Affinage

SLURP1

Secreted Ly-6/uPAR-related protein 1 · UniProt P55000

Length
103 aa
Mass
11.2 kDa
Annotated
2026-06-10
100 papers in source corpus 18 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

SLURP-1 is a secreted Ly-6/uPAR-related protein expressed as a late differentiation marker in the granular layer of epidermis and mucosal epithelia (skin, gums, stomach, esophagus, cornea) and released into biological fluids, where it governs keratinocyte and epithelial homeostasis, differentiation, proliferation, and inflammation (PMID:17008884, PMID:14721776). Loss-of-function mutations in SLURP1 cause the autosomal recessive palmoplantar keratoderma Mal de Meleda, with most disease alleles abolishing protein expression, integrity, or stability (PMID:11285253, PMID:17008884); Slurp1-deficient mice recapitulate the keratoderma with increased keratinocyte proliferation and a water-barrier defect, together with metabolic and neuromuscular abnormalities (PMID:24499735). Mechanistically, SLURP-1 is a ligand and allosteric modulator of multiple nicotinic acetylcholine receptor (nAChR) subtypes: it engages keratinocyte nAChR to promote caspase-dependent apoptosis and induce differentiation markers (PMID:16354194), and the chemically synthesized protein inhibits α3β4, α4β4, α3β2, and α9α10 nAChRs while modulating α7-nAChR only allosterically (PMID:29192197). Signaling through α7-nAChR drives NF-κB activation via complementary Ca2+-dependent CaMKII/PKC and Ca2+-independent Jak2 pathways that converge on the Raf-1/MEK1/ERK1/2 cascade (PMID:20660165). Independently of receptor signaling, SLURP-1 acts as a soluble scavenger of urokinase-type plasminogen activator (uPA), binding uPA directly to reduce cell-surface uPA and suppress epithelial proliferation and migration (PMID:25168896). It also exerts anti-inflammatory and anti-angiogenic functions by blocking NF-κB nuclear translocation through elevated cytosolic IκB, stabilizing epithelial junctions, and suppressing cytokine output (PMID:28803936, PMID:31387745), displays direct antimicrobial activity against S. aureus (PMID:26474319), and exhibits anti-malignant activity across oral, pancreatic, lung, and colorectal cancer models (PMID:17280689, PMID:29545933, PMID:32106059, PMID:39840525). SLURP1 transcription is controlled by KLF4 in cornea, by STAT3 downstream of IL-22, and by p53-mediated repression relieved through the MAPK14 axis (PMID:23139280, PMID:26474319, PMID:39840525).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 2001 High

    Establishing the disease gene was the first step: it was unknown what caused Mal de Meleda, and identifying loss-of-function SLURP1 mutations defined the gene as essential for palmoplantar epidermal integrity.

    Evidence Genetic mapping and identification of deletion, nonsense, and splice-site mutations in 19 affected families

    PMID:11285253

    Open questions at the time
    • Did not establish the molecular function of SLURP-1 or its target receptors
    • No tissue distribution or secretion data
  2. 2003 Medium

    Defined where SLURP-1 acts and how its expression is controlled, localizing it to stratified epithelia and showing secretion of a 9 kDa protein under regulation by retinoic acid, EGF, and IFN-γ.

    Evidence Immunohistochemistry, western blot of keratinocyte conditioned medium, mRNA regulation studies

    PMID:14721776

    Open questions at the time
    • No receptor or downstream signaling mechanism identified
    • Single-lab localization
  3. 2005 High

    Provided the first molecular mechanism by showing SLURP-1 binds keratinocyte nAChR at the ligand-binding site as an allosteric agonist driving apoptosis and differentiation, linking receptor engagement to the epidermal phenotype.

    Evidence Radioligand binding, caspase activity assays, TUNEL, RT-PCR with recombinant SLURP-1 and carbachol augmentation

    PMID:16354194

    Open questions at the time
    • Did not resolve which specific nAChR subunits are engaged
    • Downstream signaling cascade not mapped
  4. 2006 High

    Connected genotype to protein loss, confirming SLURP-1 as a late granular-layer differentiation marker secreted into fluids and showing that MDM mutations abolish detectable protein.

    Evidence IHC, immunoblot of biological fluids, transfection of HEK293T with mutant SLURP1 constructs

    PMID:17008884

    Open questions at the time
    • Mechanism by which protein loss causes hyperkeratosis not addressed
  5. 2007 Medium

    Extended SLURP-1's reach beyond skin, identifying immune-cell expression and α7-nAChR-coupled Ca2+ signaling and showing it prevents nitrosamine-induced malignant transformation of oral keratinocytes.

