Affinage

DPP9

Dipeptidyl peptidase 9 · UniProt Q86TI2

Length
863 aa
Mass
98.3 kDa
Annotated
2026-04-28
48 papers in source corpus 23 papers cited in narrative 23 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

DPP9 is a cytosolic serine dipeptidyl peptidase that cleaves N-terminal Xaa-Pro dipeptides from substrates including Syk, AK2, and BRCA2, thereby targeting them for proteasomal degradation via the N-degron pathway, and additionally functions as a non-catalytic scaffold that modulates inflammasome activation, redox homeostasis, and ubiquitin signaling (PMID:27614019, PMID:32815200, PMID:37230592). Cryo-EM structures reveal that DPP9 forms an inhibitory ternary complex with full-length NLRP1 and the NLRP1 C-terminal fragment—whose N-terminus inserts into the DPP9 active site—and both catalytic activity and scaffolding binding are required to suppress NLRP1 and CARD8 inflammasome activation; disruption of this complex by pharmacological inhibitors or viral proteins triggers pyroptosis (PMID:33731932, PMID:33731929, PMID:30291141, PMID:40608794). Independent of its peptidase activity, DPP9 competes with NRF2 for KEAP1 binding via a conserved ESGE motif, stabilizing NRF2 to drive antioxidant gene expression and suppress ferroptosis, and disrupts the BRISC deubiquitinase complex to enhance IFNAR1-mediated JAK/STAT signaling and PD-L1 expression (PMID:37713596, PMID:39615677, PMID:41826729). De novo loss-of-function DPP9 mutations cause constitutive NLRP1/CARD8 inflammasome activation and severe autoinflammation in humans (PMID:37544411).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 2002 Medium

    Establishing DPP9 as a new member of the DPP IV serine protease family with cytosolic localization resolved its gene family membership and predicted intracellular rather than extracellular substrates.

    Evidence In silico identification, in vitro translation, SDS-PAGE, and northern blot showing ~98 kDa protein lacking transmembrane domains

    PMID:12459266

    Open questions at the time
    • No endogenous substrates identified
    • Catalytic activity not demonstrated against peptide substrates
    • Cellular localization not confirmed by imaging
  2. 2009 High

    Demonstrating that DPP9 is rate-limiting for cytoplasmic proline-containing peptide degradation and influences MHC-I antigen presentation established its first defined cellular function.

    Evidence In vitro cleavage of RU1(34-42) peptide plus siRNA knockdown showing enhanced antigen presentation in intact cells

    PMID:19667070

    Open questions at the time
    • Protein substrates not yet identified
    • In vivo relevance to immune surveillance not tested
  3. 2012 High

    Discovery that SUMO1 binds DPP9 via a non-canonical site on an extended arm near the substrate entry region and stimulates its enzymatic activity revealed the first allosteric regulator of DPP9.

    Evidence Co-IP, mutagenesis of SUMO1-binding arm, in vitro activity assays, and SUMO1 siRNA knockdown reducing cytosolic prolyl-peptidase activity

    PMID:23152501

    Open questions at the time
    • Structural basis of SUMO1-DPP9 interaction not resolved at atomic level
    • Physiological conditions modulating SUMO1-DPP9 interaction unknown
  4. 2016 High

    Linking DPP8/DPP9 inhibition to caspase-1-dependent pyroptosis and gasdermin D cleavage in monocytes identified the inflammasome axis as a major DPP9-regulated pathway, and demonstrating that DPP9 cleaves Syk to generate an N-degron established its role in targeted protein degradation.

    Evidence Val-boroPro treatment of monocytes/macrophages and caspase-1 KO mice for inflammasome; Co-IP, pulse-chase, and mutagenesis for Syk N-terminal processing and Cbl-mediated ubiquitination

    PMID:27614019 PMID:27820798

    Open questions at the time
    • DPP8 vs DPP9 individual contributions to pyroptosis not resolved
    • Inflammasome sensor upstream of caspase-1 not yet identified
    • Full scope of N-degron substrates unknown
  5. 2018 High

    Identifying CARD8 as the sensor mediating DPP8/9 inhibitor-induced pyroptosis in human myeloid cells, and demonstrating DPP9 as a direct binding partner and endogenous inhibitor of both NLRP1 and CARD8 inflammasomes via the FIIND domain, resolved the upstream sensor question and established DPP9 as a dual inflammasome checkpoint.

