BAG3 Knockout Ca Ski Polyclonal Cells represent a CRISPR/Cas9-edited polyclonal knockout cell population derived from the Ca Ski human cervical carcinoma line, engineered to disrupt the BAG3 gene. This polyclonal population provides a genetically heterogeneous loss-of-function model, enabling robust investigation of BAG3-dependent pathways without the bias of clonal selection. By generating a mixed population of edited cells, this product allows for the study of gene disruption effects across a broad cellular context, making it suitable for functional genomics, signaling studies, and phenotypic screening in cervical cancer research.
The host cell line, Ca Ski, is an adherent epithelial-like cell line originally isolated from a cervical squamous cell carcinoma and characterized by stable integration of HPV-16 genomes. It widely serves as a model for HPV-driven oncogenesis, expressing viral oncoproteins E6 and E7 that inactivate tumor suppressors p53 and retinoblastoma protein. Ca Ski cells retain key features of cervical cancer, such as uncontrolled proliferation and resistance to apoptosis, and are employed extensively in studies of tumor biology, drug response, and host-virus interactions.
BAG3 encodes a stress-inducible co-chaperone that operates at the intersection of autophagy and apoptosis. Mechanistically, BAG3 interacts with HSP70 and HSPB8 to facilitate selective autophagic clearance of aggregated proteins through the receptor SQSTM1/p62, while simultaneously binding and stabilizing BCL2 to inhibit caspase-mediated apoptosis. Its expression is upregulated by HSF1, NF-??B, AP-1, STAT3, and EGFR signaling, and it feeds into MAPK and NF-??B pathways. Downstream targets include LC3, filamin A, and NF-??B p65, and BAG3 functionally regulates protein quality control and cell survival networks.
In the context of Ca Ski cells, which rely on HPV oncoproteins for sustained proliferation, BAG3 likely contributes to tumor cell adaptation under proteotoxic stress and chemoresistance. Disruption of BAG3 in this polyclonal knockout population provides a powerful tool to dissect its role in autophagy-mediated survival, apoptosis evasion, and NF-??B-driven transcription specific to HPV-positive cervical carcinoma. This model enables analysis of how BAG3 coordinates with HSP70 and BCL2 to maintain cellular homeostasis and influence drug sensitivity.
Key applications include investigating autophagy mechanisms through LC3-II and SQSTM1/p62 turnover, assessing apoptosis resistance via caspase-3/7 activity assays, and evaluating drug sensitivity (e.g., cisplatin). Co-immunoprecipitation can probe BAG3-HSP70 interactions, while immunofluorescence visualizes autophagosome formation. Cell viability, migration, and invasion assays further characterize functional outcomes. This product supports target validation, resistance studies, and protein quality control research in cancer biology. For further technical details, please contact Ascent Research.
