The DUSP5 Knockout HAP1 Polyclonal Cells product provides a CRISPR/Cas9-edited polyclonal knockout cell population for studying the loss of function of the DUSP5 dual specificity phosphatase. This heterogeneous population carries targeted disruptions in the DUSP5 gene, enabling investigation of ERK signaling dynamics and negative feedback regulation. The polyclonal format is well-suited for pooled screening and functional genomics applications where clonal artifacts are minimized.
The host cell line, HAP1, is a haploid human chronic myelogenous leukemia cell line derived from KBM-7. This near-haploid karyotype facilitates CRISPR/Cas9-based knockout screening, as a single mutation event can ablate gene function. HAP1 cells are BCR-ABL positive and retain key oncogenic signaling pathways, making them a valuable model for cancer research and drug discovery.
DUSP5 encodes a nuclear dual-specificity phosphatase that dephosphorylates phosphotyrosine and phosphothreonine residues on ERK1 and ERK2, thereby inactivating the terminal kinases of the RAS-RAF-MEK-ERK cascade. As a critical negative feedback regulator, DUSP5 is transcriptionally induced by ERK1/2 signaling in response to growth factors such as EGF and FGF, as well as oncogenic RAS. This phosphatase modulates downstream transcriptional outputs including ELK1, c-FOS, and cyclin D1, thus controlling cell proliferation and survival.
In the HAP1 cellular context, DUSP5 disruption is expected to perturb the ERK signaling brakes, leading to enhanced and/or sustained MAPK pathway activity. This model enables researchers to dissect the role of DUSP5-mediated negative feedback in leukemic cells and other cancer types, including acute myeloid leukemia, hepatocellular carcinoma, and colorectal cancer. The BCR-ABL-driven background provides a relevant oncogenic setting for evaluating how DUSP5 loss may influence drug sensitivity or resistance mechanisms.
Typical applications of these polyclonal knockout cells include western blotting for ERK phosphorylation, RT-qPCR analysis of DUSP5 and downstream targets, phospho-ERK immunofluorescence, flow cytometry, cell proliferation assays, and phospho-signaling arrays. This product supports functional genomics studies of MAPK/ERK signaling, phosphatase activity, negative feedback in cancer, and CRISPR knockout screening. For additional information or technical support, please contact Ascent Research.