    Evidence CARD8 KO/knockdown with pharmacological inhibition in myeloid cells; proteomics screen, Co-IP, CRISPR KO, and patient NLRP1 FIIND mutation abrogating DPP9 binding

    PMID:29967349 PMID:30291141

    Open questions at the time
    • Structural basis of DPP9-FIIND interaction not yet resolved
    • Relative contributions of DPP9 catalytic vs scaffolding functions not disentangled
  6. 2018 High

    Knock-in mice expressing catalytically inactive DPP9 (S729A) demonstrated that DPP9 enzymatic activity is essential in vivo for survival of migratory tongue muscle progenitors, establishing a non-redundant developmental role.

    Evidence S729A knock-in mice showing microglossia, increased apoptosis of occipital somite progenitors, suckling defect, and neonatal lethality

    PMID:28887018

    Open questions at the time
    • Substrate(s) responsible for muscle progenitor phenotype not identified
    • Whether inflammasome dysregulation contributes to neonatal lethality not tested
  7. 2020 High

    Identification of AK2 as a DPP9 substrate showed that DPP9-mediated N-terminal processing diverts proteins from mitochondrial import to proteasomal degradation, broadening DPP9's role beyond signaling kinases to organellar protein quality control.

    Evidence siRNA knockdown, proteasome inhibition, pulse-chase, and biochemical fractionation demonstrating DPP9 processing triggers AK2 degradation and prevents cytosolic accumulation

    PMID:32815200

    Open questions at the time
    • Full inventory of DPP9 N-degron substrates still incomplete
    • Whether DPP9 regulates import of other mitochondrial proteins unknown
  8. 2021 High

    Cryo-EM structures of the NLRP1-DPP9 ternary complex revealed the atomic mechanism of inflammasome suppression: the NLRP1 C-terminal fragment N-terminus inserts into the DPP9 active site, and full-length NLRP1 is required to scaffold this interaction, explaining how VbP disrupts the complex to activate inflammasome signaling.

    Evidence Cryo-EM structures (human and rat), biochemical reconstitution, mutagenesis, and functional inflammasome assays

    PMID:33731929 PMID:33731932

    Open questions at the time
    • High-resolution structure of CARD8-DPP9 complex not determined
    • Endogenous signals that shift the NLRP1 CT/full-length ratio in vivo remain elusive
  9. 2023 Medium

    Discovery that DPP9 binds KEAP1 via an ESGE motif to competitively displace NRF2, stabilizing the antioxidant response independently of DPP9 catalytic activity, revealed a major enzyme-independent scaffolding function linking DPP9 to redox homeostasis and chemoresistance.

    Evidence Co-IP with ESGE motif mutagenesis, NRF2 stability and transcription assays, ROS measurement, and ferroptosis/sorafenib resistance assays in ccRCC cells

    PMID:37713596

    Open questions at the time
    • Physiological trigger switching DPP9 between active and KEAP1-bound inactive conformations not defined
    • In vivo validation of DPP9-KEAP1 axis in animal models lacking
    • Whether DPP9-KEAP1 interaction is tissue-specific unknown
  10. 2023 Medium

    A de novo DPP9 mutation (p.Arg252Pro) causing severe autoinflammation in a patient demonstrated that DPP9 loss of function is sufficient to constitutively activate NLRP1 and CARD8 inflammasomes in humans, establishing DPP9 deficiency as a Mendelian autoinflammatory condition.

