The DNAJC1 Knockout K-562 Polyclonal Cells represent a CRISPR/Cas9-edited polyclonal knockout cell population in which the DNAJC1 gene has been disrupted to generate a loss-of-function model. This product comprises a heterogeneous pool of K-562 cells carrying targeted DNAJC1 disruptions, and it is intended for studying endoplasmic reticulum (ER) proteostasis and stress signaling without clonal selection. The polyclonal format retains population-level diversity, enabling robust assessment of gene function under varied genetic backgrounds.
The host cell line, K-562, was established from the pleural effusion of a patient with chronic myelogenous leukemia in blast crisis. These suspension cells are Philadelphia chromosome-positive and harbor the BCR-ABL1 fusion gene, which drives constitutive tyrosine kinase activity and aberrant hematopoietic differentiation. K-562 serves as a well-characterized model for myeloid leukemia and erythroid/megakaryocytic lineage commitment, providing a disease-relevant context for investigating stress response pathways.
DNAJC1 encodes the ER-resident cochaperone ERdj1, which directly interacts with the major ER chaperone BiP (HSPA5). ERdj1 facilitates co-translational translocation of nascent polypeptides and supports productive folding by recruiting BiP to the translocon. Knockout of DNAJC1 compromises BiP-mediated quality control, leading to accumulation of misfolded secretory and membrane proteins. This triggers the unfolded protein response (UPR) through activation of the sensors IRE1, PERK, and ATF6, which propagate signals via downstream effectors such as XBP1, CHOP, and ATF4. Additional interacting factors include HSP90B1 (GRP94) and lectin chaperones, highlighting the gene??s central role in ER proteostasis networks.
Within the K-562 leukemic background, DNAJC1 knockout provides a unique platform to dissect the intersection of oncogenic stress and ER homeostasis. BCR-ABL signaling imposes high secretory demands on the ER, and proteotoxic stress commonly sensitizes leukemia cells to apoptosis. By disrupting a key cochaperone, this model enables mechanistic studies of how leukemic cells cope with or succumb to ER stress, with implications for understanding protein misfolding disorders, cancer progression, and neurodegeneration.
This knockout cell population is suitable for a wide range of functional assays, including western blotting for DNAJC1 and BiP expression, RT-qPCR profiling of UPR markers (e.g., CHOP, XBP1s), flow cytometric measurement of apoptosis following ER stress induction, and co-immunoprecipitation to assess BiP?Csubstrate interactions. Researchers can apply thapsigargin or tunicamycin to chemically induce ER stress and investigate altered UPR dynamics, or perform high-throughput drug screening for modulators of proteostasis. Cell viability and differentiation studies further extend utility in leukemia biology with an ER stress context. For further technical details, please contact Ascent Research.
