The DNAJC3 Knockout A2780 Polyclonal Cells product provides a CRISPR/Cas9-edited polyclonal population of A2780 epithelial ovarian cancer cells in which the DNAJC3 gene has been disrupted. This polyclonal knockout cell pool enables loss-of-function studies of DNAJC3 without requiring clonal isolation, offering a representative model to examine the gene’s function at the population level. The product is intended for advanced biomedical research applications, including investigation of the unfolded protein response (UPR) and ER stress signaling in ovarian cancer.
The A2780 host cell line is derived from a patient with ovarian adenocarcinoma and serves as a well-characterized model for ovarian cancer biology, particularly in studies of cisplatin sensitivity and chemoresistance. These epithelial cells display robust growth and a defined sensitivity to platinum-based therapeutics, making them a valuable tool for dissecting drug sensitivity mechanisms. The A2780 background has been extensively employed to unravel pathways governing acquired and intrinsic drug resistance, and it offers a clinically relevant platform for functional genomics of cancer cell stress responses.
DNAJC3 encodes an endoplasmic reticulum (ER)-resident co-chaperone that acts as a negative regulator of the PERK (EIF2AK3) arm of the UPR. The protein interacts with key stress-sensing components, including HSPA5 (BiP), PERK, and IRE1??, and its regulatory activity is influenced by upstream UPR mediators ATF6 and XBP1. Under basal conditions, DNAJC3 suppresses PERK kinase activity; upon ER stress, such as treatment with thapsigargin or tunicamycin, its inhibition is relieved. Loss of DNAJC3 enhances PERK autophosphorylation and kinase activity, leading to increased phosphorylation of eIF2??. This, in turn, preferentially upregulates translation of ATF4 and promotes expression of the downstream pro-apoptotic transcription factor CHOP, thereby potentiating the UPR signaling cascade and shifting the cellular fate toward apoptosis under unresolved ER stress.
In the context of A2780 ovarian cancer cells, ablation of DNAJC3 is predicted to sensitize the cells to ER stress-inducing agents, potentially overcoming chemoresistance mechanisms that rely on attenuation of PERK signaling. The knockout model allows researchers to directly assess how dysregulation of the UPR impacts cell viability, apoptotic thresholds, and drug sensitivity. By augmenting the eIF2??-ATF4-CHOP axis, this model provides a powerful system for identifying therapeutic vulnerabilities linked to protein homeostasis and for evaluating strategies that exploit ER stress overload in ovarian cancer.
This DNAJC3 knockout product is suitable for a wide range of experimental applications. It can be used to perform western blotting analysis of PERK, phospho-eIF2??, ATF4, and CHOP; RT-qPCR profiling of UPR target genes; cell viability and apoptosis assays after ER stress induction with tunicamycin or thapsigargin; co-immunoprecipitation of BiP-DNAJC3 complexes; and phospho-signaling analysis. Transcriptomic changes can be explored via RNA-seq, and functional genomics screens can be conducted to identify modulators of PERK-dependent signaling. For detailed product specifications and ordering information, please contact Ascent Research.