    Evidence Functional validation in HEK293T cells and patient-derived iPSCs showing protein destabilization and constitutive inflammasome activation

    PMID:37544411

    Open questions at the time
    • Single patient reported; additional patients needed to define genotype-phenotype spectrum
    • Whether partial loss of DPP9 activity confers intermediate inflammatory phenotypes unknown
  11. 2024 Medium

    Reciprocal biochemical analysis showed that KEAP1 preferentially binds inactive/misfolded DPP9, stabilizing this non-native form, while inactive DPP9 in turn blocks KEAP1-NRF2 interaction—establishing a redox-sensitive feedback loop between DPP9 conformational state and antioxidant signaling.

    Evidence Co-IP, DPP9 activity assays under various conditions, NRF2 stability assays; DPP9 KD/OE with ubiquitination and ROS readouts in liver cancer cells

    PMID:39094401 PMID:39615677

    Open questions at the time
    • Identity of the cellular signal driving DPP9 misfolding/inactivation not established
    • Structural basis of KEAP1 recognizing inactive DPP9 not resolved
  12. 2025 Medium

    Demonstration that SFTSV NSs protein activates NLRP1/CARD8 inflammasomes by competing with DPP9 for FIIND binding and promoting DPP9 degradation established viral hijacking of the DPP9 inflammasome checkpoint as a pathogenic mechanism.

    Evidence Primary keratinocyte and macrophage infection, Co-IP, inflammasome activation assays, CARD8 deletion studies

    PMID:40608794

    Open questions at the time
    • Whether other viruses exploit the same DPP9-displacement strategy unknown
    • Structural basis of NSs-FIIND interaction not resolved
  13. 2026 Medium

    Proximity labeling and NanoBRET identified DPP9 as a non-catalytic disruptor of BRISC (BRCC36-ABRO1) and CYLD-SPATA2 deubiquitinase complexes, and functional studies showed DPP9 enhances BRISC-mediated IFNAR1 deubiquitination to drive JAK/STAT-dependent PD-L1 expression, revealing a scaffolding role in immune checkpoint regulation.

    Evidence TurboID proximity labeling, Co-IP, NanoBRET in living cells; IFNAR1 ubiquitination assays, JAK/STAT pathway assays, T cell cytotoxicity assays, and in vivo mouse models with DPP9 inhibitor 1G244

    PMID:41636814 PMID:41826729

    Open questions at the time
    • Direct structural interface between DPP9 and BRISC components not mapped
    • Whether DPP9-BRISC interaction is catalytic-activity-dependent or independent not fully resolved
    • In vivo immunotherapy efficacy of DPP9 inhibition not tested in clinical setting

Open questions

Synthesis pass · forward-looking unresolved questions
  • Major open questions include the complete inventory of physiological DPP9 N-degron substrates, the structural basis of the CARD8-DPP9 complex, the endogenous signals that toggle DPP9 between active and inactive/KEAP1-bound states, and whether DPP9's scaffolding roles in ubiquitin signaling and inflammasome suppression are coordinated or independent pathways.
  • Full substrate repertoire via unbiased proteomics not yet reported
  • CARD8-DPP9 complex structure not determined
  • Physiological trigger for DPP9 conformational switching unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 7 GO:0016787 hydrolase activity 6 GO:0140096 catalytic activity, acting on a protein 5 GO:0060090 molecular adaptor activity 3
Localization
GO:0005829 cytosol 3
Pathway
R-HSA-168256 Immune System 9 R-HSA-162582 Signal Transduction 3 R-HSA-392499 Metabolism of proteins 3 R-HSA-5357801 Programmed Cell Death 3 R-HSA-8953897 Cellular responses to stimuli 3
Partners
ABRO1BRCC3CARD8CBLFLNAKEAP1NLRP1SUMO1
Complex memberships
CARD8-DPP9 complexNLRP1-DPP9 ternary complex