    Evidence RT-PCR tissue profiling, intracellular Ca2+ assays in T cells, soft-agar and nude-mouse xenograft assays with nAChR siRNA

    PMID:17280689 PMID:17286989

    Open questions at the time
    • α7 binding mode (allosteric vs orthosteric) not resolved here
    • Single-lab functional assays
  6. 2010 Medium

    Dissected the α7-nAChR signaling logic, showing SLURP-1 activates NF-κB through parallel Ca2+-dependent CaMKII/PKC and Ca2+-independent Jak2 pathways converging on Raf-1/MEK1/ERK1/2; a parallel study showed functional SLURP-1 is required for T-cell activation.

    Evidence Pharmacological pathway dissection with channel blockers and kinase inhibitors; MDM patient PBMC T-cell stimulation with recombinant SLURP-1 rescue

    PMID:20660165 PMID:20854438

    Open questions at the time
    • Pathway mapped pharmacologically without genetic confirmation of each node
    • T-cell rescue from a single patient genotype
  7. 2012 High

    Identified KLF4 as a direct transcriptional activator of SLURP1 in cornea and tied SLURP1 to control of corneal inflammation, with adenoviral SLURP1 reducing neutrophil influx.

    Evidence ChIP, promoter transfection, Klf4 conditional null corneas, adenoviral Slurp1 rescue, flow cytometry

    PMID:23139280

    Open questions at the time
    • Receptor/effector mediating the anti-inflammatory effect not defined here
  8. 2014 High

    Two complementary 2014 studies established loss-of-function consequences in vivo and a receptor-independent mechanism: Slurp1-knockout mice develop keratoderma with metabolic and neuromuscular defects, and SLURP-1 was shown to directly scavenge uPA to suppress epithelial proliferation and migration.

    Evidence Two independent KO mouse lines with histology/lipid/metabolic phenotyping; ligand blot, ELISA, pull-down, stable expression, and gap-filling migration assays

    PMID:24499735 PMID:25168896

    Open questions at the time
    • Relative contribution of nAChR vs uPA-scavenging pathways to keratoderma unresolved
    • Mechanism of metabolic and neuromuscular phenotypes unexplained
  9. 2017 High

    Defined the precise pharmacology against a panel of nAChRs and added anti-angiogenic function: synthetic NMR-characterized SLURP-1 inhibits α3β4, α4β4, α3β2, and α9α10 nAChRs and modulates α7 only allosterically, and SLURP1 suppresses HUVEC tube formation by blocking NF-κB nuclear translocation.

    Evidence Chemical synthesis, NMR structure, α-bungarotoxin competition, electrophysiology; HUVEC tube formation, NF-κB localization, cytokine ELISA

    PMID:28803936 PMID:29192197

    Open questions at the time
    • Physiological concentrations at each receptor in vivo not defined
    • Link between angiogenesis suppression and receptor pharmacology not established
  10. 2019 Medium

    Refined the anti-inflammatory mechanism, showing SLURP1 overexpression stabilizes epithelial junctions and suppresses TNF-α-driven cytokines through IκB-mediated blockade of NF-κB nuclear translocation.

    Evidence Stable lentiviral SLURP1 overexpression in corneal epithelial cells, RT-PCR, immunoblot, ELISA, NF-κB localization and IκB measurement

    PMID:31387745

    Open questions at the time
    • Receptor mediating junction stabilization not identified
    • Single cell-type, overexpression-based
  11. 2020 Medium

    Characterized SLURP-1 as a tumor-selective antiproliferative agent in lung adenocarcinoma acting through α7-nAChR, EGFR, and β-adrenergic receptors with IP3R/STAT3 downstream, sparing normal fibroblasts.

    Evidence Cell proliferation assays, α7-nAChR siRNA, receptor inhibitors, IP3R/STAT3 pathway analysis with recombinant SLURP-1

    PMID:32106059

    Open questions at the time
    • Multi-receptor model not deconvolved into primary target
    • Single cell line, single lab
  12. 2025 Medium

    Placed SLURP1 in a transcriptional control circuit relevant to tumor immunity, showing a MAPK14–p53 axis represses SLURP1 and that SLURP1 mediates lobeline's inhibition of M2 macrophage polarization in colorectal cancer.

