The JAGN1 Knockout NCI-H1975 Polyclonal Cells represent a CRISPR/Cas9-edited polyclonal cell population derived from the NCI-H1975 human lung adenocarcinoma cell line, carrying a targeted disruption of the JAGN1 gene. This loss-of-function model provides a robust tool for investigating the roles of JAGN1 in protein N-glycosylation, endoplasmic reticulum (ER) homeostasis, and associated cellular processes. The polyclonal nature of the knockout pool preserves population-level heterogeneity while ensuring consistent ablation of JAGN1 function, suitable for a wide range of biochemical and functional assays.
The parental NCI-H1975 cell line was originally established from the pleural effusion of a female patient with lung adenocarcinoma, and it is characterized by MET amplification and a PIK3CA activating mutation. As a widely used model of non-small cell lung adenocarcinoma, NCI-H1975 cells exhibit dependence on receptor tyrosine kinase and PI3K/AKT signaling, making them particularly relevant for studying how alterations in glycosylation may intersect with oncogenic pathways. This genetic background offers a unique context for examining JAGN1-dependent cellular phenotypes.
JAGN1 encodes a subunit of the oligosaccharyltransferase (OST) complex, interacting directly with catalytic components STT3A and STT3B, as well as accessory subunits DDOST, RPN1, and RPN2. The OST complex catalyzes en bloc transfer of dolichol-linked oligosaccharides to nascent polypeptides, a critical step in N-glycosylation within the ER. JAGN1 expression is transcriptionally regulated by G-CSF (CSF3), CEBPA, and SPI1, and is modulated by ER stress sensors ATF6, ERN1 (IRE1??), and EIF2AK3 (PERK). JAGN1 loss impairs OST function, causing hypoglycosylation, UPR induction (upregulating DDIT3 and HSPA5), and CASP3-mediated apoptosis. Its interaction with ER chaperone HSPA5 coordinates glycosylation with quality control mechanisms, including the calnexin/calreticulin cycle and EDEM1-mediated degradation of misfolded glycoproteins.
Within the NCI-H1975 lung adenocarcinoma background, JAGN1 knockout provides a powerful model to dissect the contribution of N-glycosylation to cancer cell biology. Since MET and PI3K signaling often rely on properly glycosylated receptors and downstream effectors, this polyclonal knockout population enables investigation into how impaired glycosylation affects oncogenic signal transduction, cell surface protein stability, and tumor immune evasion. Moreover, the interplay between ER stress and apoptosis induced by JAGN1 loss may reveal vulnerabilities specific to lung adenocarcinoma cells, potentially informing therapeutic strategies that target the glycosylation machinery or UPR pathways.
Researchers can employ this knockout model for a diverse array of applications, including mechanistic studies of protein N-glycosylation in cancer progression, glycoproteomic profiling using mass spectrometry, and functional assays of ER stress and UPR signaling. The cells are particularly suited for modeling severe congenital neutropenia in vitro, as JAGN1 deficiency is known to impair granulocytic differentiation and survival; relevant readouts include flow cytometric analysis of apoptosis and qPCR quantification of ER stress markers such as DDIT3 and HSPA5. Additional experimental contexts include drug screening for compounds that restore glycosylation or mitigate ER stress, and lectin blotting or western blotting to assess global and specific glycoprotein levels. For further technical specifications and availability, please contact Ascent Research.
