Ask about this productRelated genes to: QPCT Blocking Peptide
- Gene:
- QPCT NIH gene
- Name:
- glutaminyl-peptide cyclotransferase
- Previous symbol:
- -
- Synonyms:
- QC, GCT
- Chromosome:
- 2p22.2
- Locus Type:
- gene with protein product
- Date approved:
- 1999-11-16
- Date modifiied:
- 2016-10-05
Related products to: QPCT Blocking Peptide
Related articles to: QPCT Blocking Peptide
- Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive loss of motor neurons. Accurate and accessible blood-based diagnostics for neurodegenerative diseases, including ALS, are being progressively required. Although blood cell gene expression profiles have potential clinical utility for distinguishing ALS, robust transcriptomic biomarkers for supportive diagnosis have not yet been established. Here, we analyzed publicly available peripheral blood mononuclear cell (PBMC) transcriptomic data from ALS patients using Maximum Mean Discrepancy, a kernel-based method that captures nonlinear distributional differences in a reproducing kernel Hilbert space and enables the extraction of informative gene combinations while minimizing multicollinearity, a common issue in multiple regression models. Using this approach, we identified a nonlinear three-gene combination-PRKAR1A, QPCT, and TMEM71-that distinguished ALS from healthy controls with an area under the curve (AUC) of 0.83 in a public PBMC dataset. This achievement was confirmed in laboratory PBMC samples with an AUC of 0.85, supporting the robustness of the identified gene signature in independent samples. Furthermore, these genes also enabled ALS classification in induced pluripotent stem cell-derived motor neurons with an AUC of 0.79. Knockdown of PRKAR1A, QPCT, or TMEM71 in motor neurons increased the TDP-43 expression levels, and PRKAR1A knockdown induced the mislocalization of TDP-43, accompanied by phosphorylation, suggesting a potential link to ALS-related pathophysiology. These findings suggest that nonlinear gene combinations may provide a useful strategy for identifying blood-based biomarkers and offer insights into ALS pathogenesis. This nonlinear, data-driven analytical framework enabled the transition from unbiased gene discovery to the identification of pathophysiology-associated molecules by in vitro functional validation. - Source: PubMed
Publication date: 2026/05/11
Imamura KeikoNagahashi AyakoOkusa AyaYamamoto TakuyaIzumi YuishinUeda NaonoriKawahara YoshinobuInoue Haruhisa - Cystic fibrosis (CF) is a genetic disorder caused by CFTR mutations, most commonly ΔF508, leading to defective ion transport and multisystem pathology. Small-molecule modulators partially restore mutant CFTR function, but therapeutic efficacy remains limited, particularly for N1303K mutation refractory to current treatments. Here, we show that inhibition of the glutaminyl-peptide cyclotransferase (QPCT)-dependent pathway rescues both the surface expression and functional activity of ΔF508 CFTR. Integrated molecular and physiological analyses identify protein disulfide-isomerase A4 (PDIA4) as a key mediator of this process through a pyroglutamate (pGlu)-dependent association with misfolded ΔF508 CFTR. QPCT-dependent pGlu modification promotes the association of PDIA4 with mutant CFTR within the endoplasmic reticulum (ER) quality control machinery, whereas inhibition of QPCT disrupts this interaction, relieving ER retention and enabling a fraction of ΔF508 CFTR to reach the cell surface. Furthermore, inhibition of QPCT also restores the function of the N1303K CFTR mutant, indicating a broader relevance of this pathway in regulating CFTR proteostasis. These findings provide evidence for an ER quality control mechanism governing mutant CFTR fate and suggest potential therapeutic strategies for CFTR mutations that are unresponsive to existing modulators. - Source: PubMed
Publication date: 2026/06/09
