Affinage

CKAP4

Cytoskeleton-associated protein 4 · UniProt Q07065

Length
602 aa
Mass
66.0 kDa
Annotated
2026-04-28
100 papers in source corpus 15 papers cited in narrative 15 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CKAP4 (CLIMP-63) is a type II transmembrane protein that organizes ER architecture and functions as a cell-surface signaling receptor. Its luminal coiled-coil domain forms oligomeric rods that specify rough ER sheet morphology and peripheral tubule nanodomain organization, while its cytoplasmic domain anchors the ER to microtubules during interphase — an interaction abolished by mitotic phosphorylation of Ser-3/17/19 (PMID:11402071, PMID:15703217, PMID:31469817). At the plasma membrane, palmitoylation-dependent CKAP4 serves as a high-affinity receptor for DKK1, coupling ligand binding through its proline-rich domain to PI3K (via SH3-domain engagement) and AKT activation to drive proliferation and angiogenesis; DKK1 binding triggers depalmitoylation and formation of a ternary DKK1–CKAP4–LRP5/6 complex (PMID:27322059, PMID:31744930, PMID:34079085). CKAP4 additionally regulates α5β1 integrin recycling through SNX17 to control cell migration, interacts with the lncRNA SENCR to stabilize CDH5-based adherens junctions in endothelial cells, and is secreted in exosomes where it mediates intercellular WNT3A signaling and transfer of membrane mechanical properties (PMID:31160493, PMID:30584103, PMID:34671013, PMID:35412892).

Mechanistic history

Synthesis pass · year-by-year structured walk · 9 steps
  1. 2001 High

    Establishing how CKAP4 achieves ER subdomain-specific localization resolved a key question about ER sheet identity: the luminal coiled-coil domain forms 91-nm oligomeric rods that restrict lateral diffusion and exclude the protein from the nuclear envelope.

    Evidence Mutagenesis, FRAP, immuno-EM, CD spectroscopy, and analytical ultracentrifugation of recombinant luminal domain in COS-7 and HeLa cells

    PMID:11402071

    Open questions at the time
    • Whether the luminal oligomers bridge opposing ER membranes to set sheet thickness was not resolved
    • No identification of accessory factors that might nucleate or regulate oligomerization
  2. 2005 High

    Demonstrating that mitotic phosphorylation of cytoplasmic Ser-3/17/19 abolishes microtubule binding established how ER-microtubule anchoring is cell-cycle regulated, explaining ER collapse around the nucleus during mitosis.

    Evidence 32P metabolic labeling, phospho-mimetic and phospho-null mutants, in vitro microtubule binding assays, live-cell ER imaging

    PMID:15703217

    Open questions at the time
    • Kinase(s) responsible for mitotic phosphorylation were not identified
    • Whether dephosphorylation after mitosis is sufficient for ER redistribution was not tested
  3. 2010 Medium

    Identification of CKAP4 as a receptor for surfactant protein-A on type II pneumocytes and as a palmitoylation-dependent gentamicin-binding protein established that CKAP4 functions at the plasma membrane as a ligand-responsive receptor beyond its ER role.

    Evidence SP-A receptor binding studies and clathrin-dependent endocytosis analysis; gentamicin-agarose pulldown/MS, palmitoylation mutagenesis, and apoptosis assays in kidney proximal tubule cells

    PMID:20054143 PMID:21368867

    Open questions at the time
    • SP-A evidence cited from a review rather than primary binding data
    • Whether SP-A and gentamicin share a binding site on CKAP4 was not determined
    • 14-3-3 interaction with CKAP4 was not further mechanistically dissected
  4. 2012 Medium

    Discovery that CKAP4 forms an RNA-independent complex with Dicer and stabilizes Dicer protein levels revealed an unexpected role in miRNA biogenesis.

    Evidence Yeast two-hybrid, co-IP, in vitro pre-miRNA processing assay, siRNA knockdown with Dicer stability measurement

    PMID:23047949

    Open questions at the time
    • Interaction mapped to luminal domain raises topology questions for cytoplasmic Dicer
    • Not independently replicated
    • Scope of miRNAs affected beyond HMGA2 regulation unknown
  5. 2016 High

    Identification of CKAP4 as a DKK1 receptor that activates PI3K/AKT via its proline-rich domain fundamentally reframed CKAP4 as a signaling receptor and revealed a DKK1 pathway parallel to canonical LRP6-mediated Wnt inhibition.

    Evidence Co-IP, pulldown assays, binding affinity measurements, domain mutagenesis, in vitro PI3K-AKT activation, xenograft tumor models, and anti-CKAP4 antibody blockade

    PMID:27322059

    Open questions at the time
    • Crystal structure of DKK1–CKAP4 interface not determined
    • Relative contributions of CKAP4 vs. LRP6 pathways in normal tissue homeostasis unclear
  6. 2019 High

    Multiple studies in 2019 expanded CKAP4's plasma-membrane and exosomal functions: palmitoylation-regulated DRM localization enables ternary DKK1–CKAP4–LRP5/6 complex formation; CKAP4 controls α5β1 integrin recycling through SNX17 independently of DKK1; CKAP4-bearing exosomes transfer membrane stiffness gradients and migratory potential; and CKAP4 organizes peripheral ER tubule nanodomains alongside RTN4a.

    Evidence DRM fractionation, palmitoylation assays, APT inhibitor studies (palmitoylation); co-IP with β1 integrin and SNX17, surface biotinylation, integrin recycling assays (integrin axis); AFM stiffness mapping, exosome transfer, in vivo metastasis (exosomes); STED super-resolution imaging with knockdown/overexpression (ER nanodomains)

    PMID:31160493 PMID:31469817 PMID:31744930 PMID:35412892

    Open questions at the time
    • Whether integrin recycling function and DKK1 signaling are coordinated at the same membrane pool is unknown
    • Structural basis for SNX17–CKAP4 interaction not defined
    • How CKAP4 is selected for exosome loading is not fully characterized
  7. 2019 High

    Exosomal CKAP4 secretion was shown to be DKK1-dependent and required exosome biogenesis machinery, while anti-CKAP4 monoclonal antibodies suppressed pancreatic tumor growth, validating CKAP4 as a therapeutic target.

    Evidence Exosome isolation, serum CKAP4 ELISA, anti-CKAP4 mAb blockade, AKT assays, xenograft and orthotopic tumor models in mice

    PMID:30610103

    Open questions at the time
    • Whether anti-CKAP4 antibodies affect normal tissue signaling not assessed
    • Minimal residual disease and resistance mechanisms not studied
  8. 2021 Medium

    CKAP4 was placed in paracrine signaling circuits: DKK1–CKAP4–PI3K/AKT drives PLVAP-dependent angiogenesis in cholangiocarcinoma, and GOLPH3 redirects CKAP4 from the plasma membrane to exosomes to enhance exosomal WNT3A secretion and β-catenin signaling.

    Evidence CCA–endothelial co-culture with PI3K inhibitors (PLVAP); IP-MS of GOLPH3–CKAP4, surface/exosome fractionation, Wnt reporter assays, in vivo metastasis (WNT3A)

    PMID:34079085 PMID:34671013

    Open questions at the time
    • Whether GOLPH3-mediated CKAP4 redistribution affects ER morphology is unknown
    • Endothelial CKAP4 expression regulation in normal vasculature not addressed
  9. 2018 High

    Discovery that CKAP4 binds the lncRNA SENCR and that SENCR depletion causes CKAP4 surface accumulation, disrupting CDH5/CTNND1 adherens junctions, established a non-coding RNA-dependent mechanism for endothelial barrier regulation.