    Evidence scRNA-seq, Slurp1-deficient MC38 tumor model, MAPK14 target profiling, phospho-p53 and SLURP1 transcription/secretion measurement

    PMID:39840525

    Open questions at the time
    • Receptor on macrophages mediating SLURP1 effect not identified
    • Single tumor model

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the receptor-dependent (multi-nAChR allosteric) and receptor-independent (uPA-scavenging) activities of SLURP-1 are integrated to produce the in vivo keratoderma, metabolic, and neuromuscular phenotypes remains unresolved.
  • No structural model of SLURP-1 bound to any nAChR subtype
  • Mechanism of metabolic/neuromuscular phenotypes in knockout mice unexplained
  • Primary receptor versus uPA contribution to disease not separated

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0048018 receptor ligand activity 3 GO:0098772 molecular function regulator activity 3 GO:0140313 molecular sequestering activity 1
Localization
GO:0005576 extracellular region 3
Pathway
R-HSA-168256 Immune System 3 R-HSA-112316 Neuronal System 2 R-HSA-1266738 Developmental Biology 2 R-HSA-162582 Signal Transduction 2
Partners
CHRNA7PLAU

Evidence

Reading pass · 18 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 Mutations in the SLURP1 gene (encoding SLURP-1, a secreted Ly-6/uPAR-related protein) cause Mal de Meleda (MDM), an autosomal recessive palmoplantar keratoderma. Three different homozygous loss-of-function mutations (deletion, nonsense, splice site) were identified in 19 affected families, establishing SLURP1 as the causal gene. Genetic mapping, mutation identification (deletion, nonsense, splice site mutations) in affected individuals Human molecular genetics High 11285253
2005 Recombinant SLURP-1 binds to the conventional ligand-binding site of keratinocyte nicotinic acetylcholine receptors (nAChR), showing higher affinity for the [3H]nicotine-sensitive nAChR compared to [3H]epibatidine-sensitive nAChR. SLURP-1 acts as an allosteric agonist at keratinocyte nAChR, increasing caspase-3 and caspase-8 activities, inducing apoptosis, and upregulating transglutaminase type I, cytokeratin 10, p21, and caspase-3 expression. Radioligand binding assay, caspase activity assays, TUNEL, real-time PCR, in-cell western with recombinant SLURP-1 and monoclonal antibody The Journal of investigative dermatology High 16354194
2006 SLURP1 is expressed as a late epidermal differentiation marker predominantly in the granular layer of skin (notably acrosyringium) and is secreted into biological fluids (sweat, saliva, tears, urine). MDM mutations in SLURP1 (including W15R in the signal peptide and G86R) cause absence or barely detectable protein, indicating that most MDM mutations affect SLURP1 expression, integrity, or stability. Immunohistochemistry, immunoblot of biological fluids, transfection of HEK293T cells with mutant SLURP1 constructs The Journal of investigative dermatology High 17008884
2003 SLURP-1 (ARS Component B) is localized to human skin, exocervix, gums, stomach and esophagus by immunohistochemistry. Keratinocytes underlying the stratum corneum are highly positive, and cultured keratinocytes secrete the expected 9 kDa protein. SLURP1 mRNA expression is regulated by retinoic acid, epidermal growth factor and interferon-gamma. Immunohistochemistry, western blot of cultured keratinocyte conditioned medium, mRNA regulation studies European journal of dermatology Medium 14721776
2007 SLURP-1 reportedly binds to α7 nAChRs and enhances the amplitude of macroscopic currents induced by ACh, leading to facilitation of apoptosis. SLURP-1 mRNA is expressed in immune cells including T cells, B cells, bone marrow-derived dendritic cells and macrophages. Recombinant human SLURP-1 stimulation of MOLT-3 human leukemic T cells evoked intracellular Ca2+ signaling. RT-PCR for tissue expression, intracellular Ca2+ signaling assay Life sciences Medium 17286989
