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Critical Reviews™ in Immunology

Impact factor: 3.698

ISSN Print: 1040-8401
ISSN Online: 2162-6472

Critical Reviews™ in Immunology

DOI: 10.1615/CritRevImmunol.v29.i4.20
pages 307-315

Biology of Granzyme M: A Serine Protease with Unique Features

Pieter J. A. de Koning
Department of Pathology, University Medical Centre Utrecht, Utrecht, The Netherlands
J. Alain Kummer
Department of Pathology, University Medical Centre Utrecht, Utrecht, The Netherlands
Niels Bovenschen
Department of Pathology, University Medical Centre Utrecht, Utrecht, The Netherlands

ABSTRACT

The granule-exocytosis pathway is the major mechanism for cytotoxic lymphocytes to kill tumor cells and virus-infected cells. Cytotoxic granules contain the pore-forming protein perