AIGF2BP1SIX1SLC7A11
Complex memberships
GAIT complex (mRNA target, not subunit)

Evidence

Reading pass · 15 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1984 Human ceruloplasmin is a single polypeptide chain of 1,046 amino acid residues (Mr ~120 kDa) with four N-linked glucosamine oligosaccharide attachment sites; the apparent subunit-like fragments (67-, 50-, and 19-kDa) arise from proteolytic cleavage during purification rather than reflecting a multi-chain structure. Protein sequencing of proteolytic fragments with overlap determination; SDS-PAGE Proceedings of the National Academy of Sciences of the United States of America High 6582496
1995 Loss-of-function mutations in the ceruloplasmin (CP) gene cause aceruloplasminemia, an autosomal recessive disorder characterized by iron accumulation in the brain (basal ganglia), liver, and retina, establishing ceruloplasmin as essential for normal iron efflux from cells with mobilizable iron stores. A 5-bp insertion in exon 7 causing a frameshift and truncated protein was identified as the causative mutation. PCR amplification and DNA sequence analysis of all 19 exons of the CP gene; Southern blotting; MRI and liver biopsy for iron deposition phenotyping Proceedings of the National Academy of Sciences of the United States of America High 7708681
1996 Ceruloplasmin gene expression is localized specifically to glial cells (astrocytes) associated with the brain microvasculature, glial cells surrounding dopaminergic neurons in the substantia nigra, and cells in the inner nuclear layer of the retina — tissues that correspond to sites of neurodegeneration in aceruloplasminemia — indicating that glial ceruloplasmin is essential for iron homeostasis and neuronal survival in the CNS. RNA blot analysis; RNase protection; biosynthetic labeling; in situ hybridization with ceruloplasmin cRNA probes in human brain and retinal tissue Human molecular genetics High 8968753
1998 Ceruloplasmin (Cp) facilitates cellular iron uptake by HepG2 hepatocytes, increasing the apparent affinity for iron substrate approximately 3-fold; Cp synthesis is transcriptionally upregulated 4–5-fold by iron depletion, establishing a transcriptional feedback loop for intracellular iron homeostasis distinct from the post-transcriptional regulation of other iron-handling proteins. Iron uptake assays with radiolabeled iron in HepG2 cells ± Cp; iron depletion/repletion experiments; transcriptional regulation assays Science High 9445478
2000 A GPI-anchored isoform of ceruloplasmin is expressed on the surface of brain astrocytes, generated by alternative RNA splicing downstream of exon 18, which replaces the C-terminal 5 amino acids of the secreted hepatocyte form with 30 amino acids that signal GPI anchor addition. The GPI-anchored form is the predominant ceruloplasmin isoform in brain, whereas the secreted form predominates in liver. cDNA cloning; RNase protection analysis comparing brain and liver; sequence analysis of alternatively spliced exon The Journal of biological chemistry High 10660599
2002 Ceruloplasmin functions as a serum ferroxidase that contains >95% of plasma copper and couples substrate (Fe2+) oxidation to the four-electron reduction of O2 to water, acting as a member of the multicopper oxidase family; its primary physiological role is determining the rate of iron efflux from cells with mobilizable iron stores (not copper transport). Review integrating biochemical assays of ferroxidase activity, aceruloplasminemia genetic studies, and multicopper oxidase family comparisons Annual review of nutrition High 12055353
2004 Interferon-gamma (IFN-γ) triggers phosphorylation of glutamyl-prolyl-tRNA synthetase (GluProRS), releasing it from the multisynthetase complex; phosphorylated GluProRS then assembles with three additional proteins into the GAIT (IFN-γ-activated inhibitor of translation) complex, which binds the ceruloplasmin (Cp) 3'-UTR GAIT element and silences Cp mRNA translation. GluProRS was identified as a GAIT complex component by RNA affinity chromatography using the Cp GAIT element as ligand. RNA affinity chromatography with Cp GAIT element; mass spectrometry identification; co-immunoprecipitation; in vitro translation assays; mutagenesis of GluProRS and GAIT element Cell High 15479637