Evidence

Reading pass · 23 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2002 DPP9 was identified as a novel cytosolic serine protease with a catalytic triad (Ser, Asp, His) and a GWSYG motif identical to DPP IV, placing it in the DPP IV gene family. It lacks transmembrane domains and a signal sequence, consistent with cytosolic localization, and in vitro translation produced a ~98 kDa protein. In silico identification, in vitro translation, SDS-PAGE, northern blot Gene Medium 12459266
2009 DPP9 is rate-limiting for degradation of proline-containing peptides in the cytoplasm. DPP9 cleaves the natural substrate RU1(34-42) antigenic peptide in vitro, and DPP9 knockdown in intact cells results in increased antigen presentation of this peptide, demonstrating a role in antigen presentation via peptide turnover. In vitro peptidase assay, siRNA knockdown in intact cells, antigen presentation assay The Journal of biological chemistry High 19667070
2009 Bovine DPP9 purified from testes exists as the short-form isoform, is activated and stabilized by DTT, and loses activity upon alkylation (N-ethylmaleimide, iodoacetamide), indicating dependence on free cysteine residues for enzymatic activity. No evidence of glycosylation was found. Purification, MALDI-TOF/TOF MS, N-terminal sequencing, enzymatic activity assays with chemical modifiers Biochimica et biophysica acta Medium 20026260
2012 DPP9 binds SUMO1 via a novel interaction site (not the canonical SIM motif) involving an extended arm structure flanking the substrate entry site. SUMO1 binding stimulates DPP9 enzymatic activity, and SUMO1 silencing reduces cytosolic prolyl-peptidase activity. Mutants in the SUMO1-binding arm are less catalytically active than wild-type DPP9. Co-IP, mutagenesis, in vitro activity assay, siRNA knockdown The Journal of biological chemistry High 23152501
2016 DPP8 and DPP9 inhibition by Val-boroPro (Talabostat) activates pro-caspase-1 independent of the inflammasome adaptor ASC in monocytes and macrophages. Activated pro-caspase-1 cleaves gasdermin D to induce pyroptosis without efficiently processing itself or IL-1β. Mice lacking caspase-1 do not show immune stimulation after Val-boroPro treatment. Pharmacological inhibition, caspase-1 knockout mice, gasdermin D cleavage assay, cell death assay Nature chemical biology High 27820798
2016 DPP9 cleaves Syk kinase to produce a neo N-terminus with serine at position 1, which destabilizes Syk via the N-end rule pathway. DPP9 interacts with Filamin A, which recruits DPP9 to Syk. DPP9 processing is a prerequisite for Cbl-mediated Syk ubiquitination, and DPP9 inhibition stabilizes Syk and modulates B-cell signaling. Co-IP, pulse-chase experiments, mutagenesis, siRNA knockdown, N-end rule pathway assays eLife High 27614019
2018 DPP8/DPP9 inhibitors induce caspase-1-dependent pyroptosis in human myeloid cells via CARD8. CARD8 mediates DPP8/DPP9 inhibitor-induced pyroptosis in human myeloid cells, and these inhibitors inhibit AML progression in mouse xenograft models. Pharmacological inhibition, CARD8 knockdown/knockout, caspase-1 activity assays, AML mouse models Nature medicine High 29967349
2018 DPP9 is a direct binding partner of NLRP1 and CARD8, interacting via the FIIND (Function to Find Domain). DPP9 acts as an endogenous inhibitor of the NLRP1 inflammasome. Both DPP9 catalytic activity and its scaffolding interaction with the NLRP1 FIIND act synergistically to maintain NLRP1 in its inactive state. A patient-derived NLRP1 FIIND missense mutation that abrogates DPP9 binding causes inflammasome hyperactivation. Proteomics screen, Co-IP, CRISPR/Cas9 knockout, small molecule inhibition, ASC speck formation assay, IL-1β secretion assay The Journal of biological chemistry High 30291141
