The EIF2A Knockout AGS Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population in which the EIF2A gene is disrupted. This product provides a heterogeneous pool of AGS human gastric adenocarcinoma epithelial cells carrying loss-of-function edits, enabling robust investigation of EIF2A-dependent processes without clonal isolation.
AGS cells are an established model of gastric adenocarcinoma, retaining epithelial characteristics and tumorigenic properties. They are widely employed to study gastric cancer biology, drug responses, and stress adaptation mechanisms relevant to tumor survival in the microenvironment.
EIF2A encodes eIF2??, the regulatory subunit of the eukaryotic initiation factor 2 complex. eIF2?? is a central mediator of the integrated stress response (ISR). Upon diverse stresses, kinases EIF2AK3 (PERK)/ER stress, EIF2AK4 (GCN2)/amino acid deprivation, EIF2AK2 (PKR)/viral dsRNA, and EIF2AK1 (HRI)/heme deficiency phosphorylate eIF2?? at Ser51. This phosphorylation inhibits the guanine nucleotide exchange factor eIF2B, causing global protein synthesis attenuation while enhancing translation of select mRNAs with upstream ORFs, notably ATF4. ATF4 induces DDIT3 (CHOP) and PPP1R15A (GADD34), which feed back to dephosphorylate eIF2??. eIF2?? interacts with eIF2S2 (??), eIF2S3 (??), eIF5, and ribosomes. Thus, EIF2A orchestrates translational reprogramming in response to cellular stress.
Elimination of EIF2A in AGS cells disrupts the ISR, allowing dissection of how eIF2??-mediated translation control affects gastric cancer cell growth, apoptosis, and adaptation to microenvironmental stresses such as nutrient deprivation and chemotherapy. The polyclonal knockout population reflects genetic heterogeneity found in tumors, strengthening the translational relevance of stress response studies.
Applications include investigating ISR signaling in gastric adenocarcinoma, validating translational control targets, and screening modulators of eIF2?? phosphorylation. Representative assays include western blot for phospho-eIF2??, RT-qPCR for ATF4 and CHOP, tunicamycin-induced ER stress tests, polysome profiling, cell viability under stress, and ATF4-luciferase reporters. For further information, contact Ascent Research.