Affinage

CTSC

Dipeptidyl peptidase 1 · UniProt P53634

Round 2 corrected
Length
463 aa
Mass
51.9 kDa
Annotated
2026-04-28
130 papers in source corpus 17 papers cited in narrative 16 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CTSC (cathepsin C / dipeptidyl peptidase 1) is a lysosomal cysteine protease that functions as a tetramer whose unique exclusion domain restricts catalysis to the sequential removal of N-terminal dipeptides from polypeptide substrates (PMID:11726493). CTSC is the obligate activator of granule serine proteases—neutrophil elastase, cathepsin G, proteinase 3, and granzymes—by cleaving their two-residue activation peptides; its proenzyme is itself processed by cathepsin L, while endogenous inhibitors (cystatins) and the microRNA miR-23a regulate its activity post-translationally and post-transcriptionally (PMID:8428921, PMID:11327826, PMID:24440757). Loss-of-function mutations in CTSC cause the allelic Mendelian disorders Papillon-Lefèvre syndrome and Haim-Munk syndrome, characterized by palmoplantar keratosis, severe periodontitis, and impaired neutrophil serine protease activity and NET formation (PMID:10581027, PMID:10662807, PMID:34932608). In cancer, tumor-secreted CTSC activates neutrophil PR3 to drive an IL-1β–NF-κB inflammatory cascade and NET-dependent degradation of thrombospondin-1, promoting metastatic colonization, a pathway pharmacologically targetable by DPP-1 inhibitors such as brensocatib (PMID:33450198, PMID:32897034).

Mechanistic history

Synthesis pass · year-by-year structured walk · 8 steps
  1. 1993 High

    Establishing that CTSC is the enzyme responsible for converting pro-forms of granule serine proteases to their active forms resolved how immune effector cells generate mature cathepsin G, granzymes, and related proteases.

    Evidence Pharmacological DPPI inhibition in CD8+ T cells, LAK cells, mast cells, and myeloid lines with pulse-chase labeling showing pro-cathepsin G accumulation

    PMID:8428921

    Open questions at the time
    • Structural basis of dipeptide specificity was unknown
    • Whether CTSC was essential for all granule serine proteases in all immune lineages was untested genetically
  2. 1997 High

    Characterization of the CTSC gene structure and chromosomal location provided the molecular framework for subsequent disease-gene mapping and showed that CTSC expression is transcriptionally regulated by immune signals such as IL-2.

    Evidence Genomic cloning, FISH mapping to 11q14, Northern blot tissue profiling, and IL-2 stimulation of lymphocytes

    PMID:9092576

    Open questions at the time
    • Promoter elements and transcription factors driving tissue-specific expression were not defined
    • Whether IL-2-induced upregulation has functional consequences for serine protease activation was not tested
  3. 1999 High

    Identification of CTSC loss-of-function mutations as the cause of Papillon-Lefèvre syndrome, and subsequently Haim-Munk syndrome, proved that CTSC is essential for normal skin and periodontal homeostasis in humans and that the two syndromes are allelic.

    Evidence Homozygosity mapping, CTSC sequencing in affected families, enzymatic activity assays in patient leukocytes; allelic mutations at the same codon causing PLS vs. HMS

    PMID:10581027 PMID:10593994 PMID:10662807

    Open questions at the time
    • How CTSC deficiency leads specifically to periodontal destruction and keratosis remained mechanistically unclear
    • Modifier genes explaining phenotypic variability between allelic disorders were not identified
  4. 2001 High

    The crystal structure explained how the exclusion domain converts the papain-fold endopeptidase into a strict dipeptidyl aminopeptidase by blocking internal polypeptide access, and showed that disease mutations disrupt this fold; concurrently, in vitro reconstitution demonstrated that cathepsin L is the physiological activator of pro-CTSC.

    Evidence X-ray crystallography of human CTSC tetramer with disease mutation mapping; baculovirus expression of pro-DPPI with in vitro activation by cathepsin L and kinetic inhibition by cystatins

    PMID:11327826 PMID:11726493

    Open questions at the time
    • Dynamics of tetramer assembly in vivo and whether monomeric/dimeric intermediates are functional were not addressed
    • In vivo confirmation that cathepsin L is the predominant activator in specific cell types was lacking
  5. 2004 High

    Analysis of PLS patient immune cells revealed that CTSC dependence for serine protease activation is cell-type-specific: neutrophil cathepsin G and elastase are severely affected, whereas cytotoxic lymphocyte granzymes retain significant activity, resolving an apparent paradox of selective immunodeficiency.

