Many proprotein convertases, especially furin and PACE4, are involved in pathological processes such as viral infection, inflammation, hypercholesterolemia, and cancer, and have been postulated as therapeutic targets for some of these diseases.
In 1984, David Julius, working in the laboratory of Jeremy Thorner, identified the product of the Kex2 gene as responsible for processing of the alpha factor mating pheromone.
This suggests a potential mechanism to generate the soluble forms of HJV/hemojuvelin (s-hemojuvelin) found in the blood of rodents and humans.
PC1 (also known as PC3 and commonly referred to as PC1/3) and PC2 are the primary enzymes involved in the processing of the bioactive peptides precursors at paired basic residues.
[9] PC1/3 and PC2 do not directly produce most neuropeptides and peptide hormones, but instead generate intermediates that contain C-terminal extensions of lysine and/or arginine residues; these are subsequently removed by carboxypeptidase E. Current scientific evidence indicates that both up- and down-regulation of the expression of proprotein convertases are part of the multiple changes occurring in gynecological tumors.
PCs activate crucial substrates implicated in the progression of gynecological cancers, including adhesion molecules, metalloproteinases, and viral proteins.
Experimental evidences suggest that careful targeting of PCs in gynecological cancer may represent a feasible strategy to deter tumor progression.