2018 DPP9 enzyme activity in vivo controls survival of migratory tongue muscle progenitors. Knock-in mice expressing catalytically inactive DPP9 (S729A) display microglossia due to increased apoptosis of occipital somite-derived muscle progenitors, leading to suckling defect and neonatal lethality. Knock-in mouse model (S729A catalytic mutant), histology, apoptosis assays, developmental analysis Developmental biology High 28887018
2018 DPP9 inhibition (by saxagliptin or TC-E5007) in cardiomyocytes impairs CaMKII-phospholamban signaling and PKC activity. Knockdown of DPP9 (but not DPP8) recapitulates these effects, implicating DPP9 specifically in cardiac CaMKII/PKC signaling. Saxagliptin impairs Ca2+ transient relaxation and prolongs action potential duration via DPP9 inhibition. Pharmacological inhibition, siRNA knockdown, CaMKII/PKC activity assays, Ca2+ transient measurements, action potential recordings Frontiers in physiology Medium 30487758
2019 DPP9's catalytic activity, not its binding to CARD8, restrains the CARD8 inflammasome. Wild-type but not catalytically inactive DPP9 rescues CARD8-mediated cell death in DPP9-knockout cells. The DPP9-CARD8 interaction is not disrupted by DPP9 inhibitors, unlike the DPP9-NLRP1 interaction. Activity-based probes, reconstituted inflammasome assays, mass spectrometry proteomics, DPP9 knockout cells, catalytic mutant rescue ACS chemical biology High 31525884
2020 DPP8/DPP9 mediate N-terminal processing of adenylate kinase 2 (AK2), a mitochondrial protein lacking an N-terminal targeting sequence. DPP9-mediated processing of AK2 induces its rapid proteasomal degradation and prevents cytosolic accumulation of enzymatically active AK2, thus regulating the competition between mitochondrial import and proteasomal degradation. siRNA knockdown, proteasome inhibition, biochemical fractionation, pulse-chase analysis, proteomic identification of DPP8/9 substrates The EMBO journal High 32815200
2021 Cryo-EM structures of the human NLRP1-DPP9 complex reveal a ternary complex comprising DPP9, full-length NLRP1, and the NLRP1 C-terminal fragment (CT). The N-terminus of the NLRP1 CT inserts into the DPP9 active site. Val-boroPro (VbP) disrupts this interaction, weakening the NLRP1-DPP9 complex and accelerating degradation of the NLRP1 N-terminal fragment to activate the inflammasome. Full-length NLRP1 is required for NLRP1 CT binding to DPP9, suggesting inflammasome activation is regulated by the ratio of NLRP1 CT to full-length NLRP1. Cryo-EM structure determination, biochemical binding assays, ectopic expression rescue experiments, VbP inhibitor studies Nature High 33731932
2021 Structural and biochemical analysis of rat NLRP1-DPP9 reveals a 2:1 complex containing one autoinhibited full-length NLRP1 and one active UPA-CARD fragment of NLRP1 bound to DPP9. The NLRP1 ZU5 domain is required for both autoinhibition and 2:1 complex assembly. Complex formation prevents UPA-mediated higher-order oligomerization and strengthens ZU5-mediated autoinhibition. Both NLRP1 binding and enzymatic activity of DPP9 are required to suppress NLRP1 inflammasome in human cells. Cryo-EM, X-ray crystallography, biochemical reconstitution, mutagenesis, functional inflammasome assays Nature High 33731929
2022 The NLRP1 disease variant M1184V stabilizes the FIIND domain in a monomeric conformation, promotes autoproteolysis, enhances DPP9 binding (as shown by surface plasmon resonance and immunoprecipitation), and leads to improved formation of an autoinhibited complex with DPP9. Size-exclusion chromatography, surface plasmon resonance, molecular dynamics simulation, immunoprecipitation, activity assays The Journal of biological chemistry Medium 36309085
