The EIF2AK3 Knockout SK-HEP-1 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout population derived from SK-HEP-1, carrying targeted disruption of the EIF2AK3 gene. This heterogeneous loss-of-function model is designed for studying PERK (PKR-like ER kinase) in human hepatic adenocarcinoma cells.
The SK-HEP-1 host cell line was established from ascitic fluid of a patient with liver adenocarcinoma and exhibits mixed epithelial and endothelial features, making it a distinctive model for cancer biology and drug metabolism research. This background supports investigations into hepatocellular carcinoma progression and therapeutic responses.
EIF2AK3 encodes the ER-resident kinase PERK, a key sensor of unfolded protein stress. Under ER stress, PERK dissociates from GRP78/BiP, autophosphorylates, and then phosphorylates eIF2?? (EIF2S1) to attenuate global translation while selectively upregulating ATF4. ATF4 drives transcription of CHOP (DDIT3) and GADD34 (PPP1R15A), shifting the cellular outcome toward apoptosis or adaptive recovery. PERK additionally phosphorylates NRF2 (NFE2L2) to promote antioxidant defenses and interacts with IRE1?? and ATF6 within the UPR network. Upstream activators include glucose deprivation, hypoxia, and oxidative stress.
In the hepatic adenocarcinoma background, PERK disruption provides a powerful means to dissect how cancer cells manage ER stress induced by metabolic imbalances, hypoxia, and chemotherapeutic agents. The PERK?CeIF2???CATF4?CCHOP axis integrates pro-survival and pro-apoptotic signals, and its interruption can reveal critical vulnerabilities, such as increased sensitivity to ER stress-induced apoptosis. This model thus enables targeted investigation of PERK-dependent chemoresistance, autophagy modulation, insulin signaling, and redox homeostasis in liver cancer.
Applications include western blotting and RT-qPCR for UPR markers, ER stress induction by tunicamycin or thapsigargin with viability and apoptosis assays, ATF4/CHOP luciferase reporters, co-immunoprecipitation to map PERK complexes, immunofluorescence, and metabolic assays for insulin signaling. These cells provide a robust tool for screening PERK inhibitors and dissecting integrated stress response pathways. For additional details or to obtain these cells, please contact Ascent Research.
