The DNAJB11 Knockout K-562 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population derived from the K-562 chronic myeloid leukemia cell line. These polyclonal cells harbor targeted disruptions in the DNAJB11 gene, enabling loss-of-function studies to dissect DNAJB11-dependent endoplasmic reticulum (ER) protein quality control and unfolded protein response (UPR) signaling.
K-562 cells were established from the pleural effusion of a 53-year-old female with chronic myeloid leukemia in blast crisis. They express the BCR-ABL1 fusion oncogene and are p53-deficient, representing a widely used model for leukemia biology, oncogenic signaling, and hematopoietic differentiation. The BCR-ABL1 kinase drives proliferation and survival, and its crosstalk with ER stress pathways is of significant research interest.
DNAJB11 is an ER-resident co-chaperone that partners with BiP (HSPA5) to facilitate protein folding and target misfolded proteins for ER-associated degradation (ERAD). Under ER stress triggered by agents such as tunicamycin or thapsigargin, UPR sensors ATF6, IRE1??, and PERK become activated. IRE1?? catalyzes XBP1 mRNA splicing, producing the active transcription factor XBP1, while PERK-mediated eIF2?? phosphorylation induces ATF4 and CHOP. DNAJB11 is transcriptionally regulated by ATF6 and XBP1 and interacts with ERAD components EDEM1, OS9, SEL1L, and HRD1 as well as the calnexin/calreticulin cycle. Knockout of DNAJB11 disrupts BiP chaperone functions, leading to accumulation of misfolded proteins, chronic ER stress, and sustained UPR activation.
In the K-562 background, DNAJB11 knockout allows interrogation of ER proteostasis in a leukemia context. BCR-ABL1 signaling modulates UPR, and impaired ERAD may alter sensitivity to tyrosine kinase inhibitors like imatinib. This model supports investigation of how chronic ER stress influences apoptosis, drug resistance, and oncogenic signaling, offering insights into potential therapeutic vulnerabilities.
Typical applications include Western blotting for UPR markers (BiP, CHOP), RT-qPCR for XBP1 splicing, immunofluorescence for ER stress markers, flow cytometry for apoptosis, and phospho-signaling analysis of the BCR-ABL pathway. The cells are also suitable for drug sensitivity assays (e.g., imatinib) and UPRE-luciferase reporter assays to monitor UPR activity, making them a versatile tool for ER stress modulator screening and cancer cell biology studies. For further information, please contact Ascent Research.