2007 SLURP-1 and SLURP-2 function as autocrine and paracrine ligands of keratinocyte nAChRs; recombinant SLURP-1 preincubation considerably reduced colony formation in soft agar and tumor nodule formation in Nu/Nu mice from nitrosamine-transformed oral keratinocytes, preventing tobacco nitrosamine-induced malignant transformation. Soft agar colony formation assay, nude mouse xenograft assay, RT-PCR for SLURP expression, siRNA knockdown of nAChR subunits Life sciences Medium 17280689
2010 SLURP-1 upregulates NF-κB expression via α7-nAChR through two complementary signaling pathways: a Ca2+-entry-dependent CaMKII/PKC pathway and a Ca2+-independent Jak2 pathway, both converging on Raf-1/MEK1/ERK1/2 cascade activation. Ca2+-free medium, ion channel blockers (Cd2+, Zn2+), kinase inhibitors (MEK1, Jak2, CaMKII, PKC), mRNA and protein quantification of NF-κB American journal of physiology. Cell physiology Medium 20660165
2010 PBMCs from MDM patients with homozygous SLURP-1 G86R mutation showed impaired T-cell activation upon anti-CD3/anti-CD28 stimulation, which was restored by addition of 0.5 μg/mL recombinant human SLURP-1, establishing that functional SLURP-1 is required for normal T-cell activation. T-cell stimulation assay (anti-CD3/CD28), stimulation index measurement, rescue with recombinant SLURP-1 The British journal of dermatology Medium 20854438
2012 KLF4 transcription factor directly regulates SLURP1 expression in the cornea via binding to the SLURP1 promoter (demonstrated by ChIP and transient transfection). Klf4 conditional null (Klf4CN) corneas show significantly decreased Slurp1 with elevated cytokines and neutrophil influx. Slurp1 expression is abrogated within 24 hours of LPS injection or HSV-1/adenoviral infection, and exogenous Slurp1 expression via adenoviral vectors reduces corneal inflammation and neutrophilic infiltration. ChIP, transient transfection (promoter activity), qPCR, immunoblots, immunofluorescent staining, adenoviral Slurp1 overexpression, flow cytometry Investigative ophthalmology & visual science High 23139280
2014 Slurp1-deficient mice (Slurp1-/- and Slurp1X-/-) develop severe palmoplantar keratoderma characterized by increased keratinocyte proliferation, accumulation of lipid droplets in stratum corneum, and a water barrier defect. They also exhibit metabolic abnormalities (reduced adiposity, protection from obesity, low plasma lipid levels) and a neuromuscular abnormality (hind-limb clasping), establishing Slurp1 as required for keratinocyte homeostasis, metabolic regulation, and neuromuscular function. Knockout mouse generation (exon 2 replacement and nonsense mutation), histology, lipid analysis, metabolic phenotyping The Journal of investigative dermatology High 24499735
2014 SLURP1 modulates corneal homeostasis by acting as a soluble scavenger of urokinase-type plasminogen activator (uPA). SLURP1 directly interacts with uPA (demonstrated by ligand blots, ELISA, and pull-down assays), reduces cell surface-bound uPA at leading edges of migrating cells, and suppresses uPA-dependent corneal epithelial cell proliferation and migration. SLURP1-expressing cells fail to respond to exogenous uPA in gap-filling assays. Ligand blot, ELISA, pull-down assay, lentiviral stable expression, cell proliferation and migration assays, immunofluorescent staining Investigative ophthalmology & visual science High 25168896
2015 IL-22 upregulates SLURP1 mRNA expression in normal human epidermal keratinocytes via STAT3, as confirmed by STAT3 inhibitor and siRNA knockdown. SLURP1 significantly suppresses the growth of Staphylococcus aureus, demonstrating a direct antimicrobial activity. RT-PCR, STAT3 inhibitor treatment, siRNA knockdown of STAT3, bacterial growth assay PloS one Medium 26474319
