Furin as proprotein convertase and its role in normal and pathological biological processes

Abstract

Furin belongs to serine intracellular Ca2+-dependent endopeptidases of the subtilisin family, also known as proprotein convertase (PC). Human furin is synthesized as zymogen with a molecular weight of 104 kDà, which is then activated by autocatalytic in two stages. This process can occur when zymogen migrates from the endoplasmic reticulum to the Golgi apparatus, where a large part of furin is accumulated. The molecular weigh t of the active furin is 98 kDà. Furin relates to enzymes with a narrow substrate specificity: it hydrolyzes peptide bonds at the site of paired basic amino acids and furin activity exhibits in a wide pH range 5-8. Its main biological function is activation of the functionally important protein precursors. It is accompanied by the launch of a cascade of reactions, which lead to appearance of biologically active molecules involved in realization of specific biological functions both in normal and in some patologicheskih processes. Furin substrates are biologically important proteins such as enzymes, hormones, growth factors and differentiation, receptors, adhesion proteins, proteins of blood plasma. Furin plays an important role in the development of processes such as proliferation, invasion, cell migration, survival, maintenance of homeostasis, embryogenesis, as well as the development of a number of pathologies, including cardiovascular, oncologic and neurodegenerative diseases. Furin and furin-like proprotein convertases participate as key factors in the realization of the regulatory functions of proteolytic enzymes, the value of which is currently being evaluated as most important in comparison with the degradative function of proteases.