Target identification for small-molecule discovery in the FOXO3a tumor-suppressor pathway using a biodiverse peptide library

Genetic screening technologies to identify and validate macromolecular interactions (MMIs) essential for complex pathways remain an important unmet need for systems biology and therapeutics development. Here, we use a library of peptides from diverse prokaryal genomes to screen MMIs promoting the nuclear relocalization of Forkhead Box O3 (FOXO3a), a tumor suppressor more frequently inactivated by post-translational modification than mutation.

Citation:
Emery A, Hardwick BS, Crooks AT, Milech N, Watt PM, Mithra C, et al. Target identification for small-molecule discovery in the FOXO3a tumor-suppressor pathway using a biodiverse peptide library. Cell Chem Biol. 2021;28(11):1602-15.e9.

Keywords:
14-3-3; bioactive peptide; FOXO3a; lead discovery; phenotypic screening; prokaryal genomes; protein interference; protein-protein interaction; target identification; target validation

Abstract:
Genetic screening technologies to identify and validate macromolecular interactions (MMIs) essential for complex pathways remain an important unmet need for systems biology and therapeutics development. Here, we use a library of peptides from diverse prokaryal genomes to screen MMIs promoting the nuclear relocalization of Forkhead Box O3 (FOXO3a), a tumor suppressor more frequently inactivated by post-translational modification than mutation.