2017 Synthetic human SLURP-1 (81 amino acids, 3D structure characterized by NMR) does not compete with [125I]-α-bungarotoxin binding to α7 or muscle-type nAChRs or AChBPs. SLURP-1 inhibits human α3β4, α4β4, α3β2, and α9α10 nAChRs, but only inhibits α7-mediated currents in the presence of the allosteric modulator PNU120596, indicating an allosteric binding mechanism. SLURP-1 inhibition of α9α10 nAChRs was accentuated at higher ACh concentrations. Chemical synthesis of SLURP-1, NMR structure determination, radioligand competition assay ([125I]-α-bungarotoxin), electrophysiology (current inhibition assays) Scientific reports High 29192197
2017 SLURP1 suppresses HUVEC tube formation by blocking nuclear translocation of NFκB. Exogenous SLURP1 suppresses TNF-α-stimulated HUVEC tube length, area, and branch points, as well as IL-8 and TNF-α production, ECM adhesion, and cell migration, without affecting cell viability or proliferation. SLURP1 expression is decreased in corneas subjected to alkali burn-induced neovascularization. HUVEC tube formation assay, NFκB nuclear localization assay, cytokine ELISA, cell adhesion assay, migration assay, QPCR/immunoblot for corneal expression Experimental eye research Medium 28803936
2018 In CHRNA7-high pancreatic cancer cell lines (COLO357, PANC-1), SLURP1 exerts anti-malignant effects through CHRNA7 (α7-nAChR) while nicotine exerts pro-malignant effects independently of CHRNA7; the two ligands act without reciprocally interfering with each other's receptor binding or downstream signaling, suggesting functional antagonism. Cell viability assays, receptor binding assays, downstream signaling analysis, CHRNA7-high cell line selection Oncotarget Medium 29545933
2019 SLURP1 overexpression in Human Corneal Limbal Epithelial (HCLE) cells upregulates expression of desmoplakin (DSP1), desmoglein (DSG1), tight junction protein (TJP1) and E-Cadherin (stabilizing epithelial cell junctions) and suppresses TNF-α-induced upregulation of IL-8, IL-1β, CXCL1 and CXCL2. The anti-inflammatory effect is mediated by suppression of NF-κB nuclear translocation via elevated cytosolic IκB. Stable SLURP1 overexpression via lentiviral vectors, RT-PCR, immunoblot, ELISA, NF-κB nuclear localization assay, IκB protein measurement Biochemical and biophysical research communications Medium 31387745
2020 Recombinant SLURP-1 (rSLURP-1) at concentrations >10 nM significantly decreases A549 lung adenocarcinoma cell growth (~70%) and fully abolishes nicotine-induced cell proliferation increase, PTEN downregulation, and α7-nAChR expression upregulation. The antiproliferative effect is mediated through α7-nAChR, EGF receptors, and β-adrenergic receptors, with downstream involvement of IP3 receptors and STAT3 transcription factor. SLURP-1 does not affect normal WI-38 fibroblast proliferation up to 1 μM. Cell proliferation assay, siRNA against α7-nAChR, pharmacological inhibitors of different receptors, IP3 receptor and STAT3 pathway analysis, co-treatment with clinical drugs International immunopharmacology Medium 32106059
2025 Slurp1 mediates anti-tumor effects of lobeline in colorectal cancer by inhibiting alternative (M2-like) activation of tumor-associated macrophages. Mechanistically, lobeline binds MAPK14 and prevents its nuclear translocation, reducing phosphorylated p53 levels, thereby relieving p53-mediated transcriptional repression of SLURP1 and increasing SLURP1 secretion. The antitumor effect is abolished in Slurp1-deficient MC38 cells. scRNA-seq, subcutaneous tumor model with Slurp1-deficient cells, target-responsive accessibility profiling (MAPK14 as lobeline target), nuclear translocation assay, phospho-p53 analysis, SLURP1 transcription/secretion measurement Advanced science Medium 39840525

