The DUSP15 Knockout HAP1 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population derived from the HAP1 human near-haploid myeloid leukemia-derived cell line. This product features targeted disruption of the DUSP15 gene, encoding a dual-specificity phosphatase that negatively regulates stress-activated MAPK pathways, specifically the JNK and p38 cascades. The polyclonal pool comprises a mixed population of edited cells, providing a heterogeneous loss-of-function model suited for rapid functional studies without single-cell cloning.
HAP1 is a near-haploid, adherent cell line originating from the KBM-7 chronic myeloid leukemia line. With a near-haploid karyotype (except for portions of chromosomes 9 and 22), it simplifies genetic analysis and is widely used in functional genomics screens, including CRISPR-based knockout approaches. Its hematopoietic origin and leukemic background make it relevant for investigating oncogenic signaling, drug resistance, and stress responses in blood cancers, providing a suitable context for studying DUSP15 function.
DUSP15 acts as a negative feedback regulator of JNK and p38 MAP kinases. Following stress stimuli such as UV, osmotic shock, or TNF-alpha, MAP3Ks ASK1 and MEKK1 activate MAP2Ks MKK4/7 and MKK3/6, which phosphorylate JNK1/2 and p38 alpha. These kinases then phosphorylate transcription factors c-Jun and ATF2, driving AP-1-mediated gene expression. DUSP15 dephosphorylates JNK and p38, attenuating signal transduction. Knockout of DUSP15 removes this inhibitory constraint, resulting in sustained phosphorylation of JNK, p38, c-Jun, and ATF2, and enhanced transcriptional responses that can alter proliferation, apoptosis, and stress adaptation.
In the HAP1 context, DUSP15 loss-of-function offers insights into MAPK dysregulation in myeloid leukemia. The near-haploid genome enables clear genotype-phenotype correlation, and the polyclonal population reflects heterogeneous editing, mimicking disease-relevant perturbation. Researchers can examine how persistent JNK/p38 signaling affects leukemic cell viability, chemosensitivity, or kinase inhibitor response, supporting target validation and drug discovery efforts.
Applications include western blotting for phospho-JNK/p38, RT-qPCR for downstream targets, and functional assays such as proliferation, apoptosis, and AP-1 reporter analyses. Stress challenges with UV or anisomycin combined with phospho-flow cytometry quantify pathway kinetics. The knockout pool is suited for drug screening against the JNK/p38 pathway and genome-wide modifier screens. For further information or custom services, please contact Ascent Research.
