A CRISPR/Cas9-edited polyclonal knockout cell population targeting the DNAJA2 gene in the MES-OV human ovarian endometrioid carcinoma cell line is provided as a ready-to-use loss-of-function model. The product consists of a heterogeneous pool of cells harboring CRISPR/Cas9-mediated disruptions in the DNAJA2 locus, enabling robust functional studies without clonal selection bias. This polyclonal format preserves genetic diversity while ensuring effective reduction of DNAJA2 expression. Researchers can immediately employ these cells in experiments examining the roles of co-chaperone-mediated proteostasis in cancer and stress biology.
The host cell line, MES-OV (JCRB1105), originates from an ovarian endometrioid carcinoma and serves as a clinically relevant model for this subtype of epithelial ovarian cancer. MES-OV cells exhibit characteristic features of endometrioid histology and retain signaling networks typical of ovarian carcinomas, including active oncogenic pathways. This background makes them suited for investigating how proteostasis regulators like DNAJA2 influence tumor cell fitness, drug response, and stress adaptation. The knockout model thus integrates cancer-specific contexts with molecular chaperone biology.
DNAJA2 encodes a J-domain co-chaperone that recruits Hsp70 family members, particularly HSPA1A and HSPA8, to client proteins for folding, trafficking, or degradation. It functions in complexes with co-factors such as BAG3, STUB1/CHIP, HSP90, and HOP/STIP1, directing clients toward the ubiquitin-proteasome system or chaperone-mediated autophagy. DNAJA2 is transcriptionally regulated by HSF1 and the unfolded protein response sensors PERK, IRE1, and ATF6, linking it to cellular stress pathways. DNAJA2 loss impairs Hsp70-dependent quality control, leading to misfolded protein accumulation and activation of stress responses.
In the ovarian endometrioid carcinoma context, DNAJA2 knockout alters the proteostasis network, potentially sensitizing cells to proteotoxic stress and chemotherapeutics that target protein homeostasis. The model enables examination of how cancer cells cope with enhanced misfolded protein burden and may reveal vulnerabilities dependent on Hsp70 co-chaperone activity. Because DNAJA2 interfaces with oncogenic signaling and stress-adaptive programs, this knockout system facilitates studies into the interplay between malignant transformation and chaperone function.
Applications include functional genomics screening to map DNAJA2-dependent pathways, proteostasis assays measuring aggregation and degradation rates, and drug screening for modulators of Hsp70-co-chaperone interactions. Representative experimental readouts are real-time PCR, Western blotting for chaperone and UPR markers, immunofluorescence localization of misfolded proteins, proteasome activity measurements, co-immunoprecipitation of Hsp70 complexes, and flow cytometric analysis of cell viability under proteotoxic challenges such as heat shock or inhibitors. For additional technical details or customized inquiries, please contact Ascent Research.
