Furin-mediated protein processing in infectious diseases and cancer

Braun, Elisabeth; Sauter, Daniel

Since many viral pathogens rely on furin or related PCSKs for the maturation of their own (glyco)proteins, GBP2 and GBP5 exert broad antiviral activity, inhibiting replication of highly pathogenic avian influenza A, measles and Zika viruses. In contrast, GBP2 and GBP5 do not decrease infectivity of virions carrying the glycoprotein of vesicular stomatitis virus, which does not require a proteolytic activation step. Notably, inhibition of furin in infected cells comes at a cost, since furin-mediated processing of matrix metalloproteinases and other cellular substrates is also reduced in the presence of increased GBP2 or GBP5 levels. 96 Future experiments will reveal whether PAR-1-or GBPmediated inhibition of furin activity may also prevent the development or proliferation of certain cancers. Remarkably, increased GBP2/5 expression is associated with favorable outcome in patients suffering from melanoma or breast cancer. 97, 98 Thus, a better understanding of cellular mechanisms regulating furin activity will help to understand the pathogenesis of infectious diseases and cancer and may uncover novel targets for therapeutic intervention.