Chemically edited molecular glue in action: How 12-deoxyfusicoccin locks a repressor

A novel study uncovers how a subtle chemical tweak transforms the naturally occurring phytotoxin into a powerful molecular glue, 12-deoxyfusicoccin (12-dFC), that locks 14-3-3 proteins onto the intrinsically disordered translational repressor GIGYF2 in human cells. Through integrated proteomic, biochemical, and functional analyses, the work reveals an AMPK-driven stress pathway that 12-dFC exploits to shut down protein synthesis, rewire metabolism, and halt cell proliferation, pointing to an unexpected and promising strategy for targeting cancer cells.