The DNAJC3 Knockout MES-OV Polyclonal Cells product is a CRISPR/Cas9-edited polyclonal cell population derived from the MES-OV human ovarian endometrioid carcinoma cell line, featuring targeted disruption of the DNAJC3 gene. This loss-of-function model is designed to facilitate investigation of the unfolded protein response (UPR) and PERK signaling within the context of epithelial ovarian cancer. The polyclonal format provides a heterogeneous pool of edited cells, enabling robust and reproducible assessment of DNAJC3-dependent phenotypes without clonal selection artifacts.
The MES-OV host cell line was established from a patient-derived epithelial ovarian endometrioid carcinoma, representing a clinically relevant model for ovarian cancer research. These cells retain key characteristics of the original tumor, including epithelial morphology and the capacity to respond to endoplasmic reticulum (ER) stress. MES-OV is widely utilized in studies of cancer cell survival, drug resistance, and signal transduction, making it an ideal background for genetic perturbation of ER stress regulators such as DNAJC3.
DNAJC3 encodes the co-chaperone P58IPK, which functions as a critical negative regulator of the UPR by directly binding and inhibiting the PERK (EIF2AK3) kinase. Under ER stress conditions, P58IPK association with PERK attenuates phosphorylation of the eukaryotic translation initiation factor eIF2??, thereby dampening activation of the transcription factor ATF4 and suppressing expression of the pro-apoptotic factor CHOP. This regulatory node is further modulated by interactions with molecular chaperones including BiP/GRP78 and HSP70, and cross-talk with the IRE1 and ATF6 branches of the UPR. Consequently, DNAJC3 plays a pivotal role in maintaining ER homeostasis and promoting cell survival during proteotoxic stress.
In the MES-OV ovarian cancer background, disruption of DNAJC3 is particularly significant given the heightened basal ER stress often exhibited by tumor cells due to rapid proliferation and aneuploidy. Loss of DNAJC3-mediated PERK inhibition would be predicted to dysregulate the PERK-eIF2??-ATF4-CHOP axis, sensitizing cells to ER stress-induced apoptosis. This model thus enables dissection of how ovarian cancer cells adapt to chronic ER stress and the specific contribution of DNAJC3 to tumor cell viability and chemoresistance.
Researchers can employ this knockout polyclonal population to interrogate PERK pathway dynamics using phosphorylation-specific western blotting for PERK and eIF2??, as well as RT-qPCR quantification of UPR target genes such as ATF4 and CHOP. Functional assays may include apoptosis measurements under ER stress induction by tunicamycin or thapsigargin, and drug sensitivity studies targeting UPR components. Applications extend to investigating the interplay between ER stress and ovarian cancer pathogenesis, evaluating potential synthetic lethal interactions, and screening therapeutic agents that exploit UPR vulnerabilities. For additional information or technical support, please contact Ascent Research.
