The DNAJB11 Knockout A2780 Polyclonal Cells represent a CRISPR/Cas9-edited polyclonal knockout cell population designed for investigating ER proteostasis and unfolded protein response (UPR) pathways in an ovarian cancer context. This product consists of the human ovarian adenocarcinoma cell line A2780 engineered to disrupt the DNAJB11 gene, which encodes an endoplasmic reticulum (ER)-resident co-chaperone. The mixed population captures the heterogeneity of CRISPR/Cas9-mediated gene disruption, providing a robust loss-of-function model without selection of individual clones. Researchers can utilize this system to study the functional consequences of DNAJB11 depletion in a disease-relevant cellular background.
The A2780 parental cell line was established from an untreated patient with ovarian adenocarcinoma and serves as a widely employed model for epithelial ovarian carcinoma. These cells recapitulate key features of high-grade serous ovarian cancer, including sensitivity to platinum-based chemotherapeutics and the potential to develop drug resistance. Their well-characterized genomic and transcriptomic landscape makes A2780 cells an ideal platform for interrogating gene function in ovarian cancer biology, particularly in the context of stress adaptation and therapeutic response.
DNAJB11 functions as an ER co-chaperone that partners with BiP (HSPA5) to promote protein folding and triage misfolded clients toward ER-associated degradation (ERAD). It is activated by ER stress stimuli such as tunicamycin and thapsigargin and operates downstream of the UPR sensors IRE1??, PERK, and ATF6. DNAJB11 loss is predicted to impair ER proteostasis, leading to accumulation of unfolded proteins and heightened UPR signaling. Key downstream effectors affected by its depletion include XBP1 splicing, ATF4 translation, and CHOP (DDIT3) expression, which collectively influence cell fate decisions between survival and apoptosis. Additionally, DNAJB11 interacts with ERAD machinery components like Derlin-1 and p97, underscoring its role in protein quality control.
In A2780 ovarian cancer cells, DNAJB11 knockout renders the ER proteostasis network vulnerable, potentially sensitizing cells to chemotherapeutic agents that induce ER stress, such as cisplatin and the proteasome inhibitor bortezomib. This model is thus uniquely suited to explore how disruptions in protein folding and UPR signaling contribute to drug resistance mechanisms frequently observed in ovarian carcinoma. By compromising the cell’s ability to manage misfolded proteins, the knockout may shift the balance toward pro-apoptotic UPR signaling, providing a tool to examine synthetic lethal interactions and to identify vulnerabilities that can be exploited therapeutically.
Typical applications include Western blotting for UPR markers (BiP, CHOP), qPCR-based monitoring of XBP1 splicing, cell viability assays under tunicamycin-induced ER stress, Annexin V staining for apoptosis, co-immunoprecipitation of DNAJB11-interacting proteins, immunofluorescence visualization of ER stress markers, and transcriptome-wide RNA-seq analyses. Furthermore, the knockout cells enable drug sensitivity profiling against cisplatin and bortezomib to investigate combination treatment strategies. This product is suitable for detailed mechanistic studies of ER proteostasis in cancer and for high-throughput screening campaigns seeking modulators of the UPR. For additional information or assistance with experimental design, please contact Ascent Research.
