The DNAJB9 Knockout MES-OV Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population derived from the MES-OV human ovarian carcinoma epithelial cell line. This product consists of a heterogeneous pool of cells carrying targeted disruptions in the DNAJB9 gene, generated via CRISPR/Cas9-mediated genome editing. The polyclonal nature captures cellular heterogeneity inherent to cancer populations, providing a loss-of-function model for studying DNAJB9-dependent mechanisms.
MES-OV is an adherent epithelial cell line established from malignant ovarian cancer tissue, serving as a clinically relevant in vitro model for ovarian carcinoma. It retains key oncogenic features, including dysregulated growth and survival pathways, and is widely used to investigate tumor biology, metastasis, and chemotherapeutic responses, particularly to platinum-based agents like cisplatin.
DNAJB9 (ERdj4) is an ER-resident Hsp40 co-chaperone that promotes endoplasmic reticulum-associated degradation (ERAD) of misfolded proteins, thereby alleviating ER stress. It functions as a cofactor for the Hsp70 chaperone BiP (HSPA5/GRP78), selecting clients and presenting them to the HRD1-SEL1L ubiquitin ligase complex for retrotranslocation and proteasomal degradation. DNAJB9 expression is strongly induced by the unfolded protein response (UPR) transcription factors spliced XBP1 (XBP1s) and ATF6 during ER stress triggered by tunicamycin, thapsigargin, hypoxia, or nutrient deprivation. DNAJB9 interacts with SYVN1 (HRD1), SEL1L, OS9, VCP/p97, and DERL1, and its activity enhances clearance of misfolded clients, reducing pro-apoptotic CHOP levels and dampening IRE1?? and ATF6 branch signaling to support cell survival.
In ovarian cancer, where constitutive ER stress from genomic instability and rapid proliferation drives malignant progression, DNAJB9 likely enables tumor cells to evade apoptosis by bolstering ERAD capacity. Disruption of DNAJB9 in MES-OV cells creates a valuable model to examine how loss of this co-chaperone sensitizes cells to ER stress-inducing agents and chemotherapeutics. Researchers can explore the dependency of ovarian cancer on DNAJB9 for survival under proteotoxic conditions, probing mechanisms of chemoresistance and identifying potential therapeutic vulnerabilities.
This polyclonal knockout model supports diverse applications, including identification of DNAJB9 substrates via co-immunoprecipitation, analysis of UPR signaling through western blotting for BiP, CHOP, and XBP1s, and RT-qPCR of UPR target genes. It is suitable for viability (MTT) and apoptosis (Annexin V) assays following tunicamycin or cisplatin treatment, proteasome activity measurements, immunofluorescence for ER stress markers, and migration studies. The cells are also ideal for drug sensitivity profiling and functional validation of ER stress as a therapeutic target in ovarian cancer. For additional details, please contact Ascent Research.
