The DPP9 Knockout 786-O Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout population generated from the 786-O human renal cell adenocarcinoma line, in which the DPP9 gene is disrupted. This polyclonal format provides a heterogeneous loss-of-function model, avoiding clonal selection artifacts and enabling robust functional studies of DPP9-dependent processes.
The 786-O parental cell line harbors a biallelic VHL mutation and serves as a well-established model for clear cell renal cell carcinoma (ccRCC), characterized by constitutive HIF pathway activation and pseudohypoxic signaling. This VHL-deficient background is ideal for investigating molecular interactions relevant to renal cancer biology.
DPP9 encodes a serine dipeptidyl peptidase that cleaves N-terminal dipeptides from peptide substrates, functioning in antigen processing and peptide catabolism. A critical role of DPP9 is the negative regulation of the NLRP1 inflammasome: under basal conditions, DPP9 interacts with NLRP1 and restrains its oligomerization, preventing ASC recruitment and caspase-1 activation. Genetic disruption of DPP9 removes this inhibition, permitting NLRP1-dependent ASC speck formation, caspase-1 autoprocessing, and subsequent maturation of the pro-inflammatory cytokines IL-1?? and IL-18. DPP9 expression is upregulated by interferon-?? and NF-??B in response to stress signals, and it interacts with molecular chaperones and ubiquitin-like proteins. Beyond inflammasome control, DPP9 modulates apoptosis by interacting with pro-apoptotic factors, and its loss can sensitize cells to programmed cell death.
In the 786-O ccRCC model, characterized by constitutive HIF pathway activation due to VHL loss, this DPP9 knockout population provides a powerful tool to dissect the intersection between hypoxia-driven signaling and DPP9-mediated inflammasome and apoptosis regulation. The dual perturbation of VHL and DPP9 may influence tumor cell survival, immune evasion, and response to therapeutic agents.
Applications include investigating DPP9 function in renal cell carcinoma pathogenesis, NLRP1 inflammasome dynamics, immune evasion mechanisms, and DPP9 druggability. Representative assays include western blotting for DPP9, NLRP1, and caspase-1 activation; DPP9 enzymatic activity measurements; ASC speck visualization; IL-1?? and IL-18 ELISAs; apoptosis and viability assays; and cell migration studies. For additional product information or technical support, please contact Ascent Research.
