The HM13 Knouckout SK-HEP-1 Polyclonal Cells product is a CRISPR/Cas9-edited polyclonal knockout cell population derived from the SK-HEP-1 cell line. These cells carry a targeted disruption of the HM13 gene, which encodes the signal peptide peptidase (SPP), an ER-resident intramembrane aspartyl protease. The polyclonal composition reflects multiple independent editing events, providing a reliable loss-of-function model for functional genomics studies without the need for clonal isolation. This product is designed to facilitate investigation of HM13/SPP-mediated peptide processing and its downstream biological effects.
SK-HEP-1 is a human liver adenocarcinoma cell line originally isolated from the ascites of a patient with hepatic adenocarcinoma. It is characterized by an endothelial-like morphology and co-expression of epithelial and endothelial markers, making it an exceptional model for studying hepatic endothelial biology, tumor microenvironment interactions, and liver-specific pathologies. The cell line is widely employed in hepatocellular carcinoma, hepatitis C virus infection, and metastasis research, thus offering a clinically relevant context for HM13 functional analysis.
At the molecular level, HM13/SPP is an intramembrane aspartyl protease that cleaves signal peptides released from preproteins. The resulting peptide fragments are loaded onto HLA-E via TAP and tapasin for immune surveillance. HM13 expression is induced by interferon-gamma and ER stress signals (tunicamycin, thapsigargin) through ATF6. SPP activity generates HLA-E?Cpeptide complexes and antigenic fragments, and the protease associates with HLA-A, beta-2 microglobulin, calnexin, and calreticulin, placing HM13 at the intersection of signal peptide processing, ER-associated degradation, and adaptive immunity.
In the SK-HEP-1 background, HM13 knockout is expected to significantly reduce the supply of SPP-generated peptides required for stable HLA-E surface expression, thereby attenuating HLA-E-dependent immune inhibitory signals to NK cells and CD8+ T cells. This disruption provides a powerful tool for dissecting minor histocompatibility antigen presentation and immune evasion mechanisms in liver cancer. The endothelial-like properties of SK-HEP-1 additionally enable exploration of SPP function in hepatic sinusoidal endothelium and angiogenic processes, areas relevant to tumor progression.
Key applications of HM13 knockout SK-HEP-1 polyclonal cells include the study of minor histocompatibility antigen generation, HLA-E-mediated immune escape, signal peptide peptidase biochemistry, and antiviral immune responses during hepatitis C virus infection. The cells are compatible with a wide array of assays, including western blotting, RT-qPCR, flow cytometry, immunofluorescence, HLA-E stabilization assays, and peptide elution coupled with mass spectrometry, allowing quantitative analysis of HM13/SPP-dependent pathways. The polyclonal knockout format ensures robustness and biological variability, making it suitable for high-throughput screening and mechanistic investigations. For further information or custom solutions, please contact Ascent Research.