    Evidence Biotinylated RNA pulldown/MS, reciprocal RIP, SENCR knockdown with surface fractionation, CDH5 co-IP, endothelial permeability assays

    PMID:30584103

    Open questions at the time
    • How SENCR binding retains CKAP4 intracellularly is mechanistically undefined
    • Whether other lncRNAs similarly regulate CKAP4 distribution is unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis for DKK1–CKAP4 and PI3K–CKAP4 interactions, the identity of kinases phosphorylating Ser-3/17/19 during mitosis, how CKAP4 is partitioned between ER sheets, plasma membrane, and exosomes, and whether ER-morphogenetic and signaling receptor functions are coordinated or independent.
  • No high-resolution structure of CKAP4 or its complexes
  • Kinase identity for mitotic phosphorylation unknown
  • Mechanisms governing CKAP4 ER-to-PM trafficking not defined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 4 GO:0003723 RNA binding 2 GO:0008092 cytoskeletal protein binding 1 GO:0060090 molecular adaptor activity 1
Localization
GO:0005886 plasma membrane 5 GO:0005576 extracellular region 3 GO:0005783 endoplasmic reticulum 3 GO:0031410 cytoplasmic vesicle 3
Pathway
R-HSA-162582 Signal Transduction 3 R-HSA-1852241 Organelle biogenesis and maintenance 3 R-HSA-5653656 Vesicle-mediated transport 3 R-HSA-1500931 Cell-Cell communication 1 R-HSA-1640170 Cell Cycle 1
Partners
CDH5DICER1DKK1GOLPH3ITGB1LRP6SENCRSNX17
Complex memberships
DKK1-CKAP4-LRP5/6 ternary complex