2005 Copper stabilizes HIF-1α under normoxic conditions by inhibiting prolyl-4-hydroxylase (PHD) activity, leading to HIF-1-dependent transcriptional induction of the ceruloplasmin (CP) gene. Hypoxia also induces hepatic ceruloplasmin in vivo in mice. Both copper and hypoxia drive CP promoter activity via hypoxia-response elements (HREs) in hepatoma cells, revealing that CP is a direct HIF-1 target gene regulated by oxygen, iron, and copper status. In vitro PHD hydroxylation assays with CuCl2; HRE-dependent reporter gene assays; real-time RT-PCR of CP mRNA in hepatoma cells and hypoxic mouse liver; CuCl2 treatment experiments Blood High 15741220
2006 Ceruloplasmin functions as a NO oxidase and nitrite synthase in plasma: it oxidizes nitric oxide (NO) to NO+, which is hydrated to nitrite, thereby maintaining endocrine NO homeostasis. Plasma NO oxidase activity was decreased after ceruloplasmin immunodepletion, in ceruloplasmin knockout (Cp−/−) mice, and in people with congenital aceruloplasminemia. Cp−/− mice had substantially reduced plasma nitrite and were more susceptible to hepatic ischemia-reperfusion injury, which was rescued by nitrite repletion. Ceruloplasmin immunodepletion from plasma; Cp knockout mice; aceruloplasminemia patient plasma; NO oxidase activity assays; plasma nitrite measurement; liver ischemia-reperfusion model with nitrite rescue Nature chemical biology High 16906150
2020 Ceruloplasmin (CP) suppresses ferroptosis in hepatocellular carcinoma (HCC) cells by regulating iron homeostasis: CP depletion promotes erastin- and RSL3-induced ferroptotic cell death with accumulation of intracellular Fe2+ and lipid ROS, while CP overexpression suppresses ferroptosis. A novel frameshift mutation in CP (c.1192-1196del) found in patients with iron accumulation and neurodegeneration abolishes CP's ability to regulate iron homeostasis and ferroptosis protection. siRNA knockdown and overexpression of CP in HCC cells; ferroptosis inducers (erastin, RSL3); Fe2+ and lipid ROS measurement; patient-derived CP frameshift mutation functional characterization Cellular signalling High 32283255
2022 The m6A reader Igf2bp1 is upregulated in LPS-activated microglia and enhances m6A methylation and stability of Cp (ceruloplasmin) mRNA (and Gbp11 mRNA), thereby mediating LPS-induced microglial inflammatory activation. Perturbation of Igf2bp1 function reduces Cp mRNA stability and microglial activation. High-throughput m6A sequencing (MeRIP-seq); RNA-seq; Igf2bp1 knockdown/overexpression; qRT-PCR; mRNA stability assays in LPS-activated microglia Frontiers in immunology Medium 35572575
2022 In hepatocellular carcinoma, ionizing radiation reduces COMMD10 expression, causing intracellular copper accumulation, which stabilizes HIF1α (by impairing its ubiquitin-mediated degradation) and promotes HIF1α nuclear translocation. HIF1α then transcriptionally upregulates ceruloplasmin (CP) and SLC7A11, which jointly suppress ferroptosis and confer radioresistance. Elevated CP in turn reduces intracellular Fe2+ levels and further stabilizes HIF1α, forming a positive HIF1α/CP feedback loop. COMMD10 knockdown/overexpression; HIF1α nuclear translocation assays; ubiquitination assays; CP and SLC7A11 transcription analysis; ferroptosis markers (GSH, lipid peroxidation, MDA, Fe2+); in vivo lentivirus-modified mouse radiotherapy models Journal of hepatology High 35101526
