Furin belongs to the family of subtilisin-like proprotein convertases. These convertases are in charge activating latent precursor proteins, which are processed into their biologically active fragments. Furin functions as a serin endoprotease.
Furin activates a variety of proteins
Furin cleaves and thus activates a number of proteins such as…
- Proparathyroid hormone
- Transforming Growth Factor beta 1 precursur (TGF-ß1 precursor)
- beta subunit of Pro-Nerve Growth Factor (NGF)
- Von Willebrand Factor
- Membranetype-1 Matrix Metalloprotease (MT1-MMP)
…. and a lot more.
All these factors in their activated forms are involved in several cellular mechanisms. As an example, I picked out the pathway which is triggered by Furin when activating MT1-MMP (see Figure 1). Activated MT1-MMP forms a complex with TIMP-2 on the cell surface and this complex on its part activates pro MMP-2. Active MMP-2 subsequently promotes cellular invasion. It’s obvious that Furin can play an important role in tumorigenesis by enhancing cell invasion. Naturally, Furin inhibitors have the potential to decrease proliferation and migration of cancer cells which has been most recently shown for lung adenocarcinoma cells (1).
Besides the activation of cellular precursor proteins, Furin is utilized by a number of pathogens. It has been shown that, e.g., the HIV envelope polyprotein precursor gp160 is proteolytically cleaved by Furin to gp120 and gp41 prior to viral assembly (2). Envelope proteins of viruses such as Influenza and Dengue Fever Virus have to be cleaved by Furin as well. Some bacterial toxins such as Anthrax toxin and Pseudomonas toxin, as well as Papillomaviruses have to be cleaved by Furin before entering host cells. Thus, Furin inhibitors are discussed as potential therapeutics for treating Anthrax infection (3).
Measuring Furin activity
Tools to measure Furin activity have been limited so far. The unique 3-step approach (Fig. 2) overcomes all limitations seen with FRET-based assays.
The assay is sensitive (as low as 0.5 pg/ul human or murine furin) and shows high linearity (0.5-16pg/ul; results with human and murine Furin shown in Fig 3).
If you are interested in measuring Furin activity or screening Furin inhibitors, don’t hesitate to get in touch by leaving your comments or questions below.
(1) Ma et al., Effect of Furin inhibitor on lung adenocarcinoma cell growth and metastasis, Cancer Cell International 14:43 (2014).
(2) Hallenberger et al., Inhibition of furin-mediated cleavage activation of HIV-1 glycoprotein gp160, Nature 360 (6402): 358–61 (1992).
(3) Shiryaev et al., Targeting host cell furin proprotein convertases as a therapeutic strategy against bacterial toxins and viral pathogens, J. Biol. Chem. 282 (29): 20847–53 (2007).