Sun LeRodriguez LarryPankow SandraDiedrich JoleneQin KeZhang JiananWu XuWu PengYates John R - Glutaminyl-peptide cyclotransferase (QPCT, QC) and its isoenzyme glutaminyl-peptide cyclotransferase-like protein (QPCTL, isoQC) are zinc-dependent enzymes that post-translationally catalyze the conversion of N-terminal glutamine or glutamate residues into pyroglutamate (pGlu). The pGlu modification impacts protein-protein interactions, enhances protein stability, and protects proteins from proteolytic degradation. QPCTL and QPCT differ in their subcellular localization, with QPCTL being retained in the Golgi apparatus and QPCT being active in secretory vesicles. Current research focuses on the impact of QPCTL-mediated pGlu formation in cancer and neurodegenerative disorders such as Alzheimer's disease. In cancer, QPCTL is a promising immunotherapy target since QPCTL-mediated CD47 pyroglutamylation prevents macrophages from phagocytosing tumor cells. Moreover, QPCTL shapes the tumor microenvironment by modulating macrophage recruitment and polarization through modification of CCL2. However, QPCTL modulates Butyrophilins on tumor cells and thereby promote their detection and killing by γδ T cells. Hence, QPCTL significantly affects cancer progression, inflammatory processes, and immune regulation. These insights highlight QPCTL's potential as a therapeutic target in oncology, metabolic diseases, and immune-mediated disorders. In this review, we highlight the role of QPCTL in tumor evasion and immune modulation. Moreover, we provide a comprehensive overview about predicted and validated substrates of QPCT/L and about the relevance of QPCT/L in various diseases. - Source: PubMed
Publication date: 2026/03/26
Smid Hannah ElaineColotti JanaNölp SophiaArlt Nike SophiaWeber SophieGumann Amelievon Hörsten StephanKarow AxelSchuh Wolfgang - There is a need for novel therapies for diabetic retinopathy (DR) because existing therapies treat only certain features of DR and do not work optimally for all patients. While proteomic studies provide insight into disease pathobiology, they are often limited to small sample sizes due to high costs, limiting their generalizability and reproducibility. Moreover, they often yield lists of tens to hundreds of proteins with differential expression, making it difficult to prioritize the most biologically relevant biomarkers beyond using arbitrary fold-change and false-detection rate cutoffs. Here, we applied a two-stage multimodal AI approach: first, we integrated EHR and proteomics data to rationally prioritize candidate protein biomarkers and, next, validated these biomarkers in an independent cohort. These protein biomarkers of DR are rooted in the EHR data and thereby more likely to be biological drivers of disease. - Source: PubMed
Publication date: 2026/02/24
Lin Jonathan BMataraso Samson JChadha MadhumeetaVelez GabrielMruthyunjaya PrithviAghaeepour NimaMahajan Vinit B - The global incidence of ulcerative colitis (UC), a chronic inflammatory bowel disease, is rising. Epi-berberine (EPI), an alkaloid from Coptidis Rhizoma, shows potential for UC treatment. This study aimed to assess EPI's effect on UC and explore the mechanism underlying its UC-alleviating effect. The therapeutic effects of EPI on UC were validated in dextran sulfate sodium (DSS)-induced colitis mice and lipopolysaccharide (LPS)-induced Caco-2 inflammatory models and further investigated the underlying mechanism. In vivo, high-dose EPI (200 mg/kg) attenuated weight loss, reduced disease activity index, increased colon length, lowered colon macroscopic/histological scores, restored intestinal mucosal barrier and inhibited colonic inflammation. EPI (25/50 μM) had similar in vitro effects. mRNA-seq identified EPI-regulated genes in UC mice, revealing six gene clusters with analogous expression patterns. The largest cluster contained genes upregulated by DSS but downregulated by EPI, potentially involved in the MAPK pathway. Key DEGs were enriched in PI3K-Akt and MAPK pathways, verified in vivo and in vitro. Literature retrieval and molecular docking predicted glutaminyl-peptide cyclotransferase (QPCT) as EPI's potential UC therapeutic target. EPI inhibited DSS/LPS-induced QPCT upregulation in vivo and in vitro; QPCT knockdown suppressed inflammation and preserved Caco-2 monolayer barrier function, while QPCT overexpression reversed EPI's therapeutic effects. QPCT mediates PI3K-Akt/MAPK activation, and its overexpression abrogated EPI's inhibitory effects. EPI alleviates murine UC by protecting the intestinal mucosal barrier and inhibiting inflammation, likely via regulating the QPCT-PI3K-Akt/MAPK pathway. It provides a preclinical basis for developing prophylactic strategies for inflammatory bowel disease. - Source: PubMed
Publication date: 2026/03/12
Chen BingyuLiu KeGuo YayaZhao JingweiWang Yanhua