The DNAJC7 Knockout AGS Polyclonal Cells product consists of a heterogeneous population of AGS human gastric adenocarcinoma epithelial cells subjected to CRISPR/Cas9-mediated disruption of the DNAJC7 gene. As a polyclonal knockout pool, this model provides a loss-of-function system for investigating DNAJC7-dependent cellular processes without clonal selection, enabling the study of gene disruption effects across a diverse cellular background. DNAJC7 encodes a co-chaperone critical for Hsp70/Hsp90 chaperone cycle coordination, and its disruption abolishes the functional link between these major molecular chaperones, leading to impaired protein folding, maturation, and triage decisions. This product is ideally suited for researchers requiring a physiologically relevant, polyclonal knockout context that avoids artifacts associated with single-cell cloning or extensive passaging.
The host AGS cell line (ATCC CRL-1739) is derived from a 54-year-old female and exhibits an adherent epithelial morphology with wild-type p53 status. These cells are widely used as a model for gastric cancer biology due to their retention of differentiated gastric epithelial features, their ability to form polarized monolayers, and their responsiveness to Helicobacter pylori infection. In addition, AGS cells are employed to study epithelial barrier function, signal transduction underlying gastric carcinogenesis, and the cellular response to genotoxic and proteotoxic stress. The wild-type p53 background makes this line particularly valuable for examining chaperone-dependent regulation of p53 stability and activity, which is often disrupted in gastric tumors.
DNAJC7 (also known as TPR2) functions as a tetratricopeptide repeat domain-containing co-chaperone that simultaneously interacts with Hsp70 and Hsp90, facilitating client protein transfer and processing. It is regulated by heat shock factors (HSF1 and HSF2) in response to cellular stress, including heat shock, oxidative stress, and heavy metal exposure. DNAJC7 modulates the folding and activation of numerous Hsp90 client proteins, such as the glucocorticoid receptor, AKT, RAF, and p53, thereby influencing steroid hormone signaling, MAPK and PI3K/AKT pathways, and apoptosis. Through its partnership with the ubiquitin ligase STUB1/CHIP and protein phosphatase PP5, DNAJC7 also bridges chaperone cycles to the ubiquitin-proteasome system, directing terminally misfolded clients toward degradation.
The knockout of DNAJC7 therefore uncouples chaperone-mediated quality control from protein degradation, causing accumulation of misfolded species and dysregulation of key signaling nodes. In the AGS gastric cancer context, loss of DNAJC7 is expected to severely compromise proteostasis, a pathway frequently altered in gastric malignancies to support rapid proliferation and survival under hostile conditions. The disruption of Hsp70/Hsp90 client processing affects multiple oncogenic and tumor-suppressive pathways: reduced AKT and RAF signaling may suppress growth, while impaired p53 folding and degradation can alter genomic stability and stress responses. Additionally, because Helicobacter pylori infection induces oxidative and proteotoxic stress in gastric epithelial cells, the DNAJC7 knockout model provides a valuable tool for dissecting how pathogen-induced stress intersects with host chaperone networks to influence inflammation, cell survival, and transformation.
The polyclonal nature of the knockout population enables the study of heterogeneous cellular responses, reflecting the diversity of gastric tumor microenvironments. This knockout model supports a wide range of experimental applications, including functional dissection of chaperone?Cco-chaperone networks in gastric cancer, modeling of protein aggregation pathologies (e.g., amyotrophic lateral sclerosis), and investigation of heat shock response regulation. Representative assays include western blotting for DNAJC7 and client proteins, RT-qPCR for HSF1 target genes, immunofluorescence to visualize protein aggregation, cell viability assays under heat shock or proteasome inhibition, co-immunoprecipitation of Hsp70/Hsp90 complexes, proteasome activity measurements, and apoptosis detection via Annexin V staining. The cells are also suited for migration and invasion assays to explore the role of proteostasis in gastric cancer metastasis. For additional information, including detailed culture protocols, validation strategies, and pricing, please contact Ascent Research.