2024 In cerebral ischemia/reperfusion injury (CIRI), HIF-1α nuclear translocation transcriptionally upregulates CP expression; elevated CP then reduces intracellular iron-dependent ferroptosis but also increases cytoplasmic HIF-1α expression while inhibiting its nuclear translocation, forming an HIF-1α/CP regulatory loop. Chrysin inhibits HIF-1α nuclear translocation, thereby suppressing CP transcription and downstream ferroptosis in CIRI. Overexpression of CP increased HIF-1α expression yet inhibited its nuclear translocation, while CP silencing promoted HIF-1α nuclear accumulation and worsened CIRI. tMCAO rat model; OGD/R in PC12 cells; transcriptomics; qRT-PCR; Western blot; HIF-1α nuclear/cytoplasmic fractionation; CP overexpression and siRNA silencing; ferroptosis marker assays Biomedicine & pharmacotherapy Medium 38555815
2024 In endometrial cancer, lncRNA LINC02936 interacts with the transcription factor SIX1 and recruits it to the CP (ceruloplasmin) promoter, upregulating CP expression, which suppresses ferroptosis and promotes cancer progression. SIX1 directly modulates CP transcription, and a small peptide blocking the LINC02936–SIX1 interaction reduces CP expression, promotes ferroptosis, and inhibits tumor growth. ChIP assay; Co-IP; promoter-reporter assays; LINC02936 and SIX1 KD/OE; ferroptosis assays; small peptide intervention; in vivo xenograft models International journal of biological sciences Medium 38385087
2003 The ceruloplasmin 3'-UTR GAIT element mediates IFN-γ-induced translational silencing of Cp mRNA through a mechanism involving mRNA circularization: 3'-UTR-binding proteins (the GAIT complex) interact with translation initiation machinery, and mRNA loop formation is required for the repression. This represents a model for 3'-UTR-mediated translational control. In vitro translation assays; RNA-protein binding studies with Cp 3'-UTR; analysis of GAIT element structure Trends in biochemical sciences Medium 12575997

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2015 The BioPlex Network: A Systematic Exploration of the Human Interactome. Cell 1118 26186194
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2003 Complete sequencing and characterization of 21,243 full-length human cDNAs. Nature genetics 754 14702039
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2002 Ceruloplasmin metabolism and function. Annual review of nutrition 674 12055353
2004 The human plasma proteome: a nonredundant list developed by combination of four separate sources. Molecular & cellular proteomics : MCP 658 14718574
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2008 Large-scale proteomics and phosphoproteomics of urinary exosomes. Journal of the American Society of Nephrology : JASN 607 19056867
2011 Modulation of innate and adaptive immune responses by tofacitinib (CP-690,550). Journal of immunology (Baltimore, Md. : 1950) 498 21383241
1995 Aceruloplasminemia: molecular characterization of this disorder of iron metabolism. Proceedings of the National Academy of Sciences of the United States of America 449 7708681
1996 Normalization and subtraction: two approaches to facilitate gene discovery. Genome research 401 8889548
2003 Translational control by the 3'-UTR: the ends specify the means. Trends in biochemical sciences 396 12575997
2005 Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry. Journal of proteome research 350 16335952
2006 Ceruloplasmin is a NO oxidase and nitrite synthase that determines endocrine NO homeostasis. Nature chemical biology 281 16906150
1995 Ziprasidone (CP-88,059): a new antipsychotic with combined dopamine and serotonin receptor antagonist activity. The Journal of pharmacology and experimental therapeutics 270 7562537
2005 Copper-dependent activation of hypoxia-inducible factor (HIF)-1: implications for ceruloplasmin regulation. Blood 267 15741220
2004 An investigation into the human serum "interactome". Electrophoresis 247 15174051
2010 Proteomics characterization of extracellular space components in the human aorta. Molecular & cellular proteomics : MCP 231 20551380
2012 Genome-wide association for abdominal subcutaneous and visceral adipose reveals a novel locus for visceral fat in women. PLoS genetics 222 22589738
2004 Noncanonical function of glutamyl-prolyl-tRNA synthetase: gene-specific silencing of translation. Cell 221 15479637
