The DUSP7 Knockout HAP1 Polyclonal Cells represent a CRISPR/Cas9-edited polyclonal knockout cell population derived from the near-haploid human HAP1 cell line. In this model, the DUSP7 gene has been disrupted via CRISPR/Cas9-mediated gene targeting, generating a heterogeneous pool of cells carrying loss-of-function alleles. This product provides a versatile tool for investigating DUSP7 function in a human cell context without clonal selection, preserving population-level heterogeneity for robust functional studies.
The HAP1 cell line is a near-haploid human fibroblast-like line established from a chronic myelogenous leukemia (CML) patient. These cells express the BCR-ABL fusion oncoprotein, which drives constitutive activation of multiple signaling cascades, including the RAS/RAF/MEK/ERK pathway. Their near-haploid karyotype minimizes genetic redundancy, making HAP1 cells an ideal platform for loss-of-function screens and detailed signaling analysis. The DUSP7 knockout in this leukemic background offers a unique system to dissect feedback mechanisms within oncogenic MAPK signaling.
DUSP7 encodes a dual specificity phosphatase that dephosphorylates and inactivates the MAP kinases ERK1 and ERK2 (MAPK3/1), functioning as a critical negative feedback regulator of the MAPK/ERK cascade. It is activated downstream of growth factor receptors such as EGFR and FGFR via the RAS-RAF-MEK-ERK signaling axis. DUSP7 directly interacts with ERK1/2 and scaffold proteins KSR1 and IQGAP1, positioning it in proximity to activated ERK. By attenuating ERK1/2 phosphorylation, DUSP7 reduces the activity of downstream transcription factors ELK1, c-FOS, c-JUN, and c-MYC, thereby modulating cellular processes such as proliferation, differentiation, and stress responses.
In the HAP1 background, constitutive BCR-ABL signaling potently activates the MAPK pathway, making these cells highly sensitive to disruptions in ERK regulatory mechanisms. Knockout of DUSP7 removes a key brake on MAPK signaling, likely resulting in sustained ERK phosphorylation and enhanced transcription of immediate-early genes. This model allows researchers to study how loss of negative feedback reshapes oncogenic signaling networks and contributes to altered proliferation or drug responses. The haploid state simplifies genetic manipulation and facilitates high-throughput functional genomics, enabling systematic dissection of DUSP7-dependent signaling nodes.
This polyclonal DUSP7 knockout cell pool is suitable for a range of downstream applications. Signaling dynamics can be assessed by measuring ERK phosphorylation via Western blotting or immunofluorescence following growth factor stimulation, and immediate-early gene expression (e.g., c-FOS) can be quantified by RT-qPCR. In cancer research, the cells can be employed in inhibitor dose-response studies to evaluate sensitization or resistance to MEK or RAF inhibitors. Proliferation and cell cycle changes can be monitored via EdU incorporation or flow cytometry. Additionally, the near-haploid genome facilitates pooled CRISPR screens to identify synthetic lethal interactions or modifiers of DUSP7 function. For further information regarding this product, please contact Ascent Research.
