The DNAJC7 Knockout 786-O Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population for loss-of-function studies of the DNAJC7 gene. This product provides a heterogeneous pool of 786-O cells with targeted disruptions in DNAJC7, generated by CRISPR/Cas9-mediated gene editing. The polyclonal format captures a range of knockout alleles, offering a robust model without clonal selection biases. These cells are a versatile tool for probing DNAJC7’s role in chaperone-mediated protein folding and signaling.
The 786-O cell line is an epithelial line derived from a primary clear cell renal cell adenocarcinoma, serving as a model of clear cell renal cell carcinoma (ccRCC). 786-O cells retain key characteristics such as VHL deficiency leading to constitutive HIF pathway activation. This background is clinically relevant for chaperone biology studies in kidney cancer, where proteotoxic stress and aberrant signaling are prominent. The cells are also valuable for drug response studies due to the role of chaperones in therapeutic sensitivity.
DNAJC7 encodes a co-chaperone coordinating client protein transfer from HSP70 to HSP90, a critical step in the HSP90 cycle. This process is essential for folding, maturation, and stability of signaling proteins like AKT, EGFR, and steroid receptors. DNAJC7 interacts with HSP70, HSP90, and the adaptor HOP (STIP1) to facilitate client handoff. Upstream regulators HSF1, proteotoxic stress, and HIF1?? in renal cancer induce chaperone expression. Knockout disrupts this network, causing misfolded client accumulation, impaired HSP90 activity, and altered signaling, providing a powerful mechanistic model.
In 786-O renal carcinoma cells, DNAJC7 loss is significant due to dysregulated proteostasis and high chaperone demand. The VHL-HIF pathway intersects with chaperone expression, as HIF1?? regulates DNAJC7. Client proteins AKT and EGFR, critical for ccRCC proliferation and survival, depend on HSP70-HSP90. Thus, this knockout allows dissection of co-chaperone disruption effects on oncogenic signaling, HSP90 inhibitor sensitivity, and proteotoxic stress responses, potentially revealing therapeutic vulnerabilities.
Researchers can use this polyclonal knockout population for chaperone-mediated protein folding studies, cancer signaling research, and proteostasis investigation. Representative assays include Western blotting for client protein stability (e.g., AKT, EGFR), HSP90 activity assays, co-IP of chaperone complexes, RT-qPCR, proliferation, and apoptosis analyses. Drug resistance mechanisms can be explored via sensitivity to HSP90 inhibitors. The cells are also suitable for studying unfolded protein response dynamics. For product specifications and support, contact Ascent Research.