    Evidence Enzymatic activity assays and bactericidal/cytotoxicity functional assays in primary neutrophils and LAK cells from PLS patients

    PMID:15585850

    Open questions at the time
    • Alternative activation pathways for granzymes in lymphocytes were not identified
    • Whether residual granzyme activity is sufficient for all cytotoxic lymphocyte functions in vivo was not determined
  6. 2014 Medium

    Discovery that miR-23a negatively regulates CTSC mRNA introduced a post-transcriptional control layer linking NK cell activation status to granzyme B maturation and cytotoxic potential.

    Evidence miRNA profiling in NK cells, ATRA-mediated miR-23a induction reducing CTSC protein and granzyme B activity, in vivo mouse cytotoxicity model

    PMID:24440757

    Open questions at the time
    • Direct miR-23a binding site validation (e.g., luciferase reporter with mutation) was not shown
    • Relevance of this regulatory axis in neutrophils or other CTSC-dependent cell types was not tested
  7. 2020 High

    A phase 2 clinical trial demonstrated that pharmacological inhibition of CTSC (brensocatib) reduces neutrophil elastase activity in vivo in humans and improves clinical outcomes in bronchiectasis, validating the CTSC–serine protease axis as a therapeutic target.

    Evidence Randomized double-blind placebo-controlled trial measuring sputum neutrophil elastase activity as pharmacodynamic endpoint

    PMID:32897034

    Open questions at the time
    • Long-term immunological consequences of sustained CTSC inhibition in humans were not assessed
    • Whether brensocatib affects granzyme-dependent immunity was not evaluated
  8. 2021 High

    Two advances clarified CTSC's roles in neutrophil biology and cancer: CTSC-deficient neutrophils were shown to have a selective defect in NET formation, and tumor-secreted CTSC was found to promote metastasis via a PR3–IL-1β–NF-κB cascade driving neutrophil recruitment and NET-mediated thrombospondin-1 degradation.

    Evidence PLS patient neutrophil functional profiling showing selective NET impairment; mouse metastasis models with genetic/pharmacological CTSC inhibition, enzymatic reconstitution of CTSC–PR3 activation, NET quantification

    PMID:33450198 PMID:34932608

    Open questions at the time
    • Whether tumor-secreted CTSC activates serine proteases beyond PR3 in the tumor microenvironment is unknown
    • The mechanism by which CTSC is secreted by tumor cells rather than retained in lysosomes was not elucidated

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis of CTSC tetramer assembly dynamics in vivo, the identity of alternative granzyme-activating proteases in lymphocytes, and the long-term immunological safety profile of chronic CTSC inhibition.
  • No in vivo evidence identifying the protease(s) that activate granzymes independently of CTSC
  • No structural data on conformational changes during CTSC proenzyme processing in a cellular context
  • Mechanism of CTSC secretion by tumor cells into the extracellular space is undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 7 GO:0016787 hydrolase activity 4
Localization
GO:0005764 lysosome 3 GO:0005576 extracellular region 1
Pathway
R-HSA-168256 Immune System 5 R-HSA-1643685 Disease 4 R-HSA-392499 Metabolism of proteins 3 GO:0005576 extracellular region 1
Partners
CTSGCTSLELANEGZMBPRTN3

