The DAB2IP Knockout Raji Polyclonal Cells are a CRISPR/Cas9-edited polyclonal population derived from Raji B-lymphoblastoid cells, engineered for targeted disruption of the DAB2IP tumor suppressor gene. This loss-of-function model enables pooled analysis of DAB2IP??s regulatory roles in a lymphoma-relevant background while avoiding clonal selection artifacts. The polyclonal format preserves heterogeneous knockout cells that can be used for functional genomics and signaling studies under suspension culture conditions.
Raji is an EBV-positive B lymphoblastoid cell line established from a Burkitt lymphoma patient, characterized by a t(8;14) c-MYC translocation that drives constitutive proliferation. This cell model exhibits constitutive NF-??B activity and survival signaling via the EBV latency III program, making it a standard system for Burkitt lymphoma, B-cell biology, and Epstein-Barr virus research. The well-documented oncogenic background provides a relevant setting for evaluating tumor suppressor disruption.
DAB2IP functions as a negative regulator of multiple oncogenic pathways. Its Ras GAP domain inactivates Ras to suppress ERK1/2 MAPK signaling. As a scaffold, DAB2IP promotes TNF-??-induced apoptosis by binding ASK1 and TRAF2, leading to JNK/p38 activation. It also inhibits NF-??B by recruiting the PP2A catalytic subunit to dephosphorylate IKK. In the Wnt pathway, DAB2IP stabilizes the Axin destruction complex through interactions with GSK3?? and 14-3-3 proteins, downregulating ??-catenin. DAB2IP expression is controlled by FOXO3a, promoter methylation, and miR-92. Key downstream effects involve Ras inactivation, IKK dephosphorylation, NF-??B suppression, JNK/p38 activation, Axin stabilization, and caspase-mediated apoptosis.
Loss of DAB2IP in the Raji background is expected to exacerbate oncogenic signaling, as c-MYC overexpression and EBV latent proteins already stimulate MAPK, NF-??B, and survival pathways. DAB2IP knockout may consequently enhance proliferation, inhibit apoptosis, and dysregulate Wnt/??-catenin activity, potentially recapitulating more aggressive lymphoma features. This model thus offers a pertinent platform for studying cooperative tumor suppressor dysfunction and virus-host signaling interplay in B-cell malignancies.
These polyclonal knockout cells are applicable for tumor suppressor functional studies, pathway profiling, and drug sensitivity screening. Standard assays include Western blotting, RT-qPCR, phospho-ERK immunoblotting, NF-??B luciferase reporter, TOP/FOP Wnt reporter, and Annexin V apoptosis detection. Proliferation (MTT) and migration (Transwell) assays can quantify phenotypic changes. They are suitable for lymphoma drug screening and combination studies. For further information or custom solutions, contact Ascent Research.
