The ATF4 Knockout Ca Ski Polyclonal Cells represent a polyclonal knockout cell population generated by CRISPR/Cas9-mediated disruption of the ATF4 gene in the Ca Ski human cervical carcinoma cell line. This product provides a stable loss-of-function model for investigating ATF4-dependent stress signaling and cervical cancer biology. The polyclonal nature ensures representation of diverse editing events, making it suitable for population-level functional studies without clonal artifacts. It enables direct assessment of ATF4’s role in downstream transcriptional programs and phenotypic responses.
Ca Ski cells are an epithelial cell line originating from a cervical epidermoid carcinoma metastasis, harboring an integrated HPV16 genome and expressing E6 and E7 oncoproteins. These cells serve as a central model for HPV-driven cervical carcinogenesis, recapitulating oncogenic transformation and viral?Chost interactions. Their robust growth and adherent properties facilitate diverse functional assays.
ATF4 is a master transcription factor of the integrated stress response (ISR), activated by eIF2?? phosphorylation mediated by kinases such as PERK, GCN2, PKR, and HRI. Once induced, ATF4 transactivates genes including ASNS, SLC7A11, DDIT3 (CHOP), ATG5, ATG7, PPP1R15A (GADD34), and GPX4, coordinating amino acid metabolism, redox balance, autophagy, and apoptosis. ATF4 also interacts with C/EBP??, C/EBP??, CHOP, FOXO, CREB, and ATF3 to modulate transcriptional responses. Prolonged ATF4 activation can drive CHOP-dependent apoptosis, whereas GADD34 induction feeds back to dephosphorylate eIF2??, restoring homeostasis.
In HPV-positive Ca Ski cells, ATF4 likely mediates adaptation to proteotoxic and metabolic stresses imposed by viral oncoprotein expression and the tumor microenvironment. Knockout of ATF4 in this polyclonal model enables dissection of its contributions to cell proliferation, ER stress survival, metabolic rewiring, and chemoresistance to agents such as cisplatin and bortezomib. Such studies can uncover vulnerabilities linked to the ISR in cervical carcinoma and inform combination therapies targeting HPV and stress pathways.
These knockout cells are suitable for western blotting of ATF4, eIF2?? phosphorylation, and CHOP; RT-qPCR of ASNS and SLC7A11; viability and apoptosis assays under tunicamycin-induced ER stress; migration/invasion assays; drug sensitivity screens; and RNA-seq transcriptomic profiling. The model supports mechanistic studies of ISR signaling in cervical cancer and preclinical evaluation of ISR-targeting agents. Please contact Ascent Research for additional information.