2023 DPP9 binds to KEAP1 via a conserved ESGE motif and disrupts KEAP1-NRF2 binding by competing with NRF2 for KEAP1 in an enzyme-independent manner. DPP9 overexpression stabilizes NRF2, drives NRF2-dependent transcription, decreases cellular ROS, suppresses ferroptosis, and induces sorafenib resistance in ccRCC cells via upregulation of the NRF2 target SLC7A11. Protein affinity purification, Co-IP, mutagenesis (ESGE motif), cell viability assays, ROS measurement, ferroptosis assays Cancer research Medium 37713596
2023 DPP9 and DPP8 function as amino-dipeptidyl peptidases that remove N-terminal Xaa-Pro dipeptides. Confirmed substrates include Syk, AK2, and BRCA2; N-terminal processing of these proteins by DPP9 triggers their rapid proteasomal degradation via the N-degron pathway. Enzymatic assays, substrate identification, proteomics (review/methods chapter with original data on purification) Methods in enzymology Medium 37230592
2023 A de novo DPP9 mutation (p.Arg252Pro) destabilizes the DPP9 protein and abolishes its ability to restrain NLRP1 and CARD8 inflammasomes in HEK293T cells and patient-derived iPSCs, resulting in constitutive inflammasome activation and severe autoinflammation, demonstrating that DPP9 protein stability is required for inflammasome suppression. Heterologous expression in HEK293T, patient-derived iPSCs, inflammasome activation assays, protein stability assessment The Journal of allergy and clinical immunology Medium 37544411
2024 KEAP1 binds DPP9 in an inactive (non-native) conformation and stabilizes this misfolded state. Reciprocally, this inactive form of DPP9 inhibits KEAP1-mediated NRF2 degradation by preventing KEAP1-NRF2 interaction, thereby inducing an antioxidant response. This reveals an endogenous mechanism for DPP9 inhibition linked to the intracellular redox state. Co-IP, biochemical binding assays, NRF2 stability assays, DPP9 enzymatic activity assays under various conditions The Journal of biological chemistry Medium 39615677
2024 DPP9 inhibition in liver cancer cells reduces NRF2 stability by releasing KEAP1 from DPP9 binding, thereby increasing KEAP1-mediated NRF2 ubiquitination. DPP9 overexpression up-regulates NQO1 via NRF2 and inhibits intracellular ROS, promoting chemoresistance; NQO1 inhibition by dicoumarol reverses this. siRNA knockdown, overexpression, ubiquitination assay, ROS measurement, cell viability assay with chemotherapy drugs Redox biology Medium 39094401
2025 SFTSV non-structural protein (NSs) activates NLRP1 and CARD8 inflammasomes by disrupting the DPP9-mediated inhibitory ternary complex: NSs interacts with NLRP1/CARD8 FIIND domains (competing with DPP8/9 binding) and promotes degradation of DPP8/DPP9, releasing activated C-terminal fragments. Primary keratinocyte and macrophage infection assays, Co-IP, inflammasome activation assays, CARD8 deletion studies PLoS pathogens Medium 40608794
2026 Proximity labeling (TurboID) of DPP9 in DPP9-knockout cells identified novel DPP9 interactors including DPP8, the E3 ligase CBL, the deubiquitinase complex CYLD-SPATA2, and the BRISC complex (BRCC36/BRCC3 and ABRO1/ABRAXAS2). NanoBRET assays demonstrated that DPP9 disrupts BRCC36-ABRO1 binding and CYLD-SPATA2 binding, revealing non-catalytic scaffolding functions of DPP9 in the ubiquitin system. TurboID proximity labeling, mass spectrometry, Co-IP validation, NanoBRET assays in living cells Cellular and molecular life sciences Medium 41636814
2026 DPP9 disrupts the BRISC-SHMT2 complex, enhancing BRISC-mediated deubiquitination of IFNAR1, which activates JAK/STAT signaling and drives PD-L1 transcription in ccRCC. DPP9 inhibition with 1G244 reverses this by reducing DPP9-SHMT2 interaction, promoting IFNAR1 ubiquitination and degradation, and restoring T cell cytotoxicity. Co-IP, pharmacological inhibition (1G244), IFNAR1 ubiquitination assays, JAK/STAT pathway assays, T cell cytotoxicity assays, in vivo mouse models Cell death and differentiation Medium 41826729

