IDE Knockout A-549 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout population of the human A-549 lung carcinoma epithelial line, featuring targeted disruption of the IDE gene. This heterogeneous loss-of-function model eliminates insulin-degrading enzyme activity, enabling robust investigation of IDE-dependent peptide clearance and signaling modulation without clonal bias.
The A-549 host cell line is a well-characterized model derived from the lung adenocarcinoma of a 58-year-old male, harboring a KRAS G12S driver mutation. These cells exhibit an adherent epithelial morphology and are extensively utilized to study human lung adenocarcinoma biology, alveolar type II epithelial cell function, and oncogenic KRAS-driven signaling. The A-549 background also supports investigations into metabolic signaling pathways, as these cells exhibit robust insulin receptor expression and downstream effector responses, making them a relevant platform for IDE knockout studies.
Insulin-degrading enzyme (IDE) is a zinc metalloprotease that degrades insulin, glucagon, amyloid-beta, and other peptides, regulating their bioavailability. IDE activity is modulated by insulin, glucose, PPAR??, and oxidative stress through NRF2. It interacts with proteasome subunits, ubiquitin, APP, and HSP70, linking its function to the ubiquitin-proteasome system. Downstream, IDE controls INSR-mediated activation of IRS1 and AKT1 via PI3K, and limits amyloidogenic processing of APP by BACE1 and PSEN1. IDE disruption therefore leads to sustained insulin signaling, amyloid-beta accumulation, and impaired proteasomal degradation, disrupting cellular proteostasis.
In the A-549 adenocarcinoma background, IDE knockout offers an accessible epithelial model to study peptide hormone catabolism and proteostasis. These cells endogenously express INSR, IRS1, and AKT1, facilitating analysis of insulin signaling amplification upon IDE loss. Additionally, A-549 cells harbor functional APP processing machinery, including BACE1 and PSEN1, enabling investigation of amyloid-beta accumulation. The coexisting KRAS G12S mutation further allows exploration of cross-talk between oncogenic and metabolic pathways.
Applications include insulin degradation assays with phospho-AKT readouts, amyloid-beta ELISA, proteasome activity measurements, and RT-qPCR or immunoblotting for IDE confirmation. This polyclonal population is well-suited for pooled screens and dose-response studies in proteostasis research. For further information, please contact Ascent Research.
