The MVP Knockout Raji Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population derived from human Raji B lymphocytes, designed for loss-of-function studies of the major vault protein (MVP). Transient expression of Cas9 nuclease and guide RNA generates heterogeneous MVP disruptions across the pool, preserving biological variability and avoiding clonal selection bias. This polyclonal format provides a ready-to-use model for investigating MVP-mediated cellular processes in lymphoma biology.
The parental Raji cell line is an Epstein-Barr virus (EBV)-positive B lymphoblastoid line isolated from a Burkitt??s lymphoma patient. Raji cells recapitulate key features of B-cell malignancies, including constitutive activation of PI3K/Akt and NF-??B survival pathways, and serve as a well-established model for studying humoral immunity, lymphomagenesis, and drug resistance.
MVP encodes the major vault protein, the main structural component of vault ribonucleoprotein particles that conduct nucleocytoplasmic transport, drug sequestration, and intracellular signaling. MVP expression is transcriptionally regulated by NF-??B, STAT3 (downstream of IL-6), p53, HIF-1??, and growth factor receptors including EGFR, with further modulation through PI3K/Akt and MAPK/ERK cascades. At the functional level, MVP scaffolds an interactome that includes PTEN, SHP-2 (PTPN11), ERK1/2, vPARP, TEP1, and vault RNAs, thereby integrating inputs to control Akt phosphorylation, ERK1/2 activation, SHP-2 phosphatase activity, Bcl-2 expression, and ABC transporter levels. Disruption of MVP by CRISPR/Cas9 attenuates downstream PI3K/Akt/mTOR, MAPK/ERK, NF-??B, and JAK/STAT pathway effectors.
In Raji B lymphoma cells, MVP knockout is particularly significant because these cells depend on heightened PI3K/Akt and MAPK/ERK signaling for proliferation and survival. Loss of MVP impairs Akt and ERK1/2 phosphorylation, reduces Bcl-2 and NF-??B activity, and sensitizes cells to apoptosis. Additionally, ablation of vault-mediated drug sequestration likely increases intracellular drug accumulation, countering the multidrug resistance phenotype prevalent in aggressive lymphomas. This model thus permits dissection of MVP-dependent oncogenic networks in Burkitt??s lymphoma.
Key applications include investigation of vault biology, multidrug resistance mechanisms, and PI3K/Akt/mTOR and MAPK/ERK pathway crosstalk, as well as therapeutic target validation in B-cell lymphoma. The polyclonal knockout cells are compatible with Western blotting for phospho-Akt and phospho-ERK1/2, RT-qPCR for downstream effectors, immunofluorescence, flow cytometry-based drug accumulation assays, apoptosis and proliferation analyses, co-immunoprecipitation, and RNA-seq transcriptomics. These tools support high-throughput drug screening for agents that overcome chemoresistance in MVP-dependent malignancies. For further information, please contact Ascent Research.
