PDP1 Knockout Raji Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population derived from the Raji B lymphocyte line, providing targeted disruption of the PDP1 gene. This product supplies a heterogeneous pool of edited cells, ideal for examining PDP1 loss-of-function effects in a human Burkitt’s lymphoma background. The knockout is achieved through CRISPR/Cas9-mediated gene disruption, offering a stable model without monoclonality. PDP1 encodes the catalytic subunit of pyruvate dehydrogenase phosphatase, a pivotal enzyme in metabolic transition, and its disruption in polyclonal format enables population-level studies of metabolic adaptation.
Raji cells originated from a patient with Burkitt’s lymphoma and represent an Epstein-Barr virus (EBV)-positive lymphoblastoid cell line that grows in suspension. Widely utilized in immunology and oncology, this B lymphocyte model recapitulates features of germinal center B cells and serves as a platform for investigating B cell biology, lymphoma pathogenesis, and EBV latency. The cell line’s established use in signal transduction and drug discovery makes it a robust host for gene-edited models. Its suspension culture facilitates scalable experimental design for metabolic assays.
PDP1 functions as the catalytic subunit of pyruvate dehydrogenase phosphatase, which dephosphorylates and activates the E1 component (PDHA1) of the pyruvate dehydrogenase complex (PDH). This activation stimulates pyruvate conversion to acetyl-CoA, thereby bridging glycolysis and the tricarboxylic acid (TCA) cycle. PDP1 activity is regulated by insulin and calcium signaling, acting downstream of insulin receptor stimulation and intracellular Ca2+ elevation. The phosphatase interacts with the PDH E2 subunit (DLAT) and the regulatory subunit PDPR, requiring Mg2+ as a cofactor. By opposing pyruvate dehydrogenase kinases (PDKs), PDP1 integrates hormonal signals with metabolic flux. Representative pathway constituents include PDK, PDP1, PDPR, PDHA1, PDHB, DLAT, DLD, acetyl-CoA, NAD+, and FAD.
In the Raji Burkitt’s lymphoma context, metabolic reprogramming toward aerobic glycolysis is a hallmark, and PDP1 knockout offers a means to dissect PDH activation in lymphoma metabolism. Disruption of the phosphatase that reactivates PDH allows investigation of how B lymphomas redirect pyruvate fate and sustain energy demands. This model is pertinent for exploring crosstalk between oncogenic signaling, insulin pathway input, and mitochondrial function in EBV-positive malignancies. Additionally, the link between PDP1 and pyruvate dehydrogenase phosphatase deficiency, congenital lactic acidosis, and neurological disorders positions this model as a tool to study metabolic vulnerabilities in cancer.
These PDP1 knockout polyclonal cells are applicable to diverse metabolic studies, including extracellular flux analysis (Seahorse ECAR/OCR) to assess glycolysis and oxidative phosphorylation. Researchers can employ Western blotting for PDHA1 phosphorylation to validate PDP1 loss and measure pyruvate dehydrogenase activity directly. Lactate production assays, metabolomics, and RT-qPCR for metabolic genes further characterize metabolic rewiring. The model supports drug sensitivity screening with PDH-targeted agents like CPI-613 and flow cytometry for mitochondrial membrane potential. These applications facilitate research into the Warburg effect, insulin signaling, and metabolic adaptation in B-cell malignancies. For further information regarding this knockout cell product, please contact Ascent Research.