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1992 The mdm-2 oncogene product forms a complex with the p53 protein and inhibits p53-mediated transactivation. Cell 3016 1535557
1993 The p53-mdm-2 autoregulatory feedback loop. Genes & development 1722 8319905
1993 Mapping of the p53 and mdm-2 interaction domains. Molecular and cellular biology 644 7686617
1994 Several hydrophobic amino acids in the p53 amino-terminal domain are required for transcriptional activation, binding to mdm-2 and the adenovirus 5 E1B 55-kD protein. Genes & development 597 7926727
2009 SoyBase, the USDA-ARS soybean genetics and genomics database. Nucleic acids research 379 20008513
1993 The mdm-2 oncogene can overcome wild-type p53 suppression of transformed cell growth. Molecular and cellular biology 343 8417333
1996 mdm-2 inhibits the G1 arrest and apoptosis functions of the p53 tumor suppressor protein. Molecular and cellular biology 333 8628312
1994 The ribosomal L5 protein is associated with mdm-2 and mdm-2-p53 complexes. Molecular and cellular biology 290 7935455
1993 The human MDM-2 oncogene is overexpressed in leukemias. Blood 273 8219216
1993 The mdm-2 gene is induced in response to UV light in a p53-dependent manner. Proceedings of the National Academy of Sciences of the United States of America 270 8265599
1988 Chromosomal ARS and CEN elements bind specifically to the yeast nuclear scaffold. Cell 223 2843296
1993 Identification and characterization of multiple mdm-2 proteins and mdm-2-p53 protein complexes. Oncogene 220 7689721
1997 Mdm-2 phosphorylation by DNA-dependent protein kinase prevents interaction with p53. Cancer research 211 9371494
1991 Mcm2 and Mcm3, two proteins important for ARS activity, are related in structure and function. Genes & development 184 2044961
2002 Mdm-2 and ubiquitin-independent p53 proteasomal degradation regulated by NQO1. Proceedings of the National Academy of Sciences of the United States of America 180 12232053
2001 Mutations in the gene encoding SLURP-1 in Mal de Meleda. Human molecular genetics 170 11285253
1993 The structure and function of yeast ARS elements. Current opinion in genetics & development 169 8274858
1998 MDM-2 oncoprotein overexpression, p53 gene mutation, and VEGF up-regulation in angiosarcomas. The American journal of pathology 150 9811333
1996 The role of arsenic-thiol interactions in metalloregulation of the ars operon. The Journal of biological chemistry 137 8621591
2005 Biological effects of SLURP-1 on human keratinocytes. The Journal of investigative dermatology 135 16354194
1993 Metalloregulated expression of the ars operon. The Journal of biological chemistry 134 8416957
1988 Sequence analysis of ARS elements in fission yeast. The EMBO journal 123 3046932
2002 Dehydroepiandrosterone inhibits human vascular smooth muscle cell proliferation independent of ARs and ERs. The Journal of clinical endocrinology and metabolism 116 11788644
2002 The muscular dystrophy with myositis (mdm) mouse mutation disrupts a skeletal muscle-specific domain of titin. Genomics 116 11829483
1983 Affinity analysis of idiotype-positive and idiotype-negative Ars-binding hybridoma proteins and Ars-immune sera. Molecular immunology 108 6843553
1995 The p53 and mdm-2 genes in human testicular germ-cell tumors. Molecular carcinogenesis 105 7893365
1996 Abnormal expression of MDM-2 in breast carcinomas. Breast cancer research and treatment 99 8750585
1989 The gene encoding ARS-binding factor I is essential for the viability of yeast. Genes & development 95 2620828
1993 A DNA unwinding element and an ARS consensus comprise a replication origin within a yeast chromosome. The EMBO journal 91 8223462
1989 Characterization of a leuA gene and an ARS element from Mucor circinelloides. Gene 88 2693214
2006 SLURP1 is a late marker of epidermal differentiation and is absent in Mal de Meleda. The Journal of investigative dermatology 83 17008884
1991 Identification and purification of a protein that binds the yeast ARS consensus sequence. Cell 82 2001590
2004 Induction and myofibrillar targeting of CARP, and suppression of the Nkx2.5 pathway in the MDM mouse with impaired titin-based signaling. Journal of molecular biology 81 14741210
2021 A new decade and new data at SoyBase, the USDA-ARS soybean genetics and genomics database. Nucleic acids research 79 33264401
2007 Immune system expression of SLURP-1 and SLURP-2, two endogenous nicotinic acetylcholine receptor ligands. Life sciences 78 17286989
1997 Molecular pathology of primary and metastatic ductal pancreatic lesions: analyses of mutations and expression of the p53, mdm-2, and p21/WAF-1 genes in sporadic and familial lesions. Cancer 75 9024708
2014 The Mdm network and its regulation of p53 activities: a rheostat of cancer risk. Human mutation 72 24488925
1997 P53, MDM-2, BAX and BCL-2 and drug resistance in chronic lymphocytic leukemia. Leukemia & lymphoma 66 9389352