Evidence

Reading pass · 16 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 Crystal structure of human dipeptidyl peptidase I (cathepsin C/CTSC) revealed that an exclusion domain transforms the papain-like endopeptidase framework into a tetrameric enzyme. The four active sites are exposed to solvent in a tetrahedral arrangement, the exclusion domain blocks access of polypeptide chains except at their termini, and Asp1 positions the N-terminal amino group of the substrate, explaining the strict dipeptidyl aminopeptidase specificity. Missense mutations causing Haim-Munk and Papillon-Lefèvre syndromes were mapped to positions that disrupt the fold. X-ray crystallography with functional/structural interpretation; mapping of disease mutations The EMBO journal High 11726493
1993 CTSC (dipeptidyl peptidase I, DPPI) is required for post-translational activation of granule serine proteases in immune cells. Inhibition of DPPI in CD8+ T cells, LAK cells, mast cells, and myeloid cells impaired generation of cathepsin G, granzyme, and other serine protease activities. In U-937 cells, DPPI inhibition caused accumulation of the pro-enzyme form of cathepsin G bearing its N-terminal dipeptide extension, demonstrating that DPPI cleaves the two-residue activation peptide. Pharmacological inhibition of DPPI in cell lines, pulse-chase radiolabeling, immunoblotting for pro- vs. active enzyme forms The Journal of biological chemistry High 8428921
1999 Loss-of-function mutations in CTSC (cathepsin C gene at 11q14) cause Papillon-Lefèvre syndrome (autosomal recessive palmoplantar keratosis and periodontitis). Functional assays in patient leukocytes demonstrated near-total loss of cathepsin C enzymatic activity; obligate carriers showed reduced activity, confirming the causal relationship. Homozygosity mapping, genomic sequencing, functional enzyme activity assay in patient leukocytes Nature genetics High 10581027 10593994
2001 Human pro-DPPI (pro-cathepsin C) expressed in insect cells is a dimer incapable of autoactivation. Cathepsin L efficiently activates pro-DPPI at pH 4.5 via two cleavage pathways: (1) initial cleavage within the pro-region followed by removal of the activation peptide and then separation into heavy/light chains, or (2) separation of the pro-region from the catalytic domain first. Cathepsin S is a less efficient activator; cathepsin B and DPPI itself cannot activate the proenzyme. Cystatin C and stefins A and B inhibit active DPPI with Ki values of 0.5–1.1 nM. Baculovirus expression, affinity purification of active and precursor forms, in vitro activation assays, kinetic inhibition measurements, CD spectroscopy, glycosylation analysis Biochemistry High 11327826
2000 Haim-Munk syndrome (HMS) and Papillon-Lefèvre syndrome (PLS) are allelic disorders caused by mutations in CTSC. A mutation in exon 6 of CTSC (2127A→G, changing a conserved amino acid) segregates with HMS in four nuclear families from the Cochin isolate. A mutation at the same codon (2126C→T) causes classical PLS in a Turkish family, demonstrating that different mutations at the same residue cause phenotypically distinct syndromes. Sequencing of CTSC in affected families, haplotype analysis, co-segregation analysis Journal of medical genetics High 10662807
2004 In humans with Papillon-Lefèvre syndrome (CTSC/DPPI loss-of-function), neutrophil-derived serine proteases (cathepsin G, neutrophil elastase) are severely reduced in activity and stability, confirming DPPI's essential role in their activation. Surprisingly, granzyme activities in cytotoxic lymphocytes (LAK cells) are retained at significant levels, and LAK-mediated cytotoxicity against K562 is normal. Neutrophils from PLS patients do not uniformly fail to kill S. aureus and E. coli, indicating that serine proteases are not the principal bactericidal mechanism. Enzymatic activity assays in primary patient cells (neutrophils, LAK cells), bactericidal assays, immunological functional assays Journal of immunology High 15585850
1997 The human CTSC (dipeptidyl-peptidase I) gene spans ~3.5 kb and consists of two exons and one intron, a genomic organization distinct from other papain-type cysteine proteinases. By FISH, the gene maps to chromosomal region 11q14.1–q14.3. Northern analysis shows highest mRNA expression in lung, kidney, and placenta; high levels in polymorphonuclear leukocytes and alveolar macrophages. IL-2 treatment of lymphocytes significantly increases DPPI mRNA levels, indicating transcriptional regulation. Genomic cloning, FISH chromosomal mapping, Northern blot analysis, IL-2 stimulation experiment The Journal of biological chemistry High 9092576
2014 CTSC mRNA is negatively regulated by miR-23a. In NK cells, activation down-regulates miR-23a, which de-represses CTSC expression, leading to increased cathepsin C protein and granzyme B activity required for cytotoxicity. Treatment with all-trans retinoic acid (ATRA) induces miR-23a expression, decreases CTSC mRNA and protein levels, reduces granzyme B activity, and impairs NK cell cytotoxicity in a mouse model. miRNA/mRNA expression profiling, functional validation with ATRA treatment, in vivo mouse cytotoxicity model, granzyme B activity assay The international journal of biochemistry & cell biology Medium 24440757