Evidence

Reading pass · 15 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2016 CKAP4 was identified as a receptor for DKK1 (Dickkopf1). DKK1 binds CKAP4 at the plasma membrane with affinity similar to LRP6 but via different cysteine-rich domains. DKK1 binding induces clathrin-dependent internalization of CKAP4. The proline-rich domain of CKAP4 interacts with the SH3 domain of PI3K, forming a complex that activates AKT and drives cell proliferation. Co-immunoprecipitation, pulldown assays, binding affinity measurements, clathrin-dependent endocytosis assays, domain mutagenesis, in vitro PI3K-AKT activation assays, xenograft tumor models, anti-CKAP4 antibody blockade The Journal of clinical investigation High 27322059
2001 CKAP4 (CLIMP-63) localizes specifically to the rough ER but is excluded from the nuclear envelope. The luminal alpha-helical segment is necessary and sufficient for ER subdomain-specific localization: it forms oligomeric 91-nm rod-like coiled-coil structures via electrostatic interactions, restricts protein diffusion within the ER membrane, and prevents nuclear envelope localization. The cytosolic domain alone does not determine this localization. Mutagenesis of luminal and cytosolic domains, confocal microscopy of living cells, immunoelectron microscopy, FRAP (photobleaching/recovery analysis), circular dichroism spectroscopy, electron microscopy of recombinant luminal segment, analytical ultracentrifugation The Journal of cell biology High 11402071
2005 CKAP4 (CLIMP-63) links the ER to microtubules via its cytoplasmic domain, and this interaction is regulated by phosphorylation. During mitosis, CKAP4 is hyperphosphorylated at serines 3, 17, and 19 in its cytoplasmic domain, abrogating microtubule binding in vitro. Phospho-mimicking mutations (S→E) cause ER collapse around the nucleus during interphase without disrupting microtubules, establishing that CKAP4-mediated ER-microtubule anchoring maintains ER distribution during interphase. Metabolic 32P labeling, site-directed mutagenesis (S3/17/19A and S3/17/19E), in vitro microtubule binding assay, overexpression of phospho-mimicking mutant with live-cell imaging of ER morphology Molecular biology of the cell High 15703217
2018 CKAP4 physically interacts with the lncRNA SENCR via a noncanonical RNA-binding domain in CKAP4. When SENCR is depleted, CKAP4 protein accumulates at the endothelial cell surface, where it associates with CDH5 (VE-cadherin), destabilizing the CDH5/CTNND1 complex and promoting CDH5 internalization, resulting in impaired adherens junctions and increased endothelial permeability. Biotinylated RNA pulldown and mass spectrometry to identify CKAP4 as SENCR-binding protein; RNA immunoprecipitation with anti-CKAP4 antibody; SENCR knockdown with surface fractionation; co-immunoprecipitation of CKAP4 with CDH5; measurement of EC permeability Proceedings of the National Academy of Sciences of the United States of America High 30584103
2019 CKAP4 palmitoylation is required for its localization to detergent-resistant membrane (DRM) fractions at the plasma membrane and for its ability to promote cell proliferation. DKK1 binding induces depalmitoylation of both CKAP4 and LRP6 by acylprotein thioesterases (APTs), causing their translocation to non-DRM fractions. DKK1 simultaneously binds CKAP4 and LRP6 to form a ternary complex, and LRP5/6 enhances DKK1-CKAP4-AKT signaling. DRM fractionation, palmitoylation assays, APT inhibitor experiments, knockdown of LRP5/6 and CKAP4, co-immunoprecipitation of ternary complex, AKT activation assays, cell proliferation assays Science signaling High 31744930
2019 CKAP4 interacts with β1 integrin and controls the recycling of α5β1 integrin to the plasma membrane independently of DKK1. CKAP4 depletion enlarges cell adhesion sites, enhances adhesion to fibronectin, and decreases cell migration by upregulating α5β1 integrin recycling. CKAP4 binds sorting nexin 17 (SNX17), a mediator of integrin recycling, and its depletion enhances recruitment of α5β1 integrin to SNX17. Co-immunoprecipitation of CKAP4 with β1 integrin and SNX17, CKAP4 knockdown, surface biotinylation to measure integrin levels, integrin internalization and recycling assays, cell adhesion and migration assays Molecular and cellular biology High 31160493
2019 CKAP4 is secreted in exosomes from pancreatic ductal adenocarcinoma cells via DKK1-dependent endocytosis routes, requiring exosome biogenesis molecules. Anti-CKAP4 monoclonal antibodies with different epitopes block DKK1-CKAP4 binding, suppress AKT activity, and inhibit cancer cell proliferation and migration in vitro, and suppress xenograft tumor formation and extend survival in mouse models. Exosome isolation and characterization, ELISA for serum CKAP4, anti-CKAP4 mAb binding inhibition assays, AKT activity assays, xenograft and intraperitoneal/orthotopic injection tumor models Clinical cancer research High 30610103
