The EIF4EBP1 Knockout 769-P Polyclonal Cells are a CRISPR/Cas9-edited polyclonal population with targeted disruption of the EIF4EBP1 gene in the human 769-P renal cell carcinoma line. This loss-of-function model enables investigation of cap-dependent translation regulation in a ccRCC context. The polyclonal format preserves genetic heterogeneity, suitable for population-level studies.
The 769-P cell line is derived from a human, male clear cell renal cell carcinoma, an aggressive kidney cancer subtype characterized by frequent mTOR pathway activation. These epithelial cells retain key oncogenic features and are widely used to study ccRCC biology. Their reliance on mTOR signaling for proliferation and survival makes them an ideal host for investigating EIF4EBP1’s role in translation repression.
EIF4EBP1 (4E-BP1) functions as a translation repressor by binding eIF4E to inhibit eIF4F complex formation, thereby blocking cap-dependent translation. This repression is alleviated by mTORC1-mediated phosphorylation in response to upstream PI3K/AKT, insulin/IGF-1, and amino acid sufficiency. Phosphorylated EIF4EBP1 releases eIF4E, enabling translation initiation of growth-promoting mRNAs, including 5’TOP mRNAs. Key interacting partners include eIF4E, mTORC1, and Raptor, with pathway components such as mTOR, S6K1, AKT, and PI3K. Thus, EIF4EBP1 acts downstream of mTORC1 and interacts directly with eIF4E to orchestrate translational control.
In ccRCC, mTOR pathway aberrations drive constitutive EIF4EBP1 phosphorylation, promoting oncogenic translation. The knockout in 769-P cells allows dissection of EIF4EBP1’s role as a tumor suppressor and translational brake. This model facilitates examination of how loss of EIF4EBP1 impacts cell growth, global protein synthesis, and sensitivity to mTOR inhibitors like rapamycin, reflecting the heterogeneous ccRCC scenario.
This product supports a variety of experimental approaches: western blotting with phospho-4E-BP1 antibodies to assess mTOR activity, cap-binding assays to measure eIF4E availability, polysome profiling for translation efficiency, cell proliferation assays, and drug sensitivity testing using rapamycin or other mTOR inhibitors. RT-qPCR targeting 5’TOP mRNAs provides a readout of translational output. These applications span mTOR signaling studies, translation regulation, renal cell carcinoma research, and metabolic disorder investigations. For technical assistance or more details, please contact Ascent Research.
