The FKBP15 Knockout Raji Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population derived from the Raji B lymphocyte line. This product enables loss-of-function studies of FKBP15, a key modulator of mTORC1 signaling and autophagy, within a well-characterized Burkitt’s lymphoma background. The heterogeneous knockout pool provides a powerful tool for investigating gene function without the biases of single-cell cloning, making it suitable for population-level phenotypic analyses and drug sensitivity screens.
The parental Raji cell line was established from a male patient with Burkitt’s lymphoma and harbors an Epstein-Barr virus (EBV) genome as well as a t(8;14) translocation that drives constitutive MYC overexpression. These cells retain features of germinal center B lymphocytes and are widely used to study B-cell malignancies, mTOR-dependent growth, and apoptotic pathways. Their rapid proliferation and sensitivity to rapamycin analogues make them an ideal host for dissecting FKBP15??s role in mTOR-regulated metabolism and survival.
FKBP15 encodes a lysosome-associated peptidyl-prolyl isomerase that scaffolds mTORC1 signaling by interacting with the Raptor, Rag GTPases, and the GATOR complex downstream of amino acid and growth factor inputs. Under nutrient-replete conditions, FKBP15 facilitates mTORC1 recruitment and activation at the lysosomal surface, promoting phosphorylation of downstream effectors S6K1 and 4E-BP1 while suppressing the ULK1 autophagy initiation complex and TFEB-dependent lysosomal gene expression. Disruption of FKBP15 uncouples mTORC1 from lysosomal nutrient sensing, leading to diminished S6K1/4E-BP1 signaling and induction of autophagy, even in the presence of amino acids or growth factors. This molecular network intersects with the TSC1/TSC2-Rheb axis and AMPK energy-sensing pathways, positioning FKBP15 as a central integrator of anabolic and catabolic signals.
Within the Raji lymphoma context, FKBP15 knockout is expected to rewire mTORC1-driven anabolic programs that are exacerbated by MYC overexpression and EBV latency proteins. Loss of FKBP15 may attenuate rapamycin-hypersensitive proliferation and alter the balance between protein synthesis and autophagic recycling??processes critical for lymphoma cell survival under nutrient stress. This model enables direct interrogation of FKBP15??s contribution to mTOR-dependent growth control and its potential synthetic lethal interactions with MYC or other oncogenic drivers in aggressive B-cell malignancies.
Researchers can employ this polyclonal knockout population in Western blot analysis of mTORC1 substrate phosphorylation (S6K1, 4E-BP1), autophagy flux assays monitoring LC3 lipidation and p62 turnover, cell proliferation and viability measurements, flow cytometry-based cell cycle profiling, and dose-response studies with rapamycin or mTOR kinase inhibitors. The model is suited for investigations into lymphoma biology, mTOR signaling, autophagy regulation, cancer metabolism, and drug sensitivity screening. For further information, please contact Ascent Research.
