BACKGROUND Cardiac fibrosis after primary infarction is a type of pathological phenomena as shown by increased collagen in myocardial cells. Transforming growth factor (TGF)-β1 is a critical factor participating in myocardial fibrosis. A previous study has shown the inhibitory role on TGF-β1 by microRNA-24 (miR-24) via targeting Furin. This study thus investigated the role of miR-24 and Furin/T...

Furin, a potent proprotein convertase involved in activation of several cancer-related substrates, is synthesized as an inactive zymogen, thus minimizing the occurrence of premature enzymatic activity that would lead to inappropriate protein activation or degradation. This natural inhibitory mechanism is based on the presence of an inactivating prosegment at the NH2 terminal of the zymogen. Aft...

Current antiviral strategies target viral gene products. Although initially successful, their severe toxicity and susceptibility to circumvention by the generation of drug-resistant variants limit their usefulness. By contrast, the central role of the host cell serine endoprotease furin in the proteolytic activation of numerous pathogens points to the endoprotease as a strategic target for ther...

Furin is a membrane-associated endopeptidase located in the trans-Golgi network that has the enzymatic capabilities to process a large number of precursors (6,11). Furin catalyzes the cleavage of a specific sequence (R-6X-5-R-4-X-3-R/Lys-2-R-1) with the added condition that there is no hydrophobic aliphatic amino acid at position +1 (12). Furin substrate sequence occurs in many proteins, includ...

Improperly folded membrane proteins are retained in the endoplasmic reticulum and then diverted to a degradative pathway by a network of molecular chaperones and intracellular proteases. Here we report that mutant insulin proreceptors (Pro(62)) retained in the early secretory pathway undergo proteolytic cleavage at a tetrabasic concensus site for the subtilisin-like protease furin (SPC 1), gene...

Real-time imaging of cell-surface-associated proteolytic enzymes is critical to better understand their performances in both physiological and pathological processes. However, most current approaches are limited by their complexity and poor membrane-anchoring properties. Herein, we have designed and synthesized a unique small-molecule fluorescent probe, which combines the principles of passive ...

Furin inhibitors are promising therapeutics for the treatment of cancer and numerous infections caused by bacteria and viruses, including the highly lethal Bacillus anthracis or the pandemic influenza virus. Development and improvement of inhibitors for pharmacological use require a detailed knowledge of the protease's substrate and inhibitor binding properties. Here we present a novel preparat...

Open reading frame IV (ORF-IV) of Borna disease virus (BDV) encodes a protein with a calculated molecular mass of ca. 57 kDa (p57), which increases after N glycosylation to 94 kDa (gp94). The unglycosylated and glycosylated proteins are proteolytically cleaved by the subtilisin-like protease furin. Furin most likely recognizes one of three potential cleavage sites, namely, an arginine at positi...

The alphavirus Semliki Forest virus (SFV) infects cells via a low-pH-dependent membrane fusion reaction mediated by the E1 envelope protein. Fusion is regulated by the interaction of E1 with the receptor-binding protein E2. E2 is synthesized as a precursor termed "p62," which forms a stable heterodimer with E1 and is processed late in the secretory pathway by a cellular furin-like protease. Onc...

The proteolytic activity of Furin responsible for processing full length Notch-1 (p300) plays a critical role in Notch signaling. The amplitude and duration of Notch activity can be regulated at various points in the pathway, but there has been no report regarding regulation of the Notch-1-Furin interaction, despite its importance. In the present study, we found that the Notch-1-Furin interacti...