Computational inference of eIF4F complex function and structure in human cancers.

amplification or duplication may be positively selected for its beneficial impact on the overexpression of cancer survival genes. The co-regulation of eIF4G1 and eIF4A1, distinctly from eIF4E, reveals eIF4F dysregulation favoring cap-independent initiation. Alphafold predicts changes in the eIF4F complex assembly to accommodate both initiation mechanisms. These findings have significant implications for evaluating cancer cell vulnerability to eIF4F inhibition and developing treatments that target cancer cells with dependency on the translation initiation mechanism.