2021 Tumor-secreted CTSC promotes breast cancer lung metastasis by enzymatically activating neutrophil membrane-bound proteinase 3 (PR3). Activated PR3 processes IL-1β, which activates NF-κB, upregulating IL-6 and CCL3 for neutrophil recruitment. The CTSC–PR3–IL-1β axis also induces neutrophil ROS production and NET formation; NETs degrade thrombospondin-1 and support metastatic colonization. Pharmacological targeting of CTSC with compound AZD7986 suppresses lung metastasis in a mouse model. In vitro enzymatic activation assays, co-culture experiments, mouse metastasis models (genetic and pharmacological CTSC inhibition), NET quantification, thrombospondin-1 degradation assays, human tumor correlations Cancer cell High 33450198
2020 In a phase 2 clinical trial, brensocatib (INS1007), an oral reversible inhibitor of DPP-1 (cathepsin C/CTSC), reduced sputum neutrophil elastase activity in patients with bronchiectasis and prolonged time to first exacerbation, demonstrating that pharmacological inhibition of CTSC reduces downstream neutrophil serine protease activity in vivo in humans. Randomized double-blind placebo-controlled phase 2 trial; sputum neutrophil elastase activity measured as pharmacodynamic endpoint The New England journal of medicine High 32897034
2002 CTSC mutations in North American PLS families (including novel p.G139R) are associated with dramatically reduced CTSC protease enzyme activity in patient leukocytes, with almost no detectable activity. Biochemical analysis confirmed that mutations altering restriction enzyme sites in conserved regions of CTSC abolish enzymatic function. CTSC gene sequencing, restriction enzyme analysis, direct enzymatic activity measurement in patient leukocytes Human mutation Medium 12112662
2014 Mutations in the CTSC gene cluster predominantly in exons 5–7, which encode the heavy chain of cathepsin C. This region is implicated in tetramerization, suggesting that tetramer formation is important for CTSC enzymatic activity. Genotype–phenotype analysis showed that the same CTSC mutation can produce different phenotypic severity, implicating modifier genes or environmental factors outside CTSC. Mutational database analysis, genotype-phenotype correlation across 75 published mutations Molecular genetics & genomic medicine Low 24936511
2021 In a PLS patient with a 503A>G substitution in CTSC exon 4 (p.Tyr168Cys), neutrophil lysates lacked CTSC protein and showed no CTSC or neutrophil serine protease (NSP) activity. Neutrophil counts, morphology, priming, chemotaxis, radical production, and apoptosis regulation were normal, but NET formation upon PMA stimulation was severely depressed, identifying NSP-dependent NET formation as a specific functional deficit in CTSC-deficient neutrophils. Patient neutrophil functional assays: enzyme activity, chemotaxis, oxidative burst, NET quantification, apoptosis; comparison with another PLS mutation and healthy controls PloS one Medium 34932608
2024 Novel indolinone-based CTSC inhibitor B22 was shown to inhibit CTSC enzymatic activity by binding to the S2 pocket and S1 site of cathepsin C. B22 further inhibits downstream neutrophil serine protease activity and exerts anti-inflammatory effects by modulating cytokine levels in inflammatory bowel disease models in vitro and in vivo. In vitro CTSC activity assay, molecular docking, in vivo IBD mouse model, cytokine measurement European journal of medicinal chemistry Medium 39383651
2022 Fish CTSC (TroCTSC from Trachinotus ovatus) has three conserved catalytic residues (Cys251, His397, Asn419); mutation of any of these dramatically reduces proteolytic activity. Recombinant TroCTSC has optimal hydrolase activity at 40°C and pH 5.5, is promoted by Zn2+ and Ca2+ but inhibited by Fe2+ and Cu2+. TroCTSC localizes to the cytoplasm and partially co-localizes with lysosomes; after V. harveyi stimulation it translocates to the nucleus. Overexpression enhances bacterial clearance and pro-inflammatory cytokine expression; knockdown reduces antibacterial capacity. Site-directed mutagenesis of catalytic residues, recombinant protein activity assay, immunofluorescence/co-localization, in vivo overexpression/knockdown in goldfish Fish & shellfish immunology Medium 35952999
2020 Praeruptorin B reduces migration and invasion of renal carcinoma cells by suppressing the EGFR–MEK–ERK signaling pathway, which leads to downregulation of CTSC mRNA and protein expression. EGF-induced upregulation of CTSC was blocked by praeruptorin B, placing CTSC downstream of EGFR–MEK–ERK signaling in the regulation of tumor cell invasiveness. Cell migration/invasion assays, Western blot for CTSC and signaling proteins, EGF stimulation and praeruptorin B inhibition experiments International journal of molecular sciences Medium 32331211