2012 CKAP4 (CLIMP-63) interacts with Dicer to form a high-molecular-weight, electrostatic, RNA-independent complex that is catalytically active in pre-microRNA processing. CLIMP-63 is required to stabilize Dicer protein levels and for optimal Dicer-mediated regulation of HMGA2 mRNA. Dicer interacts with a portion of the luminal domain of CLIMP-63, and both proteins can be co-secreted. Yeast two-hybrid screening, co-immunoprecipitation, in vitro pre-microRNA processing assay, siRNA knockdown of CLIMP-63 with Dicer protein level measurement, reporter gene assay Nucleic acids research Medium 23047949
2010 CKAP4 (P63) functions as a receptor for surfactant protein-A (SP-A) on type II pneumocytes, mediating clathrin-dependent endocytosis of surfactant. SP-A interaction with P63/CKAP4 regulates surfactant turnover in the lung alveolar space. Receptor-binding studies, SP-A-null mouse rescue experiments, endocytosis pathway analysis (clathrin-dependent vs. actin-dependent) reviewed from primary experimental literature Cellular physiology and biochemistry Medium 20054143
2010 CKAP4 (CLIMP-63) undergoes DKK1-dependent gentamicin-enhanced dimerization (DTT-resistant) in kidney proximal tubule cells, and this dimerization requires CKAP4 palmitoylation. CLIMP-63 siRNA knockdown enhances cellular resistance to gentamicin-induced apoptosis. Gentamicin also enhances the interaction between CLIMP-63 and 14-3-3 proteins, implicating this complex in aminoglycoside cytotoxicity. Gentamicin-agarose pulldown/mass spectrometry to identify CKAP4 as a gentamicin-binding protein, western blot for DTT-resistant dimers, palmitoylation mutant transfection, siRNA knockdown, apoptosis assays, co-immunoprecipitation of CLIMP-63 with 14-3-3 Cell death & disease Medium 21368867
2019 CKAP4 regulates cell mechanics by maintaining a central-to-peripheral gradient of stiffness on the bladder cancer cell membrane, promoting cell migration. This mechanical trait is transferable through exosome-mediated intercellular CKAP4 trafficking, enhancing migration in recipient cells and increasing metastatic potential in vivo. Cell-SELEX aptamer-based target discovery identifying CKAP4, atomic force microscopy for membrane stiffness measurement, CKAP4 knockdown/overexpression, exosome isolation and transfer experiments, in vivo metastasis models Proceedings of the National Academy of Sciences of the United States of America Medium 35412892
2021 CKAP4 interacts with GOLPH3 and facilitates exosomal secretion of WNT3A in non-small-cell lung cancer. GOLPH3 decreases plasma membrane-localized CKAP4 and increases exosome-localized CKAP4 to promote CKAP4-containing exosome formation, which in turn binds and enhances secretion of exosomal WNT3A to activate Wnt/β-catenin signaling and promote metastasis. Immunoprecipitation-mass spectrometry to identify GOLPH3-CKAP4 interaction, surface fraction and exosome fraction analysis, WNT3A binding assays, luciferase reporter for Wnt/β-catenin, migration/invasion assays, in vivo metastasis models Cell death & disease Medium 34671013
2021 DKK1 secreted by cholangiocarcinoma cells binds to CKAP4 on endothelial cells, activating PI3K/AKT signaling, which upregulates PLVAP expression, thereby increasing angiogenic potency of endothelial cells in a paracrine fashion. Co-culture experiments of CCA cells with endothelial cells, DKK1/CKAP4 binding assays, PI3K/AKT inhibitor studies, PLVAP expression measurement, patient-derived xenograft model with anti-PLVAP antibody Oncogene Medium 34079085
2019 CKAP4 functions as a downstream component of the RBP1 axis in oral squamous cell carcinoma, where the RBP1-CKAP4 interaction critically regulates autophagic machinery, promoting oncogenic autophagy that supports cancer cell growth, migration, and invasion. iTRAQ-based proteomics to identify RBP1, co-immunoprecipitation of RBP1 and CKAP4, RBP1/CKAP4 knockdown with autophagy inhibitor rescue experiments, xenograft tumor model Cell death & disease Low 32587255
2019 CKAP4 (CLIMP-63) and RTN4a regulate the organization of peripheral ER tubule nanodomains as visualized by STED super-resolution microscopy. CLIMP-63 associates with lumenal ER blobs and increases their length, while RTN4a segregates away from and restricts lumenal blob length. Both proteins regulate nanodomain distribution of ER-resident proteins such as calnexin and derlin-1 along peripheral tubules. STED super-resolution microscopy, live-cell high-speed STED imaging, knockdown/overexpression of RTN4a and CLIMP-63, immunolabeling of ER-resident proteins PLoS biology Medium 31469817

