The DNAJB9 Knockout NCI-H1975 Polyclonal Cells represent a CRISPR/Cas9-edited polyclonal cell population engineered for disruption of the DNAJB9 gene in the human lung adenocarcinoma NCI-H1975 cell line. This polyclonal knockout pool provides a heterogeneous collection of loss-of-function alleles, enabling robust assessment of DNAJB9-dependent phenotypes without the clonal biases associated with single-cell-derived lines.
The NCI-H1975 cell line originates from a human female with non-small cell lung adenocarcinoma and serves as a widely used model for lung cancer research. These cells harbor characteristic mutations and exhibit typical adenocarcinoma morphology and growth properties, making them suitable for investigating oncogenic signaling and treatment resistance mechanisms.
DNAJB9 encodes an ER-resident co-chaperone that critically regulates the unfolded protein response (UPR) and ER-associated degradation (ERAD). As a member of the HSP40 family, DNAJB9 interacts with the HSP70 chaperone BiP (HSPA5) and the retrotranslocation complex components Derlin-1 and VCP/p97 to facilitate clearance of misfolded proteins. DNAJB9 expression is induced by ER stress through the IRE1-XBP1 and ATF6 branches of the UPR, while its deficiency impairs ERAD substrate processing, leading to accumulation of unfolded proteins and altered downstream signaling via PERK-eIF2??-ATF4-CHOP pathways. This positions DNAJB9 at a key node between ER stress sensing and proteostasis maintenance.
Disruption of DNAJB9 in NCI-H1975 cells creates a valuable model to dissect ER proteotoxicity in lung adenocarcinoma. Cancer cells often exploit UPR components to survive under high secretory and metabolic demands; loss of DNAJB9 may sensitize these cells to ER stress-induced apoptosis or alter their response to chemotherapeutics. By eliminating DNAJB9 function, researchers can investigate how co-chaperone-mediated ERAD contributes to tumor cell fitness and drug resistance, potentially revealing vulnerabilities in protein quality control pathways.
This polyclonal knockout cell pool is ideally suited for a wide range of functional studies, including quantitative RT-PCR and Western blot analyses of UPR markers (e.g., XBP1 splicing, CHOP induction), ER stress induction assays with tunicamycin or thapsigargin, cell viability and apoptosis measurements under proteotoxic challenge, and co-immunoprecipitation to probe chaperone interactions. The heterogeneous knockout population facilitates improved statistical power in screening applications and allows monitoring of phenotypic consistency across different editing events. For further details or customized solutions, please contact Ascent Research.