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
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2015 A human interactome in three quantitative dimensions organized by stoichiometries and abundances. Cell 1015 26496610
2000 DNA cloning using in vitro site-specific recombination. Genome research 815 11076863
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2012 A census of human soluble protein complexes. Cell 689 22939629
2011 Sparse PLS discriminant analysis: biologically relevant feature selection and graphical displays for multiclass problems. BMC bioinformatics 660 21693065
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
2021 Cathepsin C promotes breast cancer lung metastasis by modulating neutrophil infiltration and neutrophil extracellular trap formation. Cancer cell 508 33450198
1994 Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides. Gene 492 8125298
1999 Loss-of-function mutations in the cathepsin C gene result in periodontal disease and palmoplantar keratosis. Nature genetics 365 10581027
2020 Phase 2 Trial of the DPP-1 Inhibitor Brensocatib in Bronchiectasis. The New England journal of medicine 282 32897034
2012 A high-throughput approach for measuring temporal changes in the interactome. Nature methods 273 22863883
2004 Transcriptome characterization elucidates signaling networks that control human ES cell growth and differentiation. Nature biotechnology 266 15146197
2003 Prediction of clinical outcome with microarray data: a partial least squares discriminant analysis (PLS-DA) approach. Human genetics 249 12607117
2009 Proteomic analysis of human parotid gland exosomes by multidimensional protein identification technology (MudPIT). Journal of proteome research 237 19199708
2001 Structure of human dipeptidyl peptidase I (cathepsin C): exclusion domain added to an endopeptidase framework creates the machine for activation of granular serine proteases. The EMBO journal 217 11726493
1999 Mutations of the cathepsin C gene are responsible for Papillon-Lefèvre syndrome. Journal of medical genetics 213 10593994
1993 Generation of active myeloid and lymphoid granule serine proteases requires processing by the granule thiol protease dipeptidyl peptidase I. The Journal of biological chemistry 180 8428921
2004 Papillon-Lefèvre syndrome: correlating the molecular, cellular, and clinical consequences of cathepsin C/dipeptidyl peptidase I deficiency in humans. Journal of immunology (Baltimore, Md. : 1950) 164 15585850
2001 Toward a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs. Genome research 151 11230166
2000 Haim-Munk syndrome and Papillon-Lefèvre syndrome are allelic mutations in cathepsin C. Journal of medical genetics 150 10662807
2000 Molecular cloning and characterization of Pals, proteins associated with mLin-7. The Journal of biological chemistry 147 10753959
2018 Identification of phagocytosis regulators using magnetic genome-wide CRISPR screens. Nature genetics 146 30397336
2001 Human recombinant pro-dipeptidyl peptidase I (cathepsin C) can be activated by cathepsins L and S but not by autocatalytic processing. Biochemistry 142 11327826
2016 FERONIA and Her Pals: Functions and Mechanisms. Plant physiology 139 27342308
2013 In-depth proteomic analyses of exosomes isolated from expressed prostatic secretions in urine. Proteomics 138 23533145
1997 Human dipeptidyl-peptidase I. Gene characterization, localization, and expression. The Journal of biological chemistry 131 9092576
2013 Proteomic analysis of podocyte exosome-enriched fraction from normal human urine. Journal of proteomics 126 23376485
2015 Genome-wide Association Studies Identify Genetic Loci Associated With Albuminuria in Diabetes. Diabetes 125 26631737
2004 A protein interaction framework for human mRNA degradation. Genome research 123 15231747
2000 Statistical analysis of the 5' untranslated region of human mRNA using "Oligo-Capped" cDNA libraries. Genomics 121 10756096
1998 Isolation and characterization of the Saccharomyces cerevisiae DPP1 gene encoding diacylglycerol pyrophosphate phosphatase. The Journal of biological chemistry 113 9452443
1999 The LPP1 and DPP1 gene products account for most of the isoprenoid phosphate phosphatase activities in Saccharomyces cerevisiae. The Journal of biological chemistry 112 10329682
2011 A whole genome screen for HIV restriction factors. Retrovirology 111 22082156
2021 Systematically defining selective autophagy receptor-specific cargo using autophagosome content profiling. Molecular cell 105 33545068
1998 Theoretical Justification of Wavelength Selection in PLS Calibration:  Development of a New Algorithm. Analytical chemistry 102 21644597
1989 Splenic outer periarterial lymphoid sheath (PALS): an immunoproliferative microenvironment constituted by antigen-laden marginal metallophils and ED2-positive macrophages in the rat. Cell and tissue research 88 2790931
2017 MORF9 increases the RNA-binding activity of PLS-type pentatricopeptide repeat protein in plastid RNA editing. Nature plants 84 28394309
2021 Lipidomics study of plasma from patients suggest that ALS and PLS are part of a continuum of motor neuron disorders. Scientific reports 55 34193885
