Department of Pathology, University Medical Center Utrecht, Utrecht, Netherlands.
Cardiovascular Epidemiology Unit, Department of Public Health & Primary Care, University of Cambridge, Cambridge, United Kingdom.
Front Immunol. 2021 May 4;12:677707. doi: 10.3389/fimmu.2021.677707. eCollection 2021.
Granzymes are a family of serine proteases stored in granules inside cytotoxic cells of the immune system. Granzyme K (GrK) has been only limitedly characterized and knowledge on its molecular functions is emerging. Traditionally GrK is described as a granule-secreted, pro-apoptotic serine protease. However, accumulating evidence is redefining the functions of GrK by the discovery of novel intracellular (e.g. cytotoxicity, inhibition of viral replication) and extracellular roles (e.g. endothelial activation and modulation of a pro-inflammatory immune cytokine response). Moreover, elevated GrK levels are associated with disease, including viral and bacterial infections, airway inflammation and thermal injury. This review aims to summarize and discuss the current knowledge of i) intracellular and extracellular GrK activity, ii) cytotoxic and non-cytotoxic GrK functioning, iii) the role of GrK in disease, and iv) GrK as a potential therapeutic target.
颗粒酶是储存在免疫系统细胞毒性细胞颗粒内的丝氨酸蛋白酶家族。颗粒酶 K（GrK）的特性仅有限地描述，其分子功能的知识正在出现。传统上，GrK 被描述为颗粒分泌的促凋亡丝氨酸蛋白酶。然而，新的发现正在重新定义 GrK 的功能，包括新型的细胞内（例如细胞毒性、抑制病毒复制）和细胞外作用（例如内皮激活和促炎免疫细胞因子反应的调节）。此外，GrK 水平升高与疾病有关，包括病毒和细菌感染、气道炎症和热损伤。这篇综述旨在总结和讨论目前关于 i）细胞内和细胞外 GrK 活性、ii）细胞毒性和非细胞毒性 GrK 功能、iii）GrK 在疾病中的作用以及 iv）GrK 作为潜在治疗靶点的知识。
