OBSL1 Knockout Raji Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population derived from the Raji human B lymphocyte line, engineered for loss-of-function studies of the cytoskeletal adaptor protein OBSL1. This polyclonal knockout model provides a heterogeneous pool of cells with targeted disruption of the OBSL1 gene, enabling functional investigation of OBSL1-dependent pathways without clonal selection artifacts. The product is designed to support rigorous interrogation of ubiquitin-mediated growth regulation and IGF-1 signaling in a lymphoma background.
The Raji cell line, established from an EBV-positive Burkitt lymphoma, exhibits lymphoblastoid morphology and expresses characteristic B-cell markers along with MHC class I and II molecules. Widely utilized in immunological and oncological research, Raji cells serve as a robust model for EBV-related lymphomagenesis, B-cell signaling, and tumor biology. Their well-characterized growth properties and signaling networks make them suitable for dissecting the molecular mechanisms governing B-cell malignancies.
OBSL1 functions as a substrate receptor for the CUL7-RING E3 ubiquitin ligase complex, where it acts as an adaptor bridging CUL7 to its substrate insulin receptor substrate 1 (IRS1). In concert with interacting proteins CCDC8 and TBC1D7, OBSL1 mediates the ubiquitination and subsequent proteasomal degradation of IRS1, thereby attenuating downstream phosphatidylinositol 3-kinase (PI3K)/AKT/mTOR signaling. Disruption of OBSL1 relieves IRS1 degradation, leading to enhanced AKT phosphorylation at Ser473, mTORC1 activation, and phosphorylation of ribosomal protein S6 kinase (S6K) at Ser235/236. Consequently, OBSL1 knockout amplifies proliferative and survival signals downstream of the insulin-like growth factor 1 (IGF-1) receptor, highlighting its role as a negative regulator of the IGF-1/PI3K/AKT axis.
In the context of Raji B lymphoma cells, OBSL1 knockout creates a model system for examining how deregulated IGF-1 signaling influences malignant B-cell growth. Since Raji cells harbor an EBV-driven proliferative program, the enhanced PI3K/AKT/mTOR output resulting from OBSL1 loss may synergize with viral oncogenic signals, offering insights into ubiquitin-dependent growth control and potential vulnerabilities in lymphoma. This model also serves as a platform for studying the molecular pathogenesis of 3-M syndrome, a primordial dwarfism associated with loss-of-function mutations in OBSL1, CUL7, or CCDC8, by allowing investigation of growth retardation mechanisms in a hematopoietic setting.
Researchers can employ OBSL1 Knockout Raji Polyclonal Cells to dissect IGF-1 signal transduction, ubiquitin-proteasome dynamics, and the 3-M complex. Assays include Western blotting for IRS1 and phospho-AKT (Ser473)/phospho-S6 (Ser235/236), co-immunoprecipitation with CUL7 or CCDC8, proliferation (MTS/MTT), cell cycle (propidium iodide), apoptosis (Annexin V), and RNA-seq. These enable therapeutic target screening in growth disorders or cancer. For further details, contact Ascent Research.
