Discovery of the Proprotein Convertases and their Inhibitors

The members of the convertase family play a central role in the processing of various protein precursors ranging from hormones and growth factors to viral envelope proteins and bacterial toxins. The proteolysis of these precursors that occurs at basic residues is mediated by the proprotein convertases (PCs), namely: PC1, PC2, Furin, PACE4, PC4, PC5 and PC7. The proteolysis at non-basic residues is performed by subtilisin/kexin-like isozyme-1 (S1P/SKI-1) and the newly identified neural apoptosis-regulated convertase-1 (NARC-1/PCSK9). These proteases have key roles in many physiological processes and various pathologies including cancer, obesity, diabetes, neurodegenerative diseases and autosomal dominant hypercholesterolermia. Here we summarize the discovery of the proprotein convertases and their inhibitors, discuss their properties, roles, resemblance and differences