The EDEM3 Knockout K-562 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population with disrupted EDEM3 gene expression, providing a loss-of-function model for studying glycoprotein quality control and ER-associated degradation (ERAD). This heterogeneous K-562 derivative enables functional dissection of EDEM3 without the need for single-cell clones.
The parental K-562 cell line originated from a pleural effusion of a 53-year-old female with Philadelphia chromosome-positive CML in blast crisis. Exhibiting a hematopoietic progenitor-like phenotype, K-562 cells are a well-established leukemia model, suitable for examining proteostatic networks under oncogenic stress.
EDEM3 encodes an ER ??-mannosidase that trims mannose residues from N-glycans on misfolded glycoproteins, generating a signal recognized by lectins OS-9 and XTP3-B. These deliver substrates to the SEL1L-HRD1 E3 ligase complex containing Derlin-1 and the VCP/p97 ATPase, leading to retrotranslocation and proteasomal degradation. The unfolded protein response (UPR) upregulates EDEM3 via IRE1-XBP1, PERK-ATF4, and ATF6 pathways.
In K-562 leukemia cells, EDEM3 knockout can uncover vulnerabilities linked to ERAD and UPR signaling, as cancer cells often rely on heightened proteostasis to withstand proteotoxic stress. Disruption of EDEM3 may sensitize cells to chemotherapeutics or proteasome inhibitors, offering a platform to study synthetic lethality and leukemia cell fitness.
Applications include Western blotting and RT-qPCR for knockout validation, tunicamycin-induced ER stress assays, flow cytometry for misfolded protein substrates, proteasome activity assays, and apoptosis measurements. This model supports screening of proteostasis modulators, substrate identification, and investigation of N-glycan processing in leukemia. Contact Ascent Research for further information.
