The ERLIN1 Knockout Raji Polyclonal Cells represent a CRISPR/Cas9-edited polyclonal knockout cell population generated from the Raji human B lymphocyte cell line, featuring disruption of the ERLIN1 gene. This heterogeneous pool of cells with ERLIN1 loss-of-function enables robust functional studies while minimizing clonal artifacts, providing a physiologically relevant model for investigating gene function in a population context. The polyclonal format preserves natural allelic variation, ensuring that downstream phenotypes reflect the collective impact of ERLIN1 disruption across a broad cellular background.
Raji is a suspension-adapted, Epstein-Barr virus (EBV)-positive lymphoblastoid cell line derived from a Burkitt lymphoma patient. These B lymphocytes retain key characteristics of antigen-presenting cells and actively engage in B cell receptor signaling, making them an extensively used model for studying B cell malignancies, immune responses, and lymphomagenesis. The transformed nature of Raji cells, combined with their EBV-driven proliferation, provides a unique platform to explore the interplay between ER homeostasis, cholesterol metabolism, and oncogenic signaling in B cell-derived cancers.
ERLIN1 encodes an endoplasmic reticulum (ER) lipid raft-associated protein that functions as a critical facilitator of ER-associated protein degradation (ERAD) and a regulator of cholesterol homeostasis. At the molecular level, ERLIN1 forms functional complexes with its homolog ERLIN2, the ubiquitin ligase AMFR/gp78, RNF170, and INSIG1, and physically interacts with the retrotranslocation machinery components Derlin-1 and VCP/p97. Upstream, ERLIN1 expression and activity are modulated by the ER stress transducers ATF6, IRE1??, and PERK, as well as by the sterol regulatory element-binding protein SREBP-2, a master transcriptional regulator of cholesterol biosynthesis. Downstream, ERLIN1 impacts the stability and function of inositol 1,4,5-trisphosphate receptors (IP3Rs) and substrates of the ERAD pathway, and influences the expression of cholesterol synthesis enzymes such as HMG-CoA reductase (HMGCR). Disruption of ERLIN1 cripples the ERAD machinery, leading to reduced degradation of misfolded glycoproteins and altered lipid raft composition, which collectively trigger proteotoxic stress and dysregulated cholesterol metabolism.
In the Raji B lymphocyte context, ERLIN1 knockout profoundly disrupts ERAD-mediated protein quality control, a process essential for proper folding and degradation of immunoglobulins and key signaling molecules. The accumulation of misfolded proteins and aberrant cholesterol trafficking can impair lipid raft integrity, which is critical for B cell receptor clustering and downstream signal transduction. This model thus recapitulates molecular features relevant to B cell malignancies, hereditary spastic paraplegia, and other ER stress-related disorders, offering a valuable platform to dissect how ERAD dysfunction contributes to lymphomagenesis and neurodegeneration.
Typical research applications include mechanistic studies of the unfolded protein response (UPR) and ER stress pathways in B cell lymphomas, functional analyses of cholesterol metabolism in cancer, drug target validation for ERAD inhibitors, and investigation of hereditary spastic paraplegia-associated genes. This polyclonal knockout pool is compatible with a variety of robust assays: Western blotting for ERAD substrates and UPR markers (e.g., BiP/GRP78), RT-qPCR for cholesterol synthesis genes (such as HMGCR), flow cytometry for apoptosis (Annexin V), cholesterol efflux assays, and immunofluorescence for ER stress markers. Researchers can employ these cells to assess the impact of ERAD inhibition on B cell survival and to screen for modulators of lipid raft-dependent signaling. For further technical inquiries or ordering information, please contact Ascent Research.