1998 Leiomyosarcoma of the uterus: A clinicopathologic, DNA flow cytometric, p53, and mdm-2 analysis of 49 cases. Gynecologic oncology 64 9454661
2003 ARS Component B: structural characterization, tissue expression and regulation of the gene and protein (SLURP-1) associated with Mal de Meleda. European journal of dermatology : EJD 63 14721776
2021 Environmental eustress modulates β-ARs/CCL2 axis to induce anti-tumor immunity and sensitize immunotherapy against liver cancer in mice. Nature communications 62 34593796
2002 Expression of cell-cycle-regulated proteins pRb2/p130, p107, p27(kip1), p53, mdm-2, and Ki-67 (MIB-1) in prostatic gland adenocarcinoma. Clinical cancer research : an official journal of the American Association for Cancer Research 62 12060621
2002 Mal de Meleda (MDM) caused by mutations in the gene for SLURP-1 in patients from Germany, Turkey, Palestine, and the United Arab Emirates. Human genetics 61 12483299
1996 Analysis of the p53 and MDM-2 gene in acute myeloid leukemia. European journal of haematology 57 8898928
2010 Upregulation of nuclear factor-kappaB expression by SLURP-1 is mediated by alpha7-nicotinic acetylcholine receptor and involves both ionic events and activation of protein kinases. American journal of physiology. Cell physiology 56 20660165
2007 SLURP-1 and -2 in normal, immortalized and malignant oral keratinocytes. Life sciences 56 17280689
1997 Altered expression of p53 and mdm-2 proteins at diagnosis is associated with early treatment failure in childhood acute lymphoblastic leukemia. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 53 9060559
2014 Ars Moriendi; the art of dying well - new insights into the molecular pathways of necroptotic cell death. EMBO reports 52 24469330
2005 Mdm muscular dystrophy: interactions with calpain 3 and a novel functional role for titin's N2A domain. Human molecular genetics 48 16115818
2008 Expression of alpha-AR subtypes in T lymphocytes and role of the alpha-ARs in mediating modulation of T cell function. Neuroimmunomodulation 47 18463421
1997 Identification of autonomously replicating sequence (ARS) elements in eukaryotic cells. Methods (San Diego, Calif.) 46 9441849
2021 Treatment of ARS deficiencies with specific amino acids. Genetics in medicine : official journal of the American College of Medical Genetics 45 34194004
2010 SLURP1 mutation-impaired T-cell activation in a family with mal de Meleda. The British journal of dermatology 44 20854438
2023 Mdm-miR858 targets MdMYB9 and MdMYBPA1 to participate anthocyanin biosynthesis in red-fleshed apple. The Plant journal : for cell and molecular biology 42 36651024
1994 p53 mutations and MDM-2 amplification in renal cell cancers. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 41 7824511
2022 A cryptic transactivation domain of EZH2 binds AR and AR's splice variant, promoting oncogene activation and tumorous transformation. Nucleic acids research 40 36300627
2012 Klf4 regulates the expression of Slurp1, which functions as an immunomodulatory peptide in the mouse cornea. Investigative ophthalmology & visual science 40 23139280
1997 Amplification of the mdm-2 gene and p53 abnormalities in uterine sarcomas. International journal of cancer 40 9334806
1995 p53 and mdm-2 expression in malignant melanoma: an immunocytochemical study of expression of p53, mdm-2, and markers of cell proliferation in primary versus metastatic tumors. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 40 7675773
2021 MDM-TASK-web: MD-TASK and MODE-TASK web server for analyzing protein dynamics. Computational and structural biotechnology journal 38 34589183
2014 Palmoplantar keratoderma along with neuromuscular and metabolic phenotypes in Slurp1-deficient mice. The Journal of investigative dermatology 38 24499735
1996 Analysis of p53 and mdm-2 expression in 18 patients with Sézary syndrome. British journal of haematology 37 8616082
1995 Overexpression of MDM-2 mRNA and mutation of the p53 tumor suppressor gene in bladder carcinoma cell lines. Molecular carcinogenesis 37 7619220
1999 Adenosarcoma of the uterus: a clinicopathologic, DNA flow cytometric, p53 and mdm-2 analysis of 11 cases. International journal of gynecological cancer : official journal of the International Gynecological Cancer Society 34 11240741
2020 mdm-miR828 Participates in the Feedback Loop to Regulate Anthocyanin Accumulation in Apple Peel. Frontiers in plant science 33 33391322
1997 mdm 2 mRNA expression is associated with survival in ovarian cancer. International journal of cancer 31 9291435
1994 The mdm-2 oncogene is translocated and overexpressed in a murine plasmacytoma cell line expressing wild-type p53. Oncogene 31 8152809
2019 Potent and selective caspase-2 inhibitor prevents MDM-2 cleavage in reversine-treated colon cancer cells. Cell death and differentiation 30 30976094
2012 Structure, replication efficiency and fragility of yeast ARS elements. Research in microbiology 30 22504206