2014 Proximity biotinylation and affinity purification are complementary approaches for the interactome mapping of chromatin-associated protein complexes. Journal of proteomics 215 25281560
2011 Toward an understanding of the protein interaction network of the human liver. Molecular systems biology 207 21988832
2022 COMMD10 inhibits HIF1α/CP loop to enhance ferroptosis and radiosensitivity by disrupting Cu-Fe balance in hepatocellular carcinoma. Journal of hepatology 206 35101526
1984 Single-chain structure of human ceruloplasmin: the complete amino acid sequence of the whole molecule. Proceedings of the National Academy of Sciences of the United States of America 195 6582496
1993 Amino-aromatic interaction between histidine 197 of the neurokinin-1 receptor and CP 96345. Nature 192 8384323
1995 The anti-emetic effects of CP-99,994 in the ferret and the dog: role of the NK1 receptor. British journal of pharmacology 182 7544198
2000 Alternative RNA splicing generates a glycosylphosphatidylinositol-anchored form of ceruloplasmin in mammalian brain. The Journal of biological chemistry 164 10660599
2007 Integral and associated lysosomal membrane proteins. Traffic (Copenhagen, Denmark) 163 17897319
1998 Role of ceruloplasmin in cellular iron uptake. Science (New York, N.Y.) 162 9445478
2003 CP-346086: an MTP inhibitor that lowers plasma cholesterol and triglycerides in experimental animals and in humans. Journal of lipid research 157 12837854
2004 Screening for N-glycosylated proteins by liquid chromatography mass spectrometry. Proteomics 156 14760718
2002 Characterization of the p53-rescue drug CP-31398 in vitro and in living cells. Oncogene 147 11948395
2020 Ceruloplasmin suppresses ferroptosis by regulating iron homeostasis in hepatocellular carcinoma cells. Cellular signalling 144 32283255
1996 Expression of the ceruloplasmin gene in the human retina and brain: implications for a pathogenic model in aceruloplasminemia. Human molecular genetics 142 8968753
2013 In-depth proteomic analyses of exosomes isolated from expressed prostatic secretions in urine. Proteomics 138 23533145
2003 CP-31398, a novel p53-stabilizing agent, induces p53-dependent and p53-independent glioma cell death. Oncogene 138 14614447
2008 Free copper, ferroxidase and SOD1 activities, lipid peroxidation and NO(x) content in the CSF. A different marker profile in four neurodegenerative diseases. Neurochemical research 137 18307039
2003 Stabilization of p53 by CP-31398 inhibits ubiquitination without altering phosphorylation at serine 15 or 20 or MDM2 binding. Molecular and cellular biology 130 12612087
1997 Antinociceptive activity of CP-101,606, an NMDA receptor NR2B subunit antagonist. British journal of pharmacology 115 9384494
1994 Development of cross-tolerance between delta 9-tetrahydrocannabinol, CP 55,940 and WIN 55,212. The Journal of pharmacology and experimental therapeutics 107 7996450
2005 Antiangiogenic and antitumor activity of a selective PDGFR tyrosine kinase inhibitor, CP-673,451. Cancer research 100 15705896
2016 Exogenous application of double-stranded RNA molecules from TMV p126 and CP genes confers resistance against TMV in tobacco. Planta 88 27456838
1996 S100 protein CP-10 stimulates myeloid cell chemotaxis without activation. Journal of cellular physiology 87 8592003
2003 The pharmacology of CP-154,526, a non-peptide antagonist of the CRH1 receptor: a review. CNS drug reviews 85 12595912
1997 Induction of the S100 chemotactic protein, CP-10, in murine microvascular endothelial cells by proinflammatory stimuli. Blood 85 9389698
2002 Antinociceptive, behavioural and neuroendocrine effects of CP 55,940 in young rats. Brain research. Developmental brain research 73 12101025
1996 Induction of the chemotactic S100 protein, CP-10, in monocyte/macrophages by lipopolysaccharide. Blood 72 8611721
2007 Discovery and pharmacologic characterization of CP-724,714, a selective ErbB2 tyrosine kinase inhibitor. Cancer research 68 17942920
2010 Treating inflammation with the Janus kinase inhibitor CP-690,550. Trends in pharmacological sciences 67 21144599
