The DUSP1 Knockout HAP1 Polyclonal Cells provide a CRISPR/Cas9-edited polyclonal knockout model for studying DUSP1 in human hematopoietic cells. The polyclonal population encompasses diverse gene disruptions, reducing clonal bias and enabling robust functional analyses of DUSP1-dependent signaling.
HAP1 cells are a near-haploid human adherent line derived from the KBM-7 chronic myeloid leukemia (CML) isolate. The near-haploid genome simplifies genetic manipulation and facilitates clear genotype-phenotype relationships, while the CML background supplies a disease-relevant platform for examining phosphatase-mediated control of oncogenic signaling.
DUSP1 encodes an inducible dual-specificity phosphatase that negatively regulates MAP kinase cascades by dephosphorylating phosphothreonine and phosphotyrosine on activated ERK1/2 (MAPK3/1), JNK1/2 (MAPK8/9), and p38??/?? (MAPK14/11). Its expression is rapidly induced by growth factors (e.g., EGF, PDGF), pro-inflammatory cytokines (TNF??, IL-1??), and stress signals (oxidative stress, UV radiation, LPS). The phosphatase directly interacts with MAPK1/ERK2, MAPK8/JNK1, and MAPK14/p38??, blocking their activity and preventing phosphorylation of downstream transcription factors such as c-FOS, c-JUN, and ATF2. Thus, DUSP1 serves as a critical feedback regulator of the RAS/RAF/MEK/ERK, ASK1/MKK4/JNK, and MKK3/6/p38 cascades, shaping the magnitude and duration of MAPK-driven gene expression and cellular responses.
In HAP1 CML cells, DUSP1 knockout removes a key brake on MAPK signaling that is typically co-opted by BCR-ABL1, allowing investigation of hyperactive ERK, JNK, or p38 pathways. The polyclonal near-haploid population ensures that disruptive edits yield profound loss-of-function effects, making this model ideal for dissecting oncogene-phosphatase interactions and for identifying synthetic lethal dependencies. This system is particularly useful for studying how leukemic cells manage stress and mitogenic signals and for screening compounds that exploit the heightened MAPK activity caused by DUSP1 loss.
These DUSP1 knockout cells support a range of applications: western blotting for phospho-MAPKs, RT-qPCR validation, proliferation and apoptosis assays (e.g., Annexin V staining), MAPK reporter assays, cell cycle flow cytometry, and transcriptomic profiling by RNA-seq. Key research areas include cancer signaling, chemoresistance mechanisms, stress response, and inflammatory pathway analysis. For additional technical details, lot-specific validation data, or ordering assistance, please contact Ascent Research.
