The DNAJB4 Knockout HAP1 Polyclonal Cells represent a CRISPR/Cas9-edited polyclonal knockout cell population designed for loss-of-function studies of the DNAJB4 gene in a near-haploid human cell background. This product comprises a heterogeneous pool of HAP1 cells carrying targeted disruptions in DNAJB4, generated via CRISPR/Cas9-mediated gene disruption without clonal selection. The polyclonal format retains population-level genetic diversity and is well-suited for pooled functional assays, pathway dissection, and drug response profiling that do not require monoclonal isolation. Researchers can employ this model to investigate the role of DNAJB4 in protein quality control, apoptosis regulation, and stress responses.
The HAP1 host cell line is an adherent, fibroblast-like derivative of the KBM-7 chronic myeloid leukemia line, characterized by a near-haploid karyotype. Its haploid nature simplifies genetic analysis and enhances the penetrance of knockout phenotypes by eliminating complications from second allele compensation. HAP1 cells are widely used for haploid genetic screens and as a model system for leukemia biology. This background provides a robust and reproducible platform for examining DNAJB4 function in a disease-relevant cellular context, particularly for studies linking protein homeostasis to cancer cell survival.
DNAJB4 encodes a co-chaperone that regulates Hsp70 ATPase activity, playing a critical role in protein folding, prevention of aggregation, and targeting of misfolded proteins for degradation. It acts downstream of HSF1 and is induced by heat shock, oxidative stress, and proteasome inhibition. DNAJB4 directly interacts with HSPA1A, HSPA8, and the ubiquitin-proteasome system components STUB1, BAG3, and PSMD2. Through these interactions, DNAJB4 facilitates the delivery of misfolded clients to the proteasome, thereby maintaining proteostasis. Additionally, DNAJB4 modulates apoptosis by influencing BCL2 expression, linking chaperone function to cell death pathways.
In the HAP1 background, DNAJB4 knockout disrupts the chaperone network, leading to accumulation of aggregated proteins and heightened sensitivity to proteotoxic stress. The near-haploid genome ensures that loss-of-function phenotypes are unmasked, making this model especially powerful for probing the relationship between protein quality control and apoptosis in leukemia-derived cells. Given DNAJB4??s involvement in ubiquitin-proteasome-mediated degradation, these knockout cells are valuable for evaluating proteasome inhibitor sensitivity and for dissecting crosstalk between the heat shock response and cell survival signaling. The model also supports studies of BCL2-dependent apoptosis regulation in the context of impaired chaperone activity.
This product is suitable for a broad range of applications, including proteostasis research, cancer drug sensitivity studies, neurodegenerative disease modeling, and heat shock response analysis. Typical downstream assays include western blotting for protein aggregation markers, RT-qPCR for stress gene induction, cell viability assays under proteotoxic conditions, proteasome activity measurements, co-immunoprecipitation of chaperone complexes, immunofluorescence for protein localization, flow cytometry for apoptosis detection, and RNA-seq for transcriptome-wide profiling. For technical specifications, validation data, or ordering information, please contact Ascent Research.