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 On the shoulders of giants: p63, p73 and the rise of p53. Trends in genetics : TIG 429 11818141
2014 p63(+)Krt5(+) distal airway stem cells are essential for lung regeneration. Nature 428 25383540
2000 P63 and P73: P53 mimics, menaces and more. Nature reviews. Molecular cell biology 419 11252895
2004 p63 and p73: roles in development and tumor formation. Molecular cancer research : MCR 392 15280445
2006 p63 regulates an adhesion programme and cell survival in epithelial cells. Nature cell biology 365 16715076
2002 Differential expression of p63 isoforms in normal tissues and neoplastic cells. The Journal of pathology 255 12434410
2003 Functional regulation of p73 and p63: development and cancer. Trends in biochemical sciences 247 14659698
2007 p63-associated disorders. Cell cycle (Georgetown, Tex.) 242 17224651
2018 STAT3, stem cells, cancer stem cells and p63. Cellular & molecular biology letters 217 29588647
2011 p63 is a suppressor of tumorigenesis and metastasis interacting with mutant p53. Cell death and differentiation 204 21760596
2010 p63 in epithelial survival, germ cell surveillance, and neoplasia. Annual review of pathology 189 20078223
2009 Crosstalk of Notch with p53 and p63 in cancer growth control. Nature reviews. Cancer 163 19609265
2016 CKAP4 is a Dickkopf1 receptor and is involved in tumor progression. The Journal of clinical investigation 160 27322059
2004 p63: Molecular complexity in development and cancer. Carcinogenesis 154 15033906
2002 The p63 gene in EEC and other syndromes. Journal of medical genetics 152 12070241
2004 The role of p63 in development and differentiation of the epidermis. Journal of dermatological science 151 14757276
2014 SOX2 and p63 colocalize at genetic loci in squamous cell carcinomas. The Journal of clinical investigation 147 24590290
2017 Master regulatory role of p63 in epidermal development and disease. Cellular and molecular life sciences : CMLS 136 29103147
2006 Pattern of p63 mutations and their phenotypes--update. American journal of medical genetics. Part A 135 16691622
2010 Antagonistic roles of Notch and p63 in controlling mammary epithelial cell fates. Cell death and differentiation 134 20379195
2015 Transcription factor p63 bookmarks and regulates dynamic enhancers during epidermal differentiation. EMBO reports 133 26034101
2002 p63 expression in normal skin and usual cutaneous carcinomas. Journal of cutaneous pathology 133 12358808
2000 p63 and p73 transactivate differentiation gene promoters in human keratinocytes. Biochemical and biophysical research communications 124 10873608
2013 p63 steps into the limelight: crucial roles in the suppression of tumorigenesis and metastasis. Nature reviews. Cancer 123 23344544
2015 Maintaining epithelial stemness with p63. Science signaling 122 26221054
2007 One, two, three--p53, p63, p73 and chemosensitivity. Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy 120 17287142
2009 p63 and p73 transcriptionally regulate genes involved in DNA repair. PLoS genetics 115 19816568
2019 CKAP4, a DKK1 Receptor, Is a Biomarker in Exosomes Derived from Pancreatic Cancer and a Molecular Target for Therapy. Clinical cancer research : an official journal of the American Association for Cancer Research 113 30610103
2001 Subdomain-specific localization of CLIMP-63 (p63) in the endoplasmic reticulum is mediated by its luminal alpha-helical segment. The Journal of cell biology 111 11402071
1999 Structure, function and regulation of p63 and p73. Cell death and differentiation 108 10637429
2001 p53, p63 and p73--solos, alliances and feuds among family members. Biochimica et biophysica acta 104 11825686
2000 Evolution of functions within the p53/p63/p73 family. Annals of the New York Academy of Sciences 104 11193045
2005 Phosphorylation controls CLIMP-63-mediated anchoring of the endoplasmic reticulum to microtubules. Molecular biology of the cell 103 15703217
