Nabil G. Seidah

Accredited  Professor

Contact Information

Institut de recherches cliniques de Montréal
110, avenue des Pins ouest
Montréal (Québec)
H2W 1R7


T 514 987-5609
F 514 979-5542
Site web


Secretory proprotein convertases

We are interested in the elucidation at the molecular, cellular and in vivo levels of the mechanisms of the biosynthetic machinery and its components that are critical for the intracellular and extracellular processing and maturation of secretory proteins, prohormones and zymogens in general. Such proteolytic processing resulting in activation or inactivation of proteins, mostly occurs at the C-terminus of either single or paired basic amino acids but also at non basic residues. The 9 proprotein convertases known that we recently cloned and/or extensively characterized are: PC1, PC2, Furin, PC4, PACE4, PC5, PC7 as well as SKI-1 and PCSK9. We are elucidating the implication of these convertases in disease states and pathologies such as cancer, neurodegenerative diseases, viral infections, and dyslipidemia such as atherosclerosis and hyperholesterolemia both in human and in animal models. Thus, we have shown that the convertases SKI-1 and PCSK9 play major roles in the metabolism and/or synthesis of cholesterol and fatty acids. The development of knockout and transgenic mice with loss or gain of function of some convertases allowed us to better define their in vivo functions in normal and disease states. We have recently identified specific ways to inhibit these enzymes leading the way to clinical applications in pathologies, especially for PCSK9 in the treatment of hypercholesterolemia.


  • Seidah N.G., Benjannet S, Wickham L, Marcinkiewicz J, Bélanger-Jasmin S, Stifani S, Basak A, Prat A, and Chrétien M: The secretory proprotein convertase neural apoptosis-regulated convertase 1 (NARC-1): Liver regeneration and neuronal differentiation. Proc Natl Acad Sci U S A., 100: 928-933, 2003
  • Benjannet S., Rhainds D., Essalmani R., Mayne J., Wickham L., Jin W., Asselin M.-C., Hamelin J., Varret M., Allard D., Trillard M., Abifadel M., Tebon A., Attie A.D., Rader D.J., Boileau C., Brissette L, Chrétien M., Prat A. and Seidah N.G.: NARC-1/PCSK9 and its natural mutants: zymogen cleavage and effects on the LDLR and LDL-cholesterol. J Biol Chem., 279: 48865-48875, 2004
  • Pasquato A., Pullikotil P., Asselin M-C., Vacatello M., Paolillo L., Ghezzo , Basso F.,Bello C., Dettin M., Seidah N.G. The Proprotein convertase SKI-1/S1P: in vitro analysis of lassa virus glycoprotein-derived substrates and ex vivo validation of irreversible peptide inhibitors J Biol Chem, 281: 23471-23481, 2006
  • Pullikotil P, Benjannet S, Mayne J, Seidah N.G. The proprotein convertase SKI-1/S1P: Alternate translation and subcellular localization. J Biol Chem., 282: 27402-27413, 2007
  • Seidah N.G. and Prat A. The proprotein convertases are potential targets in the treatment of dyslipidemia. J Mol Med., 85: 685-696, 2007
  • Nassoury N., Blasiole D., Oler T. A., Benjannet S., Hamelin J., Attie A.D., Prat A., and Seidah N.G. The cellular trafficking of the secretory proprotein convertase PCSK9 and its dependence on the LDLR. Traffic, 6: 718-732, 2007
  • Essalmani R., Zaid A., Marcinkiewicz J., Chamberland A., Pasquato A., Seidah N. G. and Prat A..In vivo functions of the proprotein convertase PC5/6 during mouse development: Gdf11 is a major substrate. Proc Natl Acad Sci U S A. 105:5750-5755, 2008
  • Zaid A., Roubtsova A., Essalmani R., Marcinkiewicz E., Chamberland A., Hamelin J., Tremblay M., Jacques H., Jin W., Davignon J., Seidah N.G. and Prat A.: PCSK9: hepatocyte-specific LDL receptor degradation and critical role in liver regeneration. Hepatology, 48: 646-54, 2008
  • Mayer G., Hamelin J., Asselin M.-C., Pasquato A., Marcinkiewicz E., Tang M., Tabibzadeh S. and Seidah N.G. The regulated cell-surface zymogen activation of the proprotein convertase PC5A directs the processing of its secretory substrates, J. Biol Chem. 283:2373-84, 2008
  • Poirier S., Mayer G, Benjannet S., Bergeron E., Marcinkiewicz J., Nassoury N., Mayer H., Nimpf J., Prat A. and Seidah N.G. The Proprotein Convertase PCSK9 Induces the degradation of LDLR and its closest family members VLDLR and apoER2. J Biol Chem. 283:2363-72, 2008