The HERPUD2 Knockout SK-HEP-1 Polyclonal Cells represent a CRISPR/Cas9-edited polyclonal knockout cell population derived from the SK-HEP-1 human hepatic endothelial cell line, with targeted disruption of the HERPUD2 gene. This polyclonal pool provides a heterogeneous population of edited cells, enabling the study of HERPUD2 loss-of-function without clonal bias.
SK-HEP-1 is an established cell line originally isolated from the ascitic fluid of a patient with liver adenocarcinoma. Despite its endothelial origin, it displays epithelial morphology and is widely used as a model for hepatocellular carcinoma (HCC). The line retains key features relevant to hepatic pathology and serves as a robust platform for investigating molecular mechanisms in liver cancer.
HERPUD2 encodes an endoplasmic reticulum (ER) stress-inducible protein that participates in the unfolded protein response (UPR) and ER-associated degradation (ERAD). It is transcriptionally upregulated by ATF4 and XBP1s downstream of PERK and IRE1?? signaling, and it interacts with core ERAD components, including HERPUD1, VCP/p97, DERL1, HRD1, and SEL1L, to facilitate clearance of misfolded proteins. Loss of HERPUD2 disrupts this pathway, leading to accumulation of polyubiquitinated protein aggregates, dysregulated ER calcium release, and enhanced CHOP-mediated apoptosis under stress conditions induced by agents such as tunicamycin, thapsigargin, or homocysteine.
In SK-HEP-1 cells, which model HCC, HERPUD2 knockout exacerbates ER stress vulnerability and perturbs calcium homeostasis, making this polyclonal knockout population particularly valuable for cancer biology research. The impaired adaptation to proteotoxic stress may alter sensitivity to therapeutic agents that target the proteasome or ER stress pathways, providing insight into drug response mechanisms. Moreover, the interplay between ERAD dysfunction and apoptotic signaling through caspase activation offers a platform to explore molecular determinants of cell death in hepatic cancer cells.
This product is suited for a broad range of applications, including dissecting UPR/ERAD signaling, evaluating ER stress-induced apoptosis, and conducting calcium flux studies. Researchers can assess pathway activation by western blotting for GRP78 and CHOP, quantify gene expression changes via RT-qPCR for ER stress targets, visualize ER morphology through immunofluorescence, measure apoptosis using flow cytometry (Annexin V/PI), and monitor calcium dynamics with Fluo-4-based assays. Proteasome activity measurements further complement studies of proteostasis. The polyclonal nature supports population-level analyses without clonal artifacts. For additional information, please contact Ascent Research.