Source papers

Stage 0 corpus · 48 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2018 DPP8/DPP9 inhibitor-induced pyroptosis for treatment of acute myeloid leukemia. Nature medicine 298 29967349
2016 DPP8 and DPP9 inhibition induces pro-caspase-1-dependent monocyte and macrophage pyroptosis. Nature chemical biology 241 27820798
2018 Human DPP9 represses NLRP1 inflammasome and protects against autoinflammatory diseases via both peptidase activity and FIIND domain binding. The Journal of biological chemistry 186 30291141
2021 DPP9 sequesters the C terminus of NLRP1 to repress inflammasome activation. Nature 163 33731932
2021 Structural and biochemical mechanisms of NLRP1 inhibition by DPP9. Nature 123 33731929
2002 Identification and characterization of human DPP9, a novel homologue of dipeptidyl peptidase IV. Gene 119 12459266
2009 The cytoplasmic peptidase DPP9 is rate-limiting for degradation of proline-containing peptides. The Journal of biological chemistry 92 19667070
2023 DPP9 Stabilizes NRF2 to Suppress Ferroptosis and Induce Sorafenib Resistance in Clear Cell Renal Cell Carcinoma. Cancer research 86 37713596
2012 A novel SUMO1-specific interacting motif in dipeptidyl peptidase 9 (DPP9) that is important for enzymatic regulation. The Journal of biological chemistry 56 23152501
2019 DPP9's Enzymatic Activity and Not Its Binding to CARD8 Inhibits Inflammasome Activation. ACS chemical biology 53 31525884
2011 Structure-activity relationship studies on isoindoline inhibitors of dipeptidyl peptidases 8 and 9 (DPP8, DPP9): is DPP8-selectivity an attainable goal? Journal of medicinal chemistry 50 21711053
2020 Proteasomal degradation induced by DPP9-mediated processing competes with mitochondrial protein import. The EMBO journal 48 32815200
2016 DPP9 is a novel component of the N-end rule pathway targeting the tyrosine kinase Syk. eLife 46 27614019
2020 Fibroblast Activation Protein (FAP) Overexpression Induces Epithelial-Mesenchymal Transition (EMT) in Oral Squamous Cell Carcinoma by Down-Regulating Dipeptidyl Peptidase 9 (DPP9). OncoTargets and therapy 28 32273729
2022 CCR2 and DPP9 expression in the peripheral blood of COVID-19 patients: Influences of the disease severity and gender. Immunobiology 27 35131543
2022 A Phenotypic Screen Identifies Potent DPP9 Inhibitors Capable of Killing HIV-1 Infected Cells. ACS chemical biology 25 36044633
2017 Involvement of DPP9 in gene fusions in serous ovarian carcinoma. BMC cancer 23 28893231
2018 Saxagliptin but Not Sitagliptin Inhibits CaMKII and PKC via DPP9 Inhibition in Cardiomyocytes. Frontiers in physiology 19 30487758
2017 DPP9 enzyme activity controls survival of mouse migratory tongue muscle progenitors and its absence leads to neonatal lethality due to suckling defect. Developmental biology 19 28887018
2024 DPP9 regulates NQO1 and ROS to promote resistance to chemotherapy in liver cancer cells. Redox biology 18 39094401
2023 Highly Selective Inhibitors of Dipeptidyl Peptidase 9 (DPP9) Derived from the Clinically Used DPP4-Inhibitor Vildagliptin. Journal of medicinal chemistry 16 37721854
2013 DPP8 and DPP9 expression in cynomolgus monkey and Sprague Dawley rat tissues. Regulatory peptides 16 23850796
2016 Dipeptidyl peptidase 9 (DPP9) in human skin cells. Immunobiology 15 27682012
2021 Profibrotic mechanisms of DPP8 and DPP9 highly expressed in the proximal renal tubule epithelial cells. Pharmacological research 14 33932609
2018 Expression and clinical role of the dipeptidyl peptidases DPP8 and DPP9 in ovarian carcinoma. Virchows Archiv : an international journal of pathology 14 30467600
