The DNAJB14 Knockout 786-O Polyclonal Cells are a CRISPR/Cas9-edited polyclonal population of 786-O renal adenocarcinoma cells with targeted disruption of the DNAJB14 gene. This heterogeneous knockout pool provides a loss-of-function model that preserves genetic diversity and avoids clonal selection artifacts, suitable for functional studies of DNAJB14 in a bulk cell context.
The 786-O cell line is an epithelial model of clear cell renal cell carcinoma (ccRCC) derived from a primary kidney adenocarcinoma of a 58-year-old Caucasian male. Widely used in ccRCC research, these cells exhibit hallmark dysregulated hypoxia and metabolic pathways, offering a relevant background for exploring tumor biology.
DNAJB14 is a J-domain co-chaperone that interacts with HSP70 family members (HSPA1A, HSPA8) to assist protein folding and target misfolded proteins for ubiquitin-proteasome degradation. Its expression is upregulated by heat shock, ER stress, and the unfolded protein response, and it functions in complex with ubiquitin ligases and BAG family co-chaperones to mediate ER-associated degradation (ERAD). Knockout of DNAJB14 disrupts these proteostasis mechanisms, leading to client protein accumulation and stress pathway activation.
In ccRCC, proteotoxic stress is elevated due to metabolic dysregulation; thus, DNAJB14 loss can exacerbate misfolded protein burden and ER stress, potentially altering tumor cell viability and drug sensitivity. This knockout model enables dissection of co-chaperone-dependent survival mechanisms and identification of vulnerabilities in renal cancer cells.
Applications include proteostasis profiling, ER stress signaling analysis, and drug sensitivity screening using techniques such as western blotting, RT-qPCR, immunofluorescence, proteasome activity assays, and cell viability assays. The polyclonal format is advantageous for high-throughput studies and pooled phenotypic screens. For further technical information, please contact Ascent Research.