The EIF2AK3 Knockout MES-OV Polyclonal Cells consist of a CRISPR/Cas9-edited polyclonal population with targeted disruption of the EIF2AK3 gene, which encodes the ER stress sensor kinase PERK, in the MES-OV human ovarian surface epithelial cell line. This polyclonal knockout model provides a genetically diverse loss-of-function system, eliminating PERK activity across the population without selection of individual clones.
MES-OV is an immortalized line derived from normal human ovarian surface epithelium, the monolayer that envelops the ovary and is considered a cell-of-origin for ovarian carcinomas. These cells maintain epithelial characteristics and are widely used to study ovarian biology, stress responses, and early transformation events.
PERK (EIF2AK3) is a type I ER transmembrane kinase that serves as a critical sensor of ER stress. In unstressed cells, PERK is kept inactive by association with BiP (HSPA5); upon accumulation of misfolded proteins, BiP dissociates, allowing PERK autophosphorylation and activation. Active PERK phosphorylates eIF2?? (EIF2S1) at Ser51, inhibiting global translation while selectively promoting ATF4 translation. ATF4 then drives expression of adaptive genes, including the transcription factor CHOP (DDIT3) and the regulatory subunit GADD34 (PPP1R15A), which feedback-dephosphorylates eIF2??. PERK also interacts with NRF2 (NFE2L2) and TRAF2 to coordinate antioxidant responses and apoptosis signaling. Under chronic stress, CHOP upregulates pro-apoptotic BCL2 family members, tipping the balance toward cell death. The PERK?CeIF2???CATF4?CCHOP axis is a central arm of the unfolded protein response (UPR) and integrates inputs from IRE1 and ATF6.
In ovarian surface epithelial cells, PERK signaling is poised to govern responses to microenvironmental stresses such as hormonal fluctuations, oxidative stress, and inflammatory cytokines. Aberrant UPR activation and PERK-mediated translation control have been implicated in ovarian cancer malignancy, chemoresistance, and metabolic disorders like diabetes and Wolcott-Rallison syndrome. Disruption of EIF2AK3 in the MES-OV background enables dissection of PERK-dependent stress adaptation and survival pathways underlying ovarian carcinogenesis.
Researchers can employ this polyclonal knockout model to examine ER stress signaling dynamics following treatment with tunicamycin, thapsigargin, or hypoxia. Standard assays include western blotting for phosphorylated PERK and eIF2??, RT-qPCR for ATF4 and CHOP, apoptosis detection via caspase activity or annexin V binding, and ATF4 luciferase reporter analysis. The model is also suitable for functional genomics screens and studies of drug resistance mechanisms linked to PERK. For additional product information, please contact Ascent Research.