2007 Isolation and ars detoxification of arsenite-oxidizing bacteria from abandoned arsenic-contaminated mines. Journal of microbiology and biotechnology 30 18051304
2018 Small Molecule Modulators of RING-Type E3 Ligases: MDM and Cullin Families as Targets. Frontiers in pharmacology 29 29867461
2010 An invertebrate mdm homolog interacts with p53 and is differentially expressed together with p53 and ras in neoplastic Mytilus trossulus haemocytes. Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology 29 20417299
1996 Immunohistochemical and molecular evaluation of the mdm-2 gene product in bronchogenic carcinoma. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 29 8733770
2023 Mdm-miR160-MdARF17-MdWRKY33 module mediates freezing tolerance in apple. The Plant journal : for cell and molecular biology 28 36738108
2013 A small-molecule inhibitor, 5'-O-tritylthymidine, targets FAK and Mdm-2 interaction, and blocks breast and colon tumorigenesis in vivo. Anti-cancer agents in medicinal chemistry 28 22292771
2001 Do VHL and HIF-1 mirror p53 and Mdm-2? Degradation-transactivation loops of oncoproteins and tumor suppressors. Oncogene 28 11313969
2017 Mdm proteins: critical regulators of embry ogenesis and homeostasis. Journal of molecular cell biology 27 28093454
2006 Cloning and characterization of the chromosomal arsenic resistance genes from Acidithiobacillus caldus and enhanced arsenic resistance on conjugal transfer of ars genes located on transposon TnAtcArs. Microbiology (Reading, England) 27 17159207
1999 mdm-2 gene amplification in 3T3-L1 preadipocytes. Differentiation; research in biological diversity 26 10365438
1999 mdm-2 expression correlates with wild-type p53 status in esophageal adenocarcinoma. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 26 10392633
2018 Endogenous CHRNA7-ligand SLURP1 as a potential tumor suppressor and anti-nicotinic factor in pancreatic cancer. Oncotarget 25 29545933
2003 MDM-1 and MDM-2: two mutator-derived MITE families in rice. Journal of molecular evolution 25 12612829
1997 MDM-2 protein is expressed in different layers of normal human skin. Oncogene 24 9070662
2025 Targeting MAPK14 by Lobeline Upregulates Slurp1-Mediated Inhibition of Alternative Activation of TAM and Retards Colorectal Cancer Growth. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 23 39840525
2017 SLURP-1 is mutated in Mal de Meleda, a potential molecular signature for melanoma and a putative squamous lineage tumor suppressor gene. International journal of dermatology 23 29231248
2009 Antitumor activity and pharmacokinetic properties of ARS-interacting multi-functional protein 1 (AIMP1/p43). Cancer letters 23 19573982
2015 IL-22/STAT3-Induced Increases in SLURP1 Expression within Psoriatic Lesions Exerts Antimicrobial Effects against Staphylococcus aureus. PloS one 22 26474319
2014 SLURP-1 modulates corneal homeostasis by serving as a soluble scavenger of urokinase-type plasminogen activator. Investigative ophthalmology & visual science 22 25168896
2013 Nrf2 signalling promotes ex vivo tubular epithelial cell survival and regeneration via murine double minute (MDM)-2. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association 22 23476038
1995 Expression of mdm-2 and p53 protein in transitional cell carcinoma. Urological research 22 7537927
2020 Human secreted protein SLURP-1 abolishes nicotine-induced proliferation, PTEN down-regulation and α7-nAChR expression up-regulation in lung cancer cells. International immunopharmacology 21 32106059
2019 The secreted Ly-6/uPAR related protein-1 (SLURP1) stabilizes epithelial cell junctions and suppresses TNF-α-induced cytokine production. Biochemical and biophysical research communications 21 31387745
2018 PDE4 and mAKAPβ are nodal organizers of β2-ARs nuclear PKA signalling in cardiac myocytes. Cardiovascular research 21 29733383
2017 Inhibition of HUVEC tube formation via suppression of NFκB suggests an anti-angiogenic role for SLURP1 in the transparent cornea. Experimental eye research 21 28803936
2016 Ibrutinib synergizes with MDM-2 inhibitors in promoting cytotoxicity in B chronic lymphocytic leukemia. Oncotarget 21 27661115
2018 Modulation of HIV replication in monocyte derived macrophages (MDM) by steroid hormones. PloS one 20 29373606
1999 DNA sequence and functional analysis of homologous ARS elements of Saccharomyces cerevisiae and S. carlsbergensis. Genetics 20 10388814
1994 Elevated levels of MDM-2 and p53 expression are associated with high grade non-Hodgkin's lymphomas. Cancer letters 20 7982210
2017 Synergy between Prkdc and Trp53 regulates stem cell proliferation and GI-ARS after irradiation. Cell death and differentiation 19 28686579
2017 Interaction of Synthetic Human SLURP-1 with the Nicotinic Acetylcholine Receptors. Scientific reports 19 29192197

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