2014 Basal cell signaling by p63 controls luminal progenitor function and lactation via NRG1. Developmental cell 95 24412575
2014 Functional interplay between MDM2, p63/p73 and mutant p53. Oncogene 95 25417702
2007 The roles of p63 in cancer. Cell cycle (Georgetown, Tex.) 92 17264676
2002 P63 gene mutations and human developmental syndromes. American journal of medical genetics 91 12357472
2018 SENCR stabilizes vascular endothelial cell adherens junctions through interaction with CKAP4. Proceedings of the National Academy of Sciences of the United States of America 86 30584103
2018 KMT2D regulates p63 target enhancers to coordinate epithelial homeostasis. Genes & development 79 29440247
2021 Puma, noxa, p53, and p63 differentially mediate stress pathway induced apoptosis. Cell death & disease 76 34193827
2007 Control of keratinocyte proliferation and differentiation by p63. Cell cycle (Georgetown, Tex.) 76 17264679
2019 Molecular Mechanisms of p63-Mediated Squamous Cancer Pathogenesis. International journal of molecular sciences 75 31340447
2020 p63-related signaling at a glance. Journal of cell science 74 32917730
2013 p63 regulates glutaminase 2 expression. Cell cycle (Georgetown, Tex.) 72 23574722
2011 Role of p63 in cancer development. Biochimica et biophysica acta 70 21515338
2014 MicroRNAs and p63 in epithelial stemness. Cell death and differentiation 68 25168241
2006 Itch/AIP4 associates with and promotes p63 protein degradation. Cell cycle (Georgetown, Tex.) 68 16861923
2011 The role of p63 in cancer, stem cells and cancer stem cells. Cellular & molecular biology letters 67 21442444
2017 A double dealing tale of p63: an oncogene or a tumor suppressor. Cellular and molecular life sciences : CMLS 64 28975366
2004 p63 expression in benign and malignant breast lesions. Histology and histopathology 58 15024707
2009 Aberrant cytoplasmic expression of p63 and prostate cancer mortality. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 57 19155438
2002 p63 expression in normal, hyperplastic and malignant breast tissues. Breast cancer (Tokyo, Japan) 56 12185332
2019 p63 at the Crossroads between Stemness and Metastasis in Breast Cancer. International journal of molecular sciences 55 31159154
2002 p63. The international journal of biochemistry & cell biology 55 11733180
2001 Roles of p63 in differentiation of Müllerian duct epithelial cells. Annals of the New York Academy of Sciences 55 11795399
2003 p73 and p63 protein stability: the way to regulate function? Biochemical pharmacology 54 14555234
2015 Pathway Regulation of p63, a Director of Epithelial Cell Fate. Frontiers in endocrinology 52 25972840
2003 Differential regulation of p63 and p73 expression. Oncogene 50 12944917
2008 Contribution of p53, p63, and p73 to the developmental diseases and cancer. Neoplasma 49 18348649
2008 Therapeutic prospects for p73 and p63: rising from the shadow of p53. Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy 49 18801697
2018 Mutant p63 Affects Epidermal Cell Identity through Rewiring the Enhancer Landscape. Cell reports 47 30566872
2007 Transcriptional programs regulated by p63 in normal epithelium and tumors. Cell cycle (Georgetown, Tex.) 47 17297308
2005 Expression of p63 in diffuse large B-cell lymphoma. Applied immunohistochemistry & molecular morphology : AIMM 47 16082248
2014 Alterations of p63 and p73 in human cancers. Sub-cellular biochemistry 46 25201187
2007 p63: defining roles in morphogenesis, homeostasis, and neoplasia of the epidermis. Molecular carcinogenesis 46 17477357
2020 Oocyte Elimination Through DNA Damage Signaling from CHK1/CHK2 to p53 and p63. Genetics 45 32273296
2022 Elucidation of CKAP4-remodeled cell mechanics in driving metastasis of bladder cancer through aptamer-based target discovery. Proceedings of the National Academy of Sciences of the United States of America 44 35412892
