The DNAJC10 Knockout Jurkat Polyclonal Cells represent a human T-lymphocyte-based product featuring a CRISPR/Cas9-edited polyclonal knockout cell population with targeted disruption of the DNAJC10 gene. This loss-of-function model is engineered in the Jurkat host cell background to enable investigations into endoplasmic reticulum (ER) proteostasis and stress signaling. Because the product comprises a polyclonal population, it retains the heterogeneity inherent to CRISPR/Cas9-mediated gene editing, providing a physiologically relevant system for studying DNAJC10-dependent processes without the homogeneity of single-cell clones.
The Jurkat cell line is an immortalized human T lymphocyte derived from an acute T-cell leukemia patient and serves as a well-established model for T-cell signaling, leukemia biology, and apoptosis. Its leukemic origin makes it particularly valuable for dissecting oncogenic signaling and drug resistance mechanisms. In the context of ER stress research, Jurkat cells offer a robust platform to examine how malignant hematopoietic cells handle protein-folding stress, as they exhibit active secretory pathways and heightened sensitivity to perturbations in ER function.
DNAJC10 encodes an ER luminal cochaperone and protein disulfide isomerase that functions in the ER-associated degradation (ERAD) and unfolded protein response (UPR) pathways. Mechanistically, DNAJC10 facilitates the retrotranslocation and proteasomal degradation of misfolded proteins, thereby maintaining ER proteostasis. It operates within a network of interacting factors including HSPA5 (BiP), EDEM1, and PDIA6. Upstream regulators that activate DNAJC10 expression and UPR signaling are ER stress inducers such as tunicamycin, along with XBP1 splicing and ATF6 activation. Downstream consequences of proper DNAJC10 function include reduced ER stress and enhanced clearance of aberrant proteins, while its disruption leads to accumulation of ERAD substrates and heightened sensitivity to ER stress.
In Jurkat cells, DNAJC10 knockout permits detailed examination of ER proteostasis control in a leukemic background, offering insights into how cancer cells survive proteotoxic insults. This model is particularly relevant for studying leukemia drug resistance, as ER stress pathways are frequently activated in response to chemotherapeutics. Additionally, it provides a system to explore the interplay between ER stress and apoptotic signaling, and to identify vulnerabilities that can be therapeutically targeted in T-cell malignancies and other ER stress-related disorders, such as neurodegenerative diseases.
Typical research applications include Western blot analysis of UPR markers (e.g., BiP, CHOP), RT-qPCR profiling of ER stress-responsive genes, and flow cytometric assessment of apoptosis using Annexin V staining. Immunofluorescence can be employed to examine ER morphology changes, while co-immunoprecipitation assays enable study of HSPA5 interactions. Functional studies often utilize tunicamycin sensitivity and proteasome inhibition assays to evaluate ERAD capacity and stress responses. For more information, please contact Ascent Research.
