The BAG6 Knockout Jurkat Polyclonal Cells represent a CRISPR/Cas9-edited polyclonal cell population in which the BAG6 gene has been disrupted, generating a loss-of-function model for functional studies. This product provides a mixed population of Jurkat cells carrying diverse gene-editing events, enabling robust assessment of BAG6-dependent processes without clonal selection artifacts. The knockout is introduced by transient Cas9 and guide RNA delivery, creating a stable polyclonal pool that retains the intrinsic advantages of the host cell background while abrogating BAG6 protein expression. As a tool for investigating diverse signaling and quality-control pathways, these cells are suited for applications requiring a near-physiological genetic knockout in an immortalized T lymphocyte model.
The Jurkat host cell line is an immortalized human T-cell leukemia line derived from an acute T-cell leukemia patient. Jurkat cells express a functional T-cell receptor and are highly sensitive to Fas-mediated apoptosis, making them a gold standard for studying T-cell signaling, programmed cell death, and HIV infection mechanisms. These cells grow in suspension and maintain consistent growth kinetics, ideal for high-throughput screening and reproducible biochemical assays. Their leukemic origin also positions them as a relevant model for hematological malignancies, particularly in the context of p53 signaling and immune evasion.
BAG6 functions as a multifunctional cochaperone with critical roles in protein homeostasis and immune surveillance. It acts as a nucleotide exchange factor for HSP70, promoting substrate release, and facilitates the insertion of tail-anchored proteins into the endoplasmic reticulum membrane via the TRC complex, interacting with GET4 and UBL4A. BAG6 also enhances MHC class I antigen presentation by coordinating with TAP and tapasin, and regulates p53-mediated apoptosis by stabilizing p53 and promoting its acetylation through p300, which influences the expression of pro-apoptotic genes like BAX and MCL-1. Functional partners include HSPA1A, HSP90AA1, STUB1/CHIP, and VCP/p97, linking BAG6 to the ER-associated degradation (ERAD) machinery. Upstream regulators such as TP53 and RNF126 modulate BAG6 activity, converging on processes spanning the unfolded protein response, proteasomal degradation, and apoptotic execution involving caspase-3 activation.
In the Jurkat T-cell context, BAG6 knockout is particularly significant for dissecting the interplay between p53-dependent apoptosis and immune receptor signaling. Jurkat cells harbor wild-type p53, which is often functionally suppressed in many cancers; BAG6 loss may attenuate p53 stabilization and transcriptional output, altering sensitivity to genotoxic stress and ER stressors like tunicamycin or thapsigargin. Additionally, disruption of MHC class I presentation pathways can impair antigen presentation, providing a model for immune evasion studies relevant to viral infection and tumor immunology. By uncoupling BAG6 from its role in tail-anchored protein biogenesis, researchers can explore how protein misfolding triggers ER stress and apoptosis specifically in T-cell leukemia. This model also enables investigation of the BAG6?CHSP70 axis in regulating MCL-1 stability, a key anti-apoptotic factor in lymphocyte survival, and in modulating mitochondrial outer membrane permeabilization via BCL2 family interactions.
These polyclonal knockout cells support a broad range of experimental applications, including investigation of ER protein quality control and the unfolded protein response, screening for chemical modulators of proteostasis and ERAD, and analysis of MHC class I antigen presentation dynamics. The model is amenable to flow cytometry-based measurement of MHC I surface expression and Annexin V/PI apoptosis assays, as well as Western blotting for BAG6, p53, MCL-1, and cleaved caspase-3. Co-immunoprecipitation can be used to assess disrupted HSP70?CBAG6 complex formation, while RT-qPCR readouts of p53 target genes report on transcriptional activity. Drug sensitivity profiling with ER stress inducers or proteasome inhibitors allows elucidation of BAG6-dependent vulnerabilities in leukemic cells. For further information or technical support, please contact Ascent Research.
