Mouse Mammary Gland Morphogenic Differences with BAD 3SA Mutant

The identification of genes driving organ development is central to understanding which signaling pathways drive the pathogenesis of various diseases including cancer. This dataset depicts the proteomic changes observed in C57BL/6J mice expressing wild-type or 3SA-phospho mutant versions of the Bcl-2-associated death promoter, BAD. This data shows that BAD regulates postnatal mammary gland morphogenesis in puberty. Three conserved serine residues on BAD are co-ordinately phosphorylated to regulate its activity. Non-phosphorylated BAD mutant delayed pubertal ductal elongation. This defect was specific to the epithelial compartment as transplant and ex vivo organoid assays of mutant epithelium recapitulated decreased tubule migration. Proteomic signature between BAD+/+ and phosphomutant BAD-3SA mammary glands identified differences in actin-binding and focal adhesion components. Mechanistically, non-phosphorylated BAD impedes protein translation, specifically in protrusions, through aberrant hypophosphorylated 4E-BP1. These findings reveal a critical enhancement of localized translation for efficient pubertal-mammary-gland morphogenesis and identifies BAD as a novel regulator of this process.