2017 LncRNA AB073614 regulates proliferation and metastasis of colorectal cancer cells via the PI3K/AKT signaling pathway. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 64 28738539
2005 Effects of JAK3 inhibition with CP-690,550 on immune cell populations and their functions in nonhuman primate recipients of kidney allografts. Transplantation 64 16314797
2003 CP-481,715, a potent and selective CCR1 antagonist with potential therapeutic implications for inflammatory diseases. The Journal of biological chemistry 63 12909630
2019 Formation of soy protein isolate (SPI)-citrus pectin (CP) electrostatic complexes under a high-intensity ultrasonic field: Linking the enhanced emulsifying properties to physicochemical and structural properties. Ultrasonics sonochemistry 62 31473418
1998 Cardiovascular disease in the JCR:LA-cp rat. Molecular and cellular biochemistry 62 9823017
2004 Comparison of renal morphology in the Streptozotocin and the SHR/N-cp models of diabetes. Laboratory investigation; a journal of technical methods and pathology 61 14767489
1993 Conformationally restricted sumatriptan analogues, CP-122,288 and CP-122,638 exhibit enhanced potency against neurogenic inflammation in dura mater. Brain research 61 8281439
2016 Selective amplification and sequencing of cyclic phosphate-containing RNAs by the cP-RNA-seq method. Nature protocols 54 26866791
2015 Dose-dependent teratogenicity of the synthetic cannabinoid CP-55,940 in mice. Neurotoxicology and teratology 50 26708672
1991 Effect of CP-96,345, a nonpeptide substance P receptor antagonist, on salivation in rats. Proceedings of the National Academy of Sciences of the United States of America 47 1719543
2020 Potent Inhibition of Thioredoxin Reductase by the Rh Derivatives of Anticancer M(arene/Cp*)(NHC)Cl2 Complexes. Inorganic chemistry 46 32073260
2002 Functional characterization of CP-465,022, a selective, noncompetitive AMPA receptor antagonist. Neuropharmacology 46 11804610
2017 Weakly Coordinating, Ketone-Directed Cp*Co(III)-Catalyzed C-H Allylation on Arenes and Indoles. Organic letters 45 29256613
2014 Investigation of the in vitro toxicological properties of the synthetic cannabimimetic drug CP-47,497-C8. Toxicology and applied pharmacology 44 24686252
2018 LncRNA AB073614 induces epithelial- mesenchymal transition of colorectal cancer cells via regulating the JAK/STAT3 pathway. Cancer biomarkers : section A of Disease markers 41 29439310
2018 A Modified Compound From Paeoniflorin, CP-25, Suppressed Immune Responses and Synovium Inflammation in Collagen-Induced Arthritis Mice. Frontiers in pharmacology 40 29930509
2011 Metabolism and accumulation of the lipophilic deoxynucleoside analogs elacytarabine and CP-4126. Investigational new drugs 40 22002019
1983 Pneumococcal bacteriophage Cp-1 contains a protein bound to the 5' termini of its DNA. Virology 40 6308899
2003 The KH-domain protein alpha CP has a direct role in mRNA stabilization independent of its cognate binding site. Molecular and cellular biology 38 12556474
2003 The biological and biochemical effects of CP-654577, a selective erbB2 kinase inhibitor, on human breast cancer cells. Cancer research 38 12907618
2008 Suppression of familial adenomatous polyposis by CP-31398, a TP53 modulator, in APCmin/+ mice. Cancer research 36 18794156
1996 Functional chemotactic factor CP-10 and MRP-14 are abundant in murine abscesses. Infection and immunity 36 8606099
1997 Regulation of EBNA gene transcription in lymphoblastoid cell lines: characterization of sequences downstream of BCR2 (Cp). Journal of virology 34 8985330
2015 The role of nicotine, cotinine and caffeine on the electrochemical behavior and bacterial colonization to cp-Ti. Materials science & engineering. C, Materials for biological applications 33 26249572
2010 Figitumumab (CP-751,871) for cancer therapy. Expert opinion on biological therapy 33 20175655
1996 Transcription of the Epstein-Barr virus nuclear antigen 1 (EBNA1) gene occurs before induction of the BCR2 (Cp) EBNA gene promoter during the initial stages of infection in B cells. Journal of virology 33 8648690