2014 Liaison alcaline: Pals entice non-endosomal ESCRTs to the plasma membrane for pH signaling. Current opinion in microbiology 54 25460796
2001 Prediction of drug transport processes using simple parameters and PLS statistics. The use of ACD/logP and ACD/ChemSketch descriptors. European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences 53 11113652
2001 Regulation of the Saccharomyces cerevisiae DPP1-encoded diacylglycerol pyrophosphate phosphatase by zinc. The Journal of biological chemistry 52 11139591
2013 Structure of a PLS-class pentatricopeptide repeat protein provides insights into mechanism of RNA recognition. The Journal of biological chemistry 51 24047899
2014 CTSC and Papillon-Lefèvre syndrome: detection of recurrent mutations in Hungarian patients, a review of published variants and database update. Molecular genetics & genomic medicine 49 24936511
2016 A PPR protein in the PLS subfamily stabilizes the 5'-end of processed rpl16 mRNAs in maize chloroplasts. Nucleic acids research 46 27095196
2002 PALS db: Putative Alternative Splicing database. Nucleic acids research 43 11752289
2003 PLS-ANN based classification model for oral submucous fibrosis and oral carcinogenesis. Lasers in surgery and medicine 40 12696101
2016 Gene regulatory network inference using PLS-based methods. BMC bioinformatics 39 28031031
2001 Theoretical calculation and prediction of drug transport processes using simple parameters and partial least squares projections to latent structures (PLS) statistics. The use of electrotopological state indices. Journal of pharmaceutical sciences 39 11536212
2014 Deviance residuals-based sparse PLS and sparse kernel PLS regression for censored data. Bioinformatics (Oxford, England) 38 25286920
2021 Precise Diabetic Wound Therapy: PLS Nanospheres Eliminate Senescent Cells via DPP4 Targeting and PARP1 Activation. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 37 34738744
2011 Modeling microRNA-mRNA interactions using PLS regression in human colon cancer. BMC medical genomics 37 21595958
2014 All-trans retinoic acid (ATRA) induces miR-23a expression, decreases CTSC expression and granzyme B activity leading to impaired NK cell cytotoxicity. The international journal of biochemistry & cell biology 36 24440757
2002 Biochemical and mutational analyses of the cathepsin c gene (CTSC) in three North American families with Papillon Lefèvre syndrome. Human mutation 36 12112662
2013 Interaction of PLS and PIN and hormonal crosstalk in Arabidopsis root development. Frontiers in plant science 35 23577016
2019 Comprehensive Prediction of Target RNA Editing Sites for PLS-Class PPR Proteins in Arabidopsis thaliana. Plant & cell physiology 33 30605550
2003 The comparative molecular surface analysis (CoMSA) with modified uniformative variable elimination-PLS (UVE-PLS) method: application to the steroids binding the aromatase enzyme. Journal of chemical information and computer sciences 33 12653535
2011 QSAR models for CXCR2 receptor antagonists based on the genetic algorithm for data preprocessing prior to application of the PLS linear regression method and design of the new compounds using in silico virtual screening. Molecules (Basel, Switzerland) 32 21358586
2008 Determination of the secondary structure of proteins in different environments by FTIR-ATR spectroscopy and PLS regression. Biopolymers 31 18488986
2003 Vacuole membrane topography of the DPP1-encoded diacylglycerol pyrophosphate phosphatase catalytic site from Saccharomyces cerevisiae. The Journal of biological chemistry 31 14630917
2022 Relative contributions of different sources to DOM in Erhai Lake as revealed by PLS-PM. Chemosphere 29 35364075
2017 The Plasmin-Sensitive Protein Pls in Methicillin-Resistant Staphylococcus aureus (MRSA) Is a Glycoprotein. PLoS pathogens 28 28081265
2013 The multi-PDZ domain protein-1 (MUPP-1) expression regulates cellular levels of the PALS-1/PATJ polarity complex. Experimental cell research 28 23880463
2012 A comparison of partial least squares (PLS) and sparse PLS regressions in genomic selection in French dairy cattle. Journal of dairy science 26 22459857
1999 Simultaneous determination of paracetamol, caffeine and acetylsalicylic acid by means of a FI ultraviolet pls multioptosensing device. Journal of pharmaceutical and biomedical analysis 26 10703966
2024 Optimizing feature selection with gradient boosting machines in PLS regression for predicting moisture and protein in multi-country corn kernels via NIR spectroscopy. Food chemistry 25 38876073
2018 Fast discrimination of bacteria using a filter paper-based SERS platform and PLS-DA with uncertainty estimation. Analytical and bioanalytical chemistry 25 30450510
2005 The surface protein Pls of methicillin-resistant Staphylococcus aureus is a virulence factor in septic arthritis. Infection and immunity 25 15845485
2023 Multiple pals gene modules control a balance between immunity and development in Caenorhabditis elegans. PLoS pathogens 24 37463170
2017 Comparison of FTIR-ATR and Raman spectroscopy in determination of VLDL triglycerides in blood serum with PLS regression. Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy 24 28454077
