Fusicoccin: A chemical modulator for 14-3-3 proteins

Abstract

Diterpene glucoside fusicoccin A (FC-A) is a phytotoxic fungal metabolite that stabilizes the interactions between 14-3-3 protein and phosphorylated ligand protein. 14-3-3-mediated protein binding is central to the regulation of the serine/threonine kinase signaling pathway in all eukaryotic cells and is essential for controlling numerous biological processes. Thus, fusicoccins could serve as a robust platform for developing new chemical probes and pharmaceuticals. This review describes recent progress toward understanding the biosynthetic pathways of fusicoccins and the rational design of 14-3-3 inhibitors and stabilizers, as well as their antitumor activities.