2006 Janus kinase 3 inhibition with CP-690,550 prevents allograft vasculopathy. Transplant international : official journal of the European Society for Organ Transplantation 32 17081232
2005 Effects of CP 154,526, a CRF1 receptor antagonist, on behavioral responses to cocaine in rats. Neuropeptides 31 16139885
2002 PET imaging of brain acetylcholinesterase using [11C]CP-126,998, a brain selective enzyme inhibitor. Synapse (New York, N.Y.) 30 12112408
1996 Molecular genetic analysis of Epstein-Barr virus Cp promoter function. Journal of virology 30 8627690
2022 m6A Reader Igf2bp1 Regulates the Inflammatory Responses of Microglia by Stabilizing Gbp11 and Cp mRNAs. Frontiers in immunology 28 35572575
2007 Phase I evaluation of the safety, pharmacokinetics and pharmacodynamics of CP-481,715. Clinical pharmacokinetics 28 17713973
2000 Investigations into a biomimetic approach toward CP-225,917 and CP-263,114. The Journal of organic chemistry 28 10813939
1992 CP-96,345 antagonism of NK1 receptors and smoke-induced protein extravasation in relation to its cardiovascular effects. European journal of pharmacology 28 1280591
1984 Vibrio cholerae bacteriophage CP-T1: characterization of bacteriophage DNA and restriction analysis. Journal of virology 28 6328035
2004 Alpha CP-4, encoded by a putative tumor suppressor gene at 3p21, but not its alternative splice variant alpha CP-4a, is underexpressed in lung cancer. Cancer research 27 15205328
2021 Selectively Targeting Tumor Hypoxia With the Hypoxia-Activated Prodrug CP-506. Molecular cancer therapeutics 26 34625504
2015 Real-time imaging of anti-biofilm effects using CP-OCT. Biotechnology and bioengineering 25 26156808
2007 Effect of CP-96,345 on the expression of adhesion molecules in acute pancreatitis in mice. American journal of physiology. Gastrointestinal and liver physiology 25 17218475
1995 Effects of selective activation of the 5-HT1B receptor with CP-94,253 on sleep and wakefulness in the rat. Neuropharmacology 25 8788962
2016 Knockdown of long noncoding RNA AB073614 inhibits glioma cell proliferation and migration via affecting epithelial-mesenchymal transition. European review for medical and pharmacological sciences 24 27775800
2021 Effects of Age, Diet CP, NDF, EE, and Starch on the Rumen Bacteria Community and Function in Dairy Cattle. Microorganisms 23 34442867
2018 Immunomodulatory Effects of CP-25 on Splenic T Cells of Rats with Adjuvant Arthritis. Inflammation 23 29473135
2022 In Vitro Digestion and Storage Stability of β-Carotene-Loaded Nanoemulsion Stabilized by Soy Protein Isolate (SPI)-Citrus Pectin (CP) Complex/Conjugate Prepared with Ultrasound. Foods (Basel, Switzerland) 22 36010417
2011 Candidate genes and risk for CP: a population-based study. Pediatric research 22 21857382
2004 CP-31398, a putative p53-stabilizing molecule tested in mammalian cells and in yeast for its effects on p53 transcriptional activity. Journal of negative results in biomedicine 22 15548325
2012 Molecular evolution and phylogeography of potato virus Y based on the CP gene. The Journal of general virology 21 22837421
2009 Characterization of the 5'- and 3'-terminal subgenomic RNAs produced by a capillovirus: Evidence for a CP subgenomic RNA. Virology 21 19155038
2000 CP-101606 Pfizer Inc. Current opinion in investigational drugs (London, England : 2000) 21 11249721
1971 Comparison of Bacillus cereus bacteriophages CP-51 and CP-53. Journal of virology 21 5000543
2021 CP-25 ameliorates methotrexate induced nephrotoxicity via improving renal apoptosis and methotrexate excretion. Journal of pharmacological sciences 20 33858651
2019 Regulation of CP-25 on P-glycoprotein in synoviocytes of rats with adjuvant arthritis. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 19 31521892
2006 Field Trials of Plum Clones Transformed with the Plum pox virus Coat Protein (PPV-CP) Gene. Plant disease 19 30781292
