Review article

Background, biology and significance of human granzymes

Marijana Ručević ; Faculty of Food Technology and Biotechnology, University of Zagreb, Zagreb, Croatia
Loren D. Fast ; Rhode Island Hospital/Brown University, Providence, Rhode Island, USA

Abstract

The human granzymes (Grz) are a highly conserved group of potent peptidases that are found, together with a pore forming protein-perforin in specialized granules of cytotoxic cells such as cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells. Granule exocytosis (perforin/Grz) pathway is used by these cells to defend organism against virus-infected and tumor cells by inducing them to undergo apoptosis. While the pro-apoptotic functions of Grz have been well established, it has recently become apparent that Grz also possess important extracelular activities which are now being extensively investigated. Soluble Grz are found extracellularly in normal plasma suggesting their constitutive secretion in healthy individuals via a
granule independent biosynthetic pathway. The potent activities of extracellular Grz appear to be controlled by highly abundant plasma derived serine peptidase inhibitors. However, unregulated activities of proteolytic Grz have been shown to result in disease pathology especially, in the absence of their corresponding inhibitors. To date, most of the studies have concentrated on the structure and function of granzyme A (GrA) and GrB while very little work has been done on the remaining Grz which include GrM, GrH and GrK in humans. In this report, we discuss the current knowledge of Grz biochemistry, biology, functions, activity regulation and their role in human pathology with special emphasis on the significance of human GrK
in this field.

Keywords

Cytotoxic T lymphocytes; Natural killer cells; Granzymes; Granzyme K; Apoptosis; Extacellular activities; Human pathology

Hrčak ID:

29051

URI

https://hrcak.srce.hr/29051

Publication date:

29.2.2008.

Visits: 1.584 *