2007 Flow-batch technique for the simultaneous enzymatic determination of levodopa and carbidopa in pharmaceuticals using PLS and successive projections algorithm. Talanta 24 18585168
2003 Regulation of the yeast DPP1-encoded diacylglycerol pyrophosphate phosphatase by transcription factor Gis1p. The Journal of biological chemistry 24 12799368
2003 A quantitative structure-antifungal activity relationship study of oxygenated aromatic essential oil compounds using data structuring and PLS regression analysis. Journal of molecular modeling 24 14689256
2002 New molecular surface-based 3D-QSAR method using Kohonen neural network and 3-way PLS. Computers & chemistry 24 12385475
2006 The application of a 3D-QSAR (autoMEP/PLS) approach as an efficient pharmacodynamic-driven filtering method for small-sized virtual library: application to a lead optimization of a human A3 adenosine receptor antagonist. Bioorganic & medicinal chemistry 22 16564691
2006 Hierarchical PLS modeling for predicting the binding of a comprehensive set of structurally diverse protein-ligand complexes. Journal of chemical information and modeling 22 16711735
2005 Development of a PLS based method for determination of the quality of beers by use of NIR: spectral ranges and sample-introduction considerations. Analytical and bioanalytical chemistry 22 15997377
2022 A pals-25 gain-of-function allele triggers systemic resistance against natural pathogens of C. elegans. PLoS genetics 21 36191002
2000 Regulation of the DPP1-encoded diacylglycerol pyrophosphate (DGPP) phosphatase by inositol and growth phase. Inhibition of DGPP phosphatase activity by CDP-diacylglyceron and activation of phosphatidylserine synthase activity by DGPP. The Journal of biological chemistry 21 11016943
2023 Determination of corn protein content using near-infrared spectroscopy combined with A-CARS-PLS. Food chemistry: X 20 37096170
2008 Selecting subsets of newly extracted features from PCA and PLS in microarray data analysis. BMC genomics 20 18831790
2012 Preliminary antifungal and cytotoxic evaluation of synthetic cycloalkyl[b]thiophene derivatives with PLS-DA analysis. Acta pharmaceutica (Zagreb, Croatia) 19 22750820
2007 Staphylococcal chromosomal cassette mec type I, spa type, and expression of Pls are determinants of reduced cellular invasiveness of methicillin-resistant Staphylococcus aureus isolates. The Journal of infectious diseases 19 17471438
2020 Praeruptorin B Mitigates the Metastatic Ability of Human Renal Carcinoma Cells through Targeting CTSC and CTSV Expression. International journal of molecular sciences 17 32331211
2010 Gene association networks from microarray data using a regularized estimation of partial correlation based on PLS regression. IEEE/ACM transactions on computational biology and bioinformatics 17 20431145
2007 Novel, customizable scoring functions, parameterized using N-PLS, for structure-based drug discovery. Journal of chemical information and modeling 17 17238252
2022 WAL3 encoding a PLS-type PPR protein regulates chloroplast development in rice. Plant science : an international journal of experimental plant biology 15 35850283
2009 Pals-associated tight junction protein functionally links dopamine and angiotensin II to the regulation of sodium transport in renal epithelial cells. British journal of pharmacology 15 19563532
2016 UPLC-QTOFMS based metabolomics followed by stepwise partial least square-discriminant analysis (PLS-DA) explore the possible relation between the variations in secondary metabolites and the phylogenetic divergences of the genus Panax. Journal of chromatography. B, Analytical technologies in the biomedical and life sciences 14 26807706
2015 Irreversible dual inhibitory mode: the novel Btk inhibitor PLS-123 demonstrates promising anti-tumor activity in human B-cell lymphoma. Oncotarget 14 25944695
2004 The operons, a criterion to compare the reliability of transcriptome analysis tools: ICA is more reliable than ANOVA, PLS and PCA. Computational biology and chemistry 14 15022635
2019 Decision Tree-PLS (DT-PLS) algorithm for the development of process: Specific local prediction models. Biotechnology progress 13 30969466
2015 One mutation, two phenotypes: a single nonsense mutation of the CTSC gene causes two clinically distinct phenotypes. Clinical and experimental dermatology 13 26205983
2007 DFT study on the structure-toxicity relationship of dioxin compounds using PLS analysis. SAR and QSAR in environmental research 13 17654340
2006 Parallel factor analysis combined with PLS regression applied to the on-line monitoring of Pichia pastoris cultures. Analytical and bioanalytical chemistry 13 16538457
2021 Phospholipids (PLs) know-how: exploring and exploiting phospholipase D for its industrial dissemination. Critical reviews in biotechnology 12 33985392
2021 Sparse PLS-Based Method for Overlapping Metabolite Set Enrichment Analysis. Journal of proteome research 12 34002606
2021 The Cognitive Model of Negative Symptoms in Schizophrenia: A Hierarchical Component Model With PLS-SEM. Frontiers in psychiatry 12 34366940
2020 Modelling the vigour of maize seeds submitted to artificial accelerated ageing based on ATR-FTIR data and chemometric tools (PCA, HCA and PLS-DA). Heliyon 12 32140593