2009 Dipeptidyl peptidase 9 (DPP9) from bovine testes: identification and characterization as the short form by mass spectrometry. Biochimica et biophysica acta 14 20026260
2014 Establishment of a selective evaluation method for DPP4 inhibitors based on recombinant human DPP8 and DPP9 proteins. Acta pharmaceutica Sinica. B 10 26579375
2023 Hemophagocytic lymphohistiocytosis-like hyperinflammation due to a de novo mutation in DPP9. The Journal of allergy and clinical immunology 9 37544411
2008 Association study between adolescent idiopathic scoliosis and the DPP9 gene which is located in the candidate region identified by linkage analysis. Postgraduate medical journal 8 18940951
2024 Pinocembrin activation of DPP9 inhibits NLRP1 inflammasome activation to alleviate cerebral ischemia/reperfusion-induced lung and intestinal injury. Immunologic research 6 39676095
2022 Inflammasome sensor NLRP1 disease variant M1184V promotes autoproteolysis and DPP9 complex formation by stabilizing the FIIND domain. The Journal of biological chemistry 6 36309085
2024 The serine protease DPP9 and the redox sensor KEAP1 form a mutually inhibitory complex. The Journal of biological chemistry 4 39615677
2022 DPP9 as a Potential Novel Mediator in Gastrointestinal Virus Infection. Antioxidants (Basel, Switzerland) 4 36358551
2018 DPP9 enzymatic activity in hematopoietic cells is dispensable for mouse hematopoiesis. Immunology letters 4 29709545
2025 Dipeptidyl peptidase 9 (DPP9) depletion from hepatocytes in experimental primary liver cancer. Biochimica et biophysica acta. Molecular basis of disease 3 40187163
2025 The non-structural protein of SFTSV activates NLRP1 and CARD8 inflammasome through disrupting the DPP9-mediated ternary complex. PLoS pathogens 3 40608794
2024 Study on the correlation between DPP9 rs2109069 and IFNAR2 rs2236757 polymorphisms with COVID-19 mortality. Nucleosides, nucleotides & nucleic acids 3 38660988
2023 The amino-dipeptidyl peptidases DPP8 and DPP9: Purification and enzymatic assays. Methods in enzymology 3 37230592
2019 Immune regeneration in irradiated mice is not impaired by the absence of DPP9 enzymatic activity. Scientific reports 3 31086209
2024 In Silico analysis unveils rs2109069 of DPP9 as a potential catalyst for COVID-19 severity and risk of inflammatory symptoms. Experimental and molecular pathology 2 39615159
2017 Expression, subcellular localisation, and possible roles of dipeptidyl peptidase 9 (DPP9) in murine macrophages. Cell biochemistry and function 2 28256001
2025 DPP8 and DPP9 promote tubular epithelial cell ferroptosis in acute kidney injury. European journal of medical research 1 40665400
2024 Single nucleotide variants in the CCL2, OAS1 and DPP9 genes and their association with the severity of COVID-19 in an Ecuadorian population. Frontiers in cellular and infection microbiology 1 38694517
2024 Cosolvent Molecular Dynamics Applied to DPP4, DPP8 and DPP9: Reproduction of Important Binding Features and Use in Inhibitor Design. Journal of chemical information and modeling 1 39332821
2024 Molecular Targeted Engagement of DPP9 in Rat Tissue Using CETSA, SP3 Processing, and Absolute Quantitation Mass Spectrometry. ACS chemical biology 1 39642389
2023 DPP9 Comes of Age: Highly Selective Inhibitors Promise New Therapeutic Opportunities. Journal of medicinal chemistry 1 37721863
2026 Proximity labeling reveals non-catalytic interactions between DPP9 and ubiquitin signaling complexes. Cellular and molecular life sciences : CMLS 0 41636814
2026 DPP9 inhibition boosts antitumor immunity by disrupting BRISC-mediated PD-L1 expression in clear cell renal cell carcinoma. Cell death and differentiation 0 41826729