FBXO4 Knockout Raji Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population derived from the Raji human B lymphoblastoid cell line. This product provides a mixed population of cells in which CRISPR/Cas9-mediated disruption of the FBXO4 gene has generated a loss-of-function model, enabling functional studies of the encoded F-box protein 4 in a B-cell context. The polyclonal format is suitable for experiments where population-level knockout effects are assessed, and it avoids clonal selection bias while maintaining the heterogeneity often desired in cancer cell models.
Raji cells are a well-characterized human Burkitt lymphoma-derived B lymphocyte line that is positive for Epstein-Barr virus (EBV). They serve as a widely used model system in immunology and cancer research for investigating B-cell malignancies, immune signaling, and lymphomagenesis. The EBV-positive status of Raji cells adds a layer of relevance for studying viral oncogenesis and host-virus interactions in the context of lymphoproliferative disorders.
FBXO4 functions as the substrate recognition subunit of the SCF (SKP1?CCUL1?CF-box protein) E3 ubiquitin ligase complex, mediating the ubiquitination and subsequent proteasomal degradation of key target proteins. It interacts directly with SKP1, CUL1, and RBX1 to form the core ligase machinery. Among its substrates, FBXO4 targets telomeric repeat binding factor 1 (TRF1) and cyclin D1 for degradation. Upstream, ATM kinase and DNA damage signals regulate complex activity. Loss of FBXO4 leads to stabilization of TRF1 and cyclin D1, promoting telomere dysfunction and uncontrolled cell cycle progression through cyclin D1?CCDK4/6 signaling.
In the Raji B-lymphocyte background, FBXO4 disruption provides a platform to examine how proteasomal turnover of cell cycle and telomere regulators prevents lymphomagenesis. Accumulation of cyclin D1 may drive unchecked proliferation, while elevated TRF1 levels can provoke telomere deprotection and genomic instability, two hallmarks of B-cell lymphoma. This model thus recapitulates aspects of oncogenic transformation driven by aberrant ubiquitin-proteasome activity and enables exploration of tumor suppressor mechanisms mediated by FBXO4.
Applications of these polyclonal knockout cells include dissecting the ubiquitin-proteasome system in B-cell lymphoma, probing telomere maintenance and DNA damage responses, and analyzing cell cycle regulation. They are compatible with western blotting for TRF1 and cyclin D1, RT-qPCR for FBXO4 transcript, flow cytometry for cell cycle distribution, telomere length analysis by qFISH, immunofluorescence detection of ??-H2AX foci, colony formation assays, and drug sensitivity screening for E3 ligase modulators. For technical inquiries, contact Ascent Research.
