The DTX3L Knockout NCI-H1299 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population derived from the NCI-H1299 non-small cell lung carcinoma line. This product offers a heterogeneous pool of cells with disrupted DTX3L, enabling loss-of-function studies in a disease-relevant background without clonal bias.
NCI-H1299 is an epithelial cell line derived from a lymph node metastasis of a lung carcinoma in a 43-year-old male. It serves as a well-characterized model for NSCLC, particularly for investigating metastatic progression and immune-related signaling in advanced lung cancer. This metastatic origin provides a pertinent host environment for analyzing DTX3L??s immunological roles.
DTX3L encodes an E3 ubiquitin ligase that, together with PARP9, forms a complex central to interferon-driven innate immunity. It is activated by interferon-alpha and interferon-gamma via the IFNAR-JAK1/TYK2-STAT1/STAT2-IRF9 axis, leading to ISRE-mediated transcription of ISGs. DTX3L directly ubiquitinates histone H2A and signaling proteins such as MAVS and STING, and interacts with STAT1 to modulate antiviral responses. Its disruption abrogates these ubiquitination events, attenuating interferon signaling and compromising the cellular antiviral state, which may enhance susceptibility to viral oncolysis or alter tumor immune recognition.
In NCI-H1299 NSCLC cells, DTX3L knockout perturbs ubiquitin-dependent regulation of interferon and NF-kB pathways, potentially impacting tumor immunogenicity and interferon responsiveness. This model is instrumental for studying innate immune evasion in lung cancer and for testing oncolytic virus therapies, given the impaired antiviral defenses. The polyclonal population reflects tumor heterogeneity, offering a physiologically relevant tool for preclinical research.
Applications include co-immunoprecipitation to probe the DTX3L-PARP9 complex, RT-qPCR for ISG expression, ubiquitination assays, and interferon stimulation experiments. These cells are suitable for viral infection assays to evaluate oncolytic susceptibility and for drug screens targeting JAK-STAT modulators. Standard readouts such as Western blotting for DTX3L and phosphorylated STAT1 are supported. For additional inquiries, please contact Ascent Research.