2004 Antitussive activity of the tachykinin NK1 receptor antagonist, CP-99994, in dogs. European journal of pharmacology 19 14757157
1992 Species-related differences in the electrophoretic behavior of CP 29 and CP 26: An immunochemical analysis. Photosynthesis research 19 24408776
2008 Previous maternal chemotherapy by cyclophosphamide (Cp) causes numerical chromosome abnormalities in preimplantation mouse embryos. Reproductive toxicology (Elmsford, N.Y.) 18 18930809
2005 Mutant p53 melanoma cell lines respond differently to CP-31398-induced apoptosis. The British journal of dermatology 18 16225598
1992 Genetically obese rats with (SHR/N-cp) and without diabetes (LA/N-cp) share abnormal islet responses to glucose. Metabolism: clinical and experimental 18 1406299
1985 Bacteriophage CP-T1 of Vibrio cholerae. Identification of the cell surface receptor. European journal of biochemistry 18 4065151
2024 Novel LncRNA LINC02936 Suppresses Ferroptosis and Promotes Tumor Progression by Interacting with SIX1/CP Axis in Endometrial Cancer. International journal of biological sciences 17 38385087
2024 Chrysin inhibits ferroptosis of cerebral ischemia/reperfusion injury via regulating HIF-1α/CP loop. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 17 38555815
2018 Sex differences in antinociceptive response to Δ-9-tetrahydrocannabinol and CP 55,940 in the mouse formalin test. Neuroreport 17 29461336
2015 Decrease in APP and CP mRNA expression supports impairment of iron export in Alzheimer's disease patients. Biochimica et biophysica acta 17 26209012
2014 Detection of circular permutations within protein structures using CE-CP. Bioinformatics (Oxford, England) 17 25505094
1994 Cardiovascular effects of CP-96,345, a non-peptide blocker of tachykinin NK1 receptors. European journal of pharmacology 17 8162950
2023 Excitotoxic glutamate levels drive spinal cord ependymal stem cell proliferation and fate specification through CP-AMPAR signaling. Stem cell reports 16 36764296
2020 SOX9 represses hepatitis B virus replication through binding to HBV EnhII/Cp and inhibiting the promoter activity. Antiviral research 16 32147495
2018 In vitro cell response on CP-Ti surfaces functionalized with TGF-β1 inhibitory peptides. Journal of materials science. Materials in medicine 16 29796827
2018 Inhibition of PDGFR by CP-673451 induces apoptosis and increases cisplatin cytotoxicity in NSCLC cells via inhibiting the Nrf2-mediated defense mechanism. Toxicology letters 16 29857117
2017 Long noncoding RNA AB073614 promotes the malignance of glioma by activating Wnt/β-catenin signaling through downregulating SOX7. Oncotarget 16 29029454
2017 Synthesis of Organophosphorus Compounds through Copper-Catalyzed Annulation Involving C-O and C-P Bond Formations. The Journal of organic chemistry 15 29025263
2010 Protective effects of kappa-ca3000+CP against ultraviolet-induced damage in HaCaT and MEF cells. Journal of photochemistry and photobiology. B, Biology 15 20638296
2004 The JCR:LA-cp rat: a novel model for impaired wound healing. Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society 15 14974969
1995 Chromosomal locations of the genes for the beaded filament proteins CP 115 and CP 47. Current eye research 15 7720401
2020 Neuropathophysiological significance of the c.1449T>C/p.(Tyr64Cys) mutation in the CDC42 gene responsible for Takenouchi-Kosaki syndrome. Biochemical and biophysical research communications 14 32819561
2020 Transformations of the cyclo-P4 ligand in [Cp'''Co(η4-P4)]. Chemical science 14 34094126
2018 Elevated seminal plasma estradiol and epigenetic inactivation of ESR1 and ESR2 is associated with CP/CPPS. Oncotarget 13 29731970
2016 Genetic diversity and molecular evolution of arabis mosaic virus based on the CP gene sequence. Archives of virology 13 26758729
2007 The molecular design of a recombinant antimicrobial peptide CP and its in vitro activity. Protein expression and purification 13 17988890
2002 Studies on the biosynthesis of phomoidride B (CP-263,114): evidence for a decarboxylative homodimerization pathway. Organic letters 13 11975600