The DNAJB11 Knockout SK-HEP-1 Polyclonal Cells product comprises a CRISPR/Cas9-edited polyclonal population of SK-HEP-1 cells with targeted disruption of the DNAJB11 gene. This loss-of-function model enables investigation of endoplasmic reticulum (ER) proteostasis pathways in a human hepatic adenocarcinoma background. Unlike monoclonal cell lines, the polyclonal format retains population-level heterogeneity while eliminating target gene function across the pool, providing a robust tool for studying ER stress responses without clonal selection artifacts.
The parental SK-HEP-1 cell line is a well-established human hepatic adenocarcinoma model derived from ascitic fluid of a patient with liver cancer. SK-HEP-1 cells exhibit epithelial morphology and are widely utilized in hepatocellular carcinoma research, including studies of tumorigenesis, metastasis, and drug sensitivity. These cells provide a physiologically relevant platform for interrogating liver cancer-associated molecular mechanisms, particularly those involving ER stress and the unfolded protein response (UPR).
DNAJB11 (ERdj3) encodes an ER-resident DnaJ co-chaperone that regulates the ATPase activity of BiP (HSPA5), facilitating recognition and processing of misfolded proteins. Under basal conditions, DNAJB11 assists in protein folding and quality control by delivering substrates to BiP and the ER-associated degradation (ERAD) machinery. ER stressors such as tunicamycin or thapsigargin activate the UPR sensors ATF6, IRE1, and PERK, altering the expression of DNAJB11 and its partners. DNAJB11 interacts directly with BiP and with chaperones including GRP94, calnexin, and protein disulfide isomerases, thereby modulating the balance between refolding and degradation. Downstream UPR effectors, including spliced XBP1 and CHOP, are impacted by DNAJB11 function, linking its activity to cell survival or apoptosis decisions.
In the SK-HEP-1 liver cancer model, DNAJB11 knockout is predicted to sensitize cells to ER stress-induced apoptosis, as attenuated co-chaperone activity impairs BiP-mediated refolding and ERAD, leading to unresolved stress signaling. This reflects the heightened vulnerability of rapidly dividing cancer cells to proteotoxic stress, making the knockout a useful system for studying synthetic lethality with chemotherapeutics or ER stress inducers. Additionally, DNAJB11 disruption may influence liver cancer cell adaptation to microenvironmental stressors, providing insights into tumor progression and drug resistance mechanisms.
Researchers can employ these polyclonal knockout cells for a range of assays, including Western blotting for UPR markers (BiP, CHOP), RT-qPCR to monitor XBP1 splicing, co-immunoprecipitation of BiP complexes, and apoptosis or viability assays following treatment with tunicamycin or other ER stressors. The model is suitable for functional dissection of ER proteostasis, chaperone networks, and their roles in liver cancer biology. For additional information, technical support, or ordering details, please contact Ascent Research.
