The CITED2 Knockout Raji Polyclonal Cells product comprises a CRISPR/Cas9-edited polyclonal population derived from the Raji B lymphocyte line, engineered to ablate CITED2 expression. This loss-of-function model provides a powerful tool for dissecting the transcriptional coactivator activity of CITED2, which bridges key transcription factors to the CBP/p300 coactivator complex. The polyclonal nature of the knockout population captures a range of gene-disruption events, enabling the study of pathway heterogeneity relevant to lymphoma cell biology.
The Raji host cell line is an EBV-positive lymphoblastoid line established from a Burkitt lymphoma patient. Retaining hallmarks of mature B cells, Raji cells express surface immunoglobulins and antigen-presentation molecules, and are widely used to model B-cell lymphomagenesis, immune signaling, and drug responses. This background is particularly suited for examining the role of CITED2 in the interplay between viral oncogenesis and host transcriptional programs, as EBV-driven signaling pathways often converge on transcription factors that engage CITED2.
CITED2 functions as a transcriptional coactivator that physically interacts with CBP (CREBBP) and p300 (EP300), facilitating gene regulation downstream of multiple signaling cascades. Under hypoxic conditions, HIF1A binds CITED2 to promote transcription of VEGFA, EPO, and MMP9. In the TGF-?? pathway, CITED2 complexes with SMAD2 and SMAD3 to modulate CDKN1A and BCL2 expression, while Notch1 intracellular domain also recruits CITED2 for target gene activation. Additionally, CITED2 integrates Wnt/??-catenin signals from Wnt3a and NF-??B stimulation, influencing CCND1 and BAX, thereby forming a nexus for pathways governing proliferation, apoptosis, and differentiation.
In the Raji lymphoma context, CITED2 disruption perturbs the balance of downstream effectors such as CCND1, BCL2, and BAX, altering cell cycle progression and survival. This makes the knockout cells a valuable model for exploring how hypoxia and TGF-??/Notch crosstalk contribute to lymphomagenesis and drug sensitivity. The polyclonal format more faithfully represents the mutational diversity encountered in tumor populations, enhancing the translational relevance of studies on pathway dependencies and adaptive resistance mechanisms.
Typical applications include mapping CITED2-dependent transcriptional networks via RNA-seq, validating protein interactions with CBP/p300 by co-immunoprecipitation, and assessing functional outcomes through MTT/BrdU proliferation assays and Annexin V/PI apoptosis assays. Hypoxia-responsive luciferase reporters and flow cytometric cell cycle analysis can further delineate CITED2??s role in stress responses. The model is also conducive to screening for modulators that restore sensitivity to agents like etoposide or doxorubicin. For further details or custom experimental design, please contact Ascent Research.
