DNAJB4 Knockout A-549 Polyclonal Cells consist of a CRISPR/Cas9-edited polyclonal population derived from A-549 human lung adenocarcinoma epithelial cells. This heterogeneous pool carries targeted disruption of the DNAJB4 gene, enabling loss-of-function analysis of this Hsp70 co-chaperone. The polyclonal format provides a practical approach for studying gene function while retaining population-level biological variability, avoiding the limitations of single-cell clones. The product is designed for researchers investigating tumor suppressor mechanisms and chaperone biology in a lung cancer context.
The A-549 host line is a hypotriploid cell line from a 58-year-old Caucasian male with lung adenocarcinoma, exhibiting characteristics of alveolar type II epithelial cells. Widely used in cancer and respiratory virus research, these cells offer a well-characterized background for exploring tumor suppressor pathways. Their p53 wild-type status and established signaling networks make them an ideal platform for dissecting DNAJB4-dependent functions in non-small cell lung cancer.
DNAJB4 functions as an HSP40 co-chaperone that partners with Hsp70 (HSPA1A) to promote ubiquitin-proteasome-mediated degradation of misfolded proteins. It interacts with STUB1 and BAG3 within the Hsp70 cycle, directing clients for proteasomal clearance. Upstream, HSF1 activates DNAJB4 transcription under heat shock and oxidative stress; epigenetic silencing via DNA methylation suppresses expression. Downstream, DNAJB4 modulates p53 stabilization, ERK1/2 phosphorylation, and ??-catenin, connecting to p53, ERK/MAPK, and NF-??B pathways. Loss of DNAJB4 may relieve invasion suppression by disrupting p53 and enhancing ERK signaling.
In A-549 cells, DNAJB4 acts as a tumor suppressor limiting migration and invasion. Knockout ablation of its co-chaperone activity may perturb proteostasis and deregulate oncogenic signaling. The resulting polyclonal model enables direct study of enhanced metastatic potential and altered drug responses in a p53-competent background. This system is particularly valuable for examining the intersection of protein quality control and lung cancer progression.
Applications include tumor suppressor studies, metastasis mechanism dissection, chaperone function investigation, and proteostasis research. The cells support drug sensitivity testing to identify vulnerabilities when DNAJB4 is absent. Representative assays include western blotting, RT-qPCR, migration/invasion assays, apoptosis detection, co-immunoprecipitation, reporter assays, and immunofluorescence. For further technical details, please contact Ascent Research.