2022 Structural diversity of p63 and p73 isoforms. Cell death and differentiation 43 35314772
2007 Expression of p63 in thymomas and normal thymus. American journal of clinical pathology 43 17276940
2019 Reticulon and CLIMP-63 regulate nanodomain organization of peripheral ER tubules. PLoS biology 42 31469817
2019 Dynamic palmitoylation controls the microdomain localization of the DKK1 receptors CKAP4 and LRP6. Science signaling 42 31744930
2004 p73 and p63: why do we still need them? Cell cycle (Georgetown, Tex.) 41 15254416
2021 GOLPH3/CKAP4 promotes metastasis and tumorigenicity by enhancing the secretion of exosomal WNT3A in non-small-cell lung cancer. Cell death & disease 40 34671013
2007 p63, cell adhesion and survival. Cell cycle (Georgetown, Tex.) 40 17297292
2005 Expression of p63 and p73 in ameloblastomas. Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology 40 15752257
2001 CUSP/p63 expression in rat and human tissues. Journal of dermatological science 39 11532371
2019 Pioneer and repressive functions of p63 during zebrafish embryonic ectoderm specification. Nature communications 38 31296872
2019 CKAP4 Regulates Cell Migration via the Interaction with and Recycling of Integrin. Molecular and cellular biology 37 31160493
2015 P63 in health and cancer. The International journal of developmental biology 37 26374530
2015 p63 controls cell migration and invasion by transcriptional regulation of MTSS1. Oncogene 36 26119942
2006 Cytokeratin, filaggrin, and p63 expression in reepithelialization during human cutaneous wound healing. Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society 36 16476070
2012 Regulation of human Dicer by the resident ER membrane protein CLIMP-63. Nucleic acids research 35 23047949
2007 Effect of p63 expression on survival in oral squamous cell carcinoma. Cancer investigation 35 17882659
2005 P63 deficiency: a failure of lineage commitment or stem cell maintenance? The journal of investigative dermatology. Symposium proceedings 35 16363063
2010 CLIMP-63 is a gentamicin-binding protein that is involved in drug-induced cytotoxicity. Cell death & disease 34 21368867
2020 The RBP1-CKAP4 axis activates oncogenic autophagy and promotes cancer progression in oral squamous cell carcinoma. Cell death & disease 32 32587255
2016 CKAP4 is identified as a receptor for Dickkopf in cancer cells. The Journal of clinical investigation 32 27322056
2014 Regulation of p63 protein stability via ubiquitin-proteasome pathway. BioMed research international 32 24822180
2007 p63 transcriptional regulation of epithelial integrity and cancer. Cell cycle (Georgetown, Tex.) 32 17297296
2009 Copper-GHK increases integrin expression and p63 positivity by keratinocytes. Archives of dermatological research 31 19319546
2009 P63 (CKAP4) as an SP-A receptor: implications for surfactant turnover. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 31 20054143
2021 Plasmalemma vesicle-associated protein promotes angiogenesis in cholangiocarcinoma via the DKK1/CKAP4/PI3K signaling pathway. Oncogene 30 34079085
2005 Expression of p63 in reactive hyperplasias and malignant lymphomas. Journal of Korean medical science 30 16224147
2024 Alveolar regeneration by airway secretory-cell-derived p63+ progenitors. Cell stem cell 28 39232560
2015 The microRNA feedback regulation of p63 in cancer progression. Oncotarget 28 25726529
2024 Autologous transplantation of P63+ lung progenitor cells for chronic obstructive pulmonary disease therapy. Science translational medicine 27 38354225
2017 BRD4 promotes p63 and GRHL3 expression downstream of FOXO in mammary epithelial cells. Nucleic acids research 27 27980063
2007 p63, cellular senescence and tumor development. Cell cycle (Georgetown, Tex.) 26 17224650
2021 p63 and p53: Collaborative Partners or Dueling Rivals? Frontiers in cell and developmental biology 25 34291055
2015 How many lives does CLIMP-63 have? Biochemical Society transactions 25 25849921