Ask about this productRelated genes to: DPP9 antibody
- Gene:
- DPP9 NIH gene
- Name:
- dipeptidyl peptidase 9
- Previous symbol:
- -
- Synonyms:
- -
- Chromosome:
- 19p13.3
- Locus Type:
- gene with protein product
- Date approved:
- 2002-05-21
- Date modifiied:
- 2016-02-08
Related products to: DPP9 antibody
Related articles to: DPP9 antibody
- Over the past five decades, air pollution has posed a growing threat to human health, particularly affecting the respiratory system. This study aims to investigate the potential molecular mechanisms underlying the relationship between exposure to air pollutants and the development of COPD and to identify potential gene targets that may play a key role in this process. In this study, researchers used several publicly available databases to obtain target genes related to air pollutants and COPD, determine the overlapping genes between them and performed GO and KEGG enrichment analyses to elucidate the underlying mechanisms. Cross-validation was performed using multiple datasets from the Gene Expression Omnibus (GEO) database to screen out candidate targets, and molecular docking techniques were utilized to investigated molecular interactions between candidate targets and air pollutants. Candidate targets were subsequently validated and analyzed using immune cell infiltration analysis, single-cell transcriptome data, risk prediction model construction and clinical data to further elucidate their relationship with COPD. Findings suggest that HDAC9, DPP9 and KCNN4 are candidate targets of air pollutants that are potentially involved in COPD development. These results offer new insights into the potential molecular mechanisms linking air pollution exposure to COPD and underscore the need for further in-depth research on air pollution issues. - Source: PubMed
Song DongXie LinGao XuegeChen YushanZhong ChunjunLi HuicongZhan ShaofengLian Leshen - Programmed cell death protein 1 (PD-1) and its ligand programmed cell death ligand-1 (PD-L1) are key mediators of immune checkpoint blockade therapy in clear cell renal cell carcinoma (RCC). However, immune evasion and primary resistance often limit their efficacy, highlighting the need for improved strategies. Here, we identified dipeptidyl peptidase 9 (DPP9) as a critical regulator of PD-L1 expression in ccRCC. Pharmacological inhibition of DPP9 with 1G244 restores T cell cytotoxicity and enhances checkpoint blockade efficacy. Mechanistically, DPP9 disrupts the BRISC-SHMT2 complex, enhancing BRISC-mediated deubiquitination and stabilization of IFNAR1, which activates the JAK/STAT pathway and drives PD-L1 transcription. 1G244 reverses this process by reducing DPP9 interacting with SHMT2, promoting IFNAR1 ubiquitination and degradation, thereby reducing PD-L1 levels and restoring T cell-mediated cytotoxicity. Moreover, the combination of 1G244 and anti-CTLA-4 therapy further enhanced antitumor immunity, highlighting a potential synergistic therapeutic strategy. Collectively, our findings define a novel DPP9-BRISC-SHMT2 regulatory axis in PD-L1 transcriptional control and identify 1G244 as an alternative combinatorial strategy to enhance the efficacy of cancer immunotherapy. - Source: PubMed
Publication date: 2026/03/14
Zhang WeiWang YueFeng TaoCai TingtingWang WenfengZhu ShuxuanChen YingjiZhang HailiangYe DingweiWang ChenjiChang Kun - In recent years, the prevalence of diabetic nephropathy (DN) has been increasing year by year. Here, this experiment investigated the effects of PFKFB2 in DN and its molecular mechanisms of DN. DN mice were fed a high-fat diet for 12 weeks, and then injected with STZ. DN mice were transfected with negative or sh-DPP9 lentivirus using Lipofectamine 3000 (Invitrogen, Carlsbad, CA, USA). Human proximal tubular HK-2 cells stimulated with 20 mmol/L d-glucose. Analysis revealed a significant downregulation of PFKFB2 expression in DN patients. PFKFB2 was expression in renal cell of DN model using single-cell RNA sequencing. Sh-PFKFB2 aggravated DN in mice model. PFKFB2 up-regulation reduced oxidative stress and glycolysis in model of DN. The inhibition of PFKFB2 aggravated mitochondria-dependent ferroptosis in model of DN. Ferroptosis inhibitor reduced the effects of PFKFB2 down-regulation in mitochondria-dependent ferroptosis in model of DN. PFKFB2 suppressed HIF-1α expression in model of DN by the inhibition of HIF-1α ubiquitination. HIF-1α inhibitor reduced the effects of PFKFB2 down-regulation in mitochondria-dependent ferroptosis in model of DN. In conclusion, PFKFB2 reduced oxidative stress and glycolysis of DN through the inhibition of HIF-1α signaling pathway by the induction of Nrf2 ubiquitination, further elucidating the role of PFKFB2 regulated mitochondrial ROS-induced ferroptosis for DN. Targeting PFKFB2 is thus a potentially effective therapeutic strategy for DN. - Source: PubMed
Tan YayinZhou JiajunLiu Yong - Dipeptidyl peptidase 9 (DPP9) is an amino-peptidase with roles in immunity, DNA-repair, cell signaling, memory and neonatal survival; its dysregulation is linked to cancer and immune-related disorders. While many studies focus on its catalytic activity, scaffolding functions of DPP9 are emerging. Here, we mapped the DPP9 interactome using TurboID-based proximity labeling in DPP9 knock-out HEK293 cells reconstituted with doxycycline-inducible miniTurboID-DPP9, allowing fine-tuned expression that approximates physiological levels. Besides known partners, proteins involved in autophagy, mRNA decay and ubiquitin signaling along with DPP8, were strongly enriched among the identified DPP9 binding partners. Notably, we validated DPP8, the E3 ligase CBL, the deubiquitinase complex CYLD-SPATA2 and the BRISC complex components BRCC36/BRCC3 and ABRO1/ABRAXAS2 as novel DPP9 interactors. Furthermore, NanoBRET assays in living cells demonstrated that DPP9 disrupts the binding between BRCC36/BRCC3 and ABRO1/ABRAXAS2, and the interaction of CYLD with SPATA2, thereby compromising these protein-protein interactions. Mechanistically, these findings reveal physical and potentially regulatory interactions between DPP9 and components of the ubiquitin system and provide a basis for dissecting the non-catalytic functions of DPP9. - Source: PubMed
Publication date: 2026/02/04
Wirtgen Valentina ElenaSaied LaylaZolg SamuelAlonso Marta CamposMayer BettinaDonzelli LauraMaurer UlrichTimmers H T MarcKnobeloch Klaus-PeterKleifeld OdedGeiss-Friedlander Ruth - Chronic kidney disease (CKD), characterized by structural, functional, and metabolic derangements, remains a leading cause of end-stage renal disease (ESRD) with profound global health burdens. The kidney's high oxygen demand for blood filtration renders it exquisitely sensitive to redox imbalance-an aberration common to both CKD and acute kidney injury (AKI) that, when coupled with iron dysregulation, unleashes ferroptosis: a non-apoptotic, iron-dependent form of regulated cell death driven by iron accumulation, lipid peroxidation, and antioxidant defense impairment (e.g., GPX4/SLC7A11 dysfunction), cascades to which the redox-sensitive kidney is uniquely predisposed. While ferroptosis has been linked to AKI, diabetic nephropathy (DN), and renal fibrosis, existing reviews largely suffer from two limitations: they either focus on single kidney disease entities (e.g., only AKI or DN) or reiterate generic ferroptosis mechanisms, lacking a unified pathophysiological framework that bridges acute insults, chronic fibrosis, and even renal carcinogenesis. Addressing this gap, this review offers three integrated contributions: first, it positions ferroptosis as a convergent metabolic executioner across a broader spectrum of kidney diseases-encompassing AKI, DN, renal interstitial fibrosis, systemic lupus erythematosus (SLE) nephritis, autosomal dominant polycystic kidney disease (ADPKD), renal cell carcinoma (RCC), and contrast-induced nephropathy (CIN)-while emphasizing cell type-specific vulnerabilities: tubular epithelial cells (susceptible via mitochondrial dysfunction), podocytes (via iron overload), and immune cells (e.g., neutrophils/macrophages in SLE nephritis) exhibit context-dependent ferroptosis regulation, governed by cell type-specific modulators [e.g., Nrf2 in tubules, heme oxygenase-1 (HO-1) in macrophages, and sirtuins in podocytes]. Second, it reconciles seemingly disparate findings through a redox-metabolic lens-e.g., dual roles of HO-1 (protective via heme degradation . pro-ferroptotic via iron release) or iron overload (driving injury in AKI . targeted therapy in RCC)-by clarifying disease-specific regulatory mechanisms: PKD1 mutation-driven mitochondrial defects in ADPKD, DPP9-Nrf2-mediated sorafenib resistance in RCC, and PPARα-FABP1 axis dysregulation in IgA nephropathy, alongside shared core pathways (e.g., GPX4/SLC7A11 as central checkpoints). Third, it integrates translational insights rarely synthesized in prior work: mapping natural compounds (icariin II and artesunate), repurposed drugs (sorafenib and melatonin), and novel modulators to disease stages (e.g., Lip-1 for fibrosis and salinomycin for RCC stem cells); highlighting strategies to reverse ferroptosis-related drug resistance (targeting DPP9 in RCC); and identifying ferroptosis-related genes (ACSL4 and PDIA4) as prognostic biomarkers. Accumulating clinical and experimental evidence confirms ferroptosis as a pivotal driver of kidney disease onset and progression. This review not only synthesizes ferroptosis pathophysiology and research advances but also delineates disease-tailored therapeutic strategies. By addressing key knowledge gaps-crosstalk between ferroptosis and other cell death modalities (e.g., pyroptosis), lack of kidney-specific clinical biomarkers, and underexplored roles in autoimmune nephritides-it provides a conceptual roadmap for mechanism-based diagnostics, precision therapeutics, and rational drug combinations, transcending traditional disease boundaries to advance clinical translation for both primary and secondary kidney diseases. - Source: PubMed
Publication date: 2025/12/05
Luo YanfangLong MuyangWu XueqinZeng Liuting