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

Abstract

Furin belongs to intracellular serine Ca²⁺-dependent endopeptidases of the subtilisin family, also known as proprotein convertases (PC). Human furin is synthesized as a zymogen with a molecular weight of 104 kDа, which is then autocatalytically activated in two stages. This process occurs during zymogen migration from the endoplasmic reticulum to the Golgi apparatus, where a large part of furin is accumulated. The molecular weight of the active furin is 98 kDа. Furin is the enzyme with narrow substrate specificity: it hydrolyzes peptide bonds at the site of paired basic amino acids and is active in a wide range of pH (5.0–8.0). The main biological function of furin as PC consists in activation of functionally important protein precursors. This is accompanied by initiation of cascades of reactions, which lead to appearance of biologically active molecules involved in realization of specific biological functions both in normal and in some pathological processes. The list of furin substrates includes biologically important proteins such as enzymes, hormones, growth/differentiation, receptors, adhesion proteins, plasma proteins. Furin plays an important role in the development of such processes as proliferation, invasion, cell migration, survival, maintenance of homeostasis, embryogenesis, as well as the development of a number of pathologies, including cardiovascular, cancer, and neurodegenerative diseases. Furin and furin-like proprotein convertases are key factors in the realization of the regulatory functions of proteolytic enzymes; the latter is currently considered as the most important function (compared with well recognized protease function in degradation of proteins).