The DNAJB4 Knockout K-562 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population in which the human DNAJB4 gene has been disrupted to create a loss-of-function model. Unlike monoclonal isolates, this polyclonal pool preserves a broad representation of editing events, enabling the study of heterogeneous cellular responses related to chaperone function. The cells are suitable for researchers investigating proteostasis, stress biology, and cancer cell signaling in a genetically defined knockout background.
The host K-562 cell line is a widely utilized model derived from a 53-year-old female with chronic myelogenous leukemia in blast crisis. It harbors the Philadelphia chromosome encoding the BCR-ABL fusion oncoprotein, which drives constitutive tyrosine kinase activity and promotes leukemic cell proliferation and survival. K-562 cells exhibit multipotent differentiation capacity, particularly along erythroid lineages, and are extensively employed in studies of leukemia biology, erythropoiesis, and oncogenic signal transduction.
DNAJB4 encodes a DnaJ/HSP40 family co-chaperone that partners with the molecular chaperone HSP70 (HSPA1A) to mediate ATP-dependent protein folding, refolding, and targeting of terminally misfolded substrates for degradation. It operates within a network that includes HSP90, other co-chaperones, and ubiquitin ligases, and transcriptionally responds to heat shock factor 1 (HSF1) activation under conditions of heat shock, oxidative stress, and proteotoxic challenge. DNAJB4 contributes to the clearance of aggregation-prone proteins and may modulate the stability of client oncogenic kinases, thereby bridging protein quality control with cellular signaling pathways.
In K-562 leukemia cells, disruption of DNAJB4 is anticipated to compromise the co-chaperone network and impair the cellular capacity to buffer proteotoxic stress. The constant burden of BCR-ABL-driven protein misfolding renders leukemic cells particularly dependent on efficient chaperone systems for survival. Consequently, DNAJB4 knockout may sensitize cells to proteasome inhibition, oxidative damage, or tyrosine kinase inhibitors, offering a platform to dissect stress-response adaptations and to identify therapeutic vulnerabilities.
These polyclonal knockout cells support a variety of functional assays. Western blotting and RT-qPCR can quantify expression of HSP70, HSP90, and stress-responsive genes. Cell viability and apoptosis assays under thermal, oxidative, or pharmacological stress measure the consequences of DNAJB4 loss. Co-immunoprecipitation studies probe altered chaperone-client interactions, while proteasome activity assays evaluate degradation pathway efficiency. Additionally, drug sensitivity testing can determine whether DNAJB4 status modulates responses to BCR-ABL inhibitors or proteasome inhibitors. For further information, please contact Ascent Research.