2019 A 3D-QSAR Analysis of CDK2 Inhibitors Using FMO Calculations and PLS Regression. Chemical & pharmaceutical bulletin 12 31155560
2015 Robust Ultraviolet-Visible (UV-Vis) Partial Least-Squares (PLS) Models for Tannin Quantification in Red Wine. Journal of agricultural and food chemistry 12 25591104
2014 Aconitum and delphinium diterpenoid alkaloids of local anesthetic activity: comparative QSAR analysis based on GA-MLRA/PLS and optimal descriptors approach. Journal of environmental science and health. Part C, Environmental carcinogenesis & ecotoxicology reviews 12 25226219
2013 Simultaneous measurement of two enzyme activities using infrared spectroscopy: A comparative evaluation of PARAFAC, TUCKER and N-PLS modeling. Analytica chimica acta 12 23870404
2013 Complementary PLS and KNN algorithms for improved 3D-QSDAR consensus modeling of AhR binding. Journal of cheminformatics 12 24257141
2007 Potential of front face fluorescence associated to PLS regression to predict nutritional parameters in heat treated infant formula models. Analytica chimica acta 12 18082646
2021 Liver proteome profiling in dairy cows during the transition from gestation to lactation: Effects of supplementation with essential fatty acids and conjugated linoleic acids as explored by PLS-DA. Journal of proteomics 11 34839038
2013 A novel seven-base deletion of the CTSC gene identified in a Hungarian family with Papillon-Lefèvre syndrome. Archives of dermatological research 11 23397598
2013 A nonlinearized multivariate dominant factor-based partial least squares (PLS) model for coal analysis by using laser-induced breakdown spectroscopy. Applied spectroscopy 11 23452493
2010 Development and validation of a simple cell-based fluorescence assay for dipeptidyl peptidase 1 (DPP1) activity. Journal of biomolecular screening 11 21088147
2003 Multi-way PLS modeling of structure-activity data by incorporating electrostatic and lipophilic potentials on molecular surface. Computational biology and chemistry 11 12927112
2022 Cathepsin C (CTSC) contributes to the antibacterial immunity in golden pompano (Trachinotus ovatus). Fish & shellfish immunology 10 35952999
2019 Exome sequencing identifies a novel missense variant in CTSC causing nonsyndromic aggressive periodontitis. Journal of human genetics 10 31068678
2014 Docking and PLS studies on a set of thiophenes RNA polymerase inhibitors against Staphylococcus aureus. Current topics in medicinal chemistry 10 24236725
2011 PLS-DA - Docking Optimized Combined Energetic Terms (PLSDA-DOCET) protocol: a brief evaluation. Journal of chemical information and modeling 10 22066983
2023 Staphylococcal Periscope proteins Aap, SasG, and Pls project noncanonical legume-like lectin adhesin domains from the bacterial surface. The Journal of biological chemistry 9 36702253
2021 A rare CTSC mutation in Papillon-Lefèvre Syndrome results in abolished serine protease activity and reduced NET formation but otherwise normal neutrophil function. PloS one 9 34932608
2007 A PLS-based extractive spectrophotometric method for simultaneous determination of carbamazepine and carbamazepine-10,11-epoxide in plasma and comparison with HPLC. Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy 9 17307386
2006 [The PLS calibration model optimization and determination of rice protein content by near-infrared reflectance spectroscopy]. Guang pu xue yu guang pu fen xi = Guang pu 9 16883848
2004 Retrospective statistical analysis of lyophilized protein formulations of progenipoietin using PLS: determination of the critical parameters for long-term storage stability. Journal of pharmaceutical sciences 9 15349970
2024 The Prostate Cancer Active Lifestyle Study (PALS): A randomized controlled trial of diet and exercise in overweight and obese men on active surveillance. Cancer 8 38353455
2024 Biomarkers in cardiogenic shock: old pals, new friends. Annals of intensive care 8 39414666
2022 Poor sleep quality is associated with fatigue and depression in early Parkinson's disease: A longitudinal study in the PALS cohort. Frontiers in neurology 8 36119701
2022 Growth, physiological, and temperature characteristics in chinese cabbage pakchoi as affected by Cd- stressed conditions and identifying its main controlling factors using PLS model. BMC plant biology 8 36476235
2012 Improving stability and understandability of genotype-phenotype mapping in Saccharomyces using regularized variable selection in L-PLS regression. BMC bioinformatics 8 23216988
2007 Detection of an intragenic deletion expands the spectrum of CTSC mutations in Papillon-Lefèvre syndrome. The Journal of investigative dermatology 8 17943190
2024 Rare variant analyses validate known ALS genes in a multi-ethnic population and identifies ANTXR2 as a candidate in PLS. BMC genomics 7 38951798
2024 Identification of novel indolinone derivatives as CTSC inhibitors to treat inflammatory bowel disease by modulating inflammatory factors. European journal of medicinal chemistry 7 39383651
2008 PaLS: filtering common literature, biological terms and pathway information. Nucleic acids research 7 18467422