Braun Elisabeth, Sauter Daniel
Institute of Molecular Virology Ulm University Medical Center Ulm Germany.
Clin Transl Immunology. 2019 Aug 5;8(8):e1073. doi: 10.1002/cti2.1073. eCollection 2019.
Proteolytic cleavage regulates numerous processes in health and disease. One key player is the ubiquitously expressed serine protease furin, which cleaves a plethora of proteins at polybasic recognition motifs. Mammalian substrates of furin include cytokines, hormones, growth factors and receptors. Thus, it is not surprising that aberrant furin activity is associated with a variety of disorders including cancer. Furthermore, the enzymatic activity of furin is exploited by numerous viral and bacterial pathogens, thereby enhancing their virulence and spread. In this review, we describe the physiological and pathophysiological substrates of furin and discuss how dysregulation of a simple proteolytic cleavage event may promote infectious diseases and cancer. One major focus is the role of furin in viral glycoprotein maturation and pathogenicity. We also outline cellular mechanisms regulating the expression and activation of furin and summarise current approaches that target this protease for therapeutic intervention.
蛋白水解切割调节着健康和疾病中的众多过程。一个关键因素是广泛表达的丝氨酸蛋白酶弗林蛋白酶，它在多碱性识别基序处切割大量蛋白质。弗林蛋白酶的哺乳动物底物包括细胞因子、激素、生长因子和受体。因此，弗林蛋白酶活性异常与包括癌症在内的多种疾病相关也就不足为奇了。此外，许多病毒和细菌病原体利用弗林蛋白酶的酶活性，从而增强它们的毒力和传播。在本综述中，我们描述了弗林蛋白酶的生理和病理生理底物，并讨论了一个简单的蛋白水解切割事件的失调如何促进传染病和癌症。一个主要重点是弗林蛋白酶在病毒糖蛋白成熟和致病性中的作用。我们还概述了调节弗林蛋白酶表达和激活的细胞机制，并总结了目前针对这种蛋白酶进行治疗干预的方法。
