The DNAJA2 Knockout Raji Polyclonal Cells represent a CRISPR/Cas9-edited polyclonal knockout cell population derived from the human Burkitt lymphoma Raji B-cell line. These cells harbor a targeted disruption of the DNAJA2 gene, generated through CRISPR/Cas9-mediated genome editing, resulting in a heterogeneous loss-of-function model suitable for studying co-chaperone biology. As a polyclonal knockout pool, this product preserves the diversity of editing outcomes across the population, enabling robust assessment of DNAJA2-dependent phenotypes without clonal bias. Researchers can employ this model to investigate the consequences of impaired Hsp70 co-chaperone activity in a B-cell malignancy context.
The parental Raji cell line is an immortalized, Epstein-Barr virus (EBV)-positive B lymphocyte line isolated from a Burkitt lymphoma patient. Characterized by a MYC translocation t(8;14), Raji cells exhibit constitutive activation of survival and proliferative pathways, making them a widely used model for B-cell biology, lymphomagenesis, and immune responses. Their EBV-driven transformation and oncogenic MYC overexpression create a stress-prone environment in which protein quality control networks are particularly critical, providing a relevant background for dissecting the role of chaperone systems in lymphoma maintenance.
DNAJA2 encodes a J-domain co-chaperone that directly interacts with and activates the ATPase activity of Hsp70 chaperones, including the stress-inducible HSPA1A and constitutive HSPA8. Through formation of a triage complex with the E3 ubiquitin ligase CHIP (STUB1) and BAG-family nucleotide exchange factors, DNAJA2 facilitates client protein folding, translocation, and when folding fails, proteasomal degradation. This co-chaperone is a key node in the Hsp70 chaperone cycle and is transcriptionally upregulated by HSF1 in response to heat shock, oxidative stress, and endoplasmic reticulum stress. Downstream, DNAJA2 governs the clearance of aggregated proteins and modulates the unfolded protein response (UPR) and ER-associated degradation (ERAD) pathways. Its knockout disrupts the Hsp70-CHIP-proteasome axis, leading to accumulation of misfolded proteins and perturbed proteostasis signaling.
In the Raji lymphoma context, loss of DNAJA2 function is predicted to impair the processing of Hsp70 client proteins that sustain malignant B-cell growth and survival. The heightened proteotoxic stress inherent to MYC-driven lymphomas renders these cells acutely dependent on chaperone networks, making the DNAJA2 knockout model a valuable tool for elucidating vulnerabilities in protein quality control mechanisms. By combining this engineered cell pool with assays for proliferation, apoptosis, and proteasome activity, investigators can dissect how Hsp70 co-chaperone disruption influences oncogenic signaling, stress adaptation, and therapeutic sensitivity in B-cell malignancies.
This polyclonal knockout cell population supports a wide array of experimental applications, including Western blotting to confirm target disruption, RT-qPCR for transcriptional profiling, and functional studies such as cell viability and Annexin V/PI apoptosis assays. Co-immunoprecipitation experiments can be performed to assess altered Hsp70-client interactions, while proteasome activity measurements and drug sensitivity tests provide insights into the pharmacological targeting of the chaperone?Cproteasome network. Researchers can also employ flow cytometry to evaluate phenotypic changes. For further information or to discuss custom gene-editing services, please contact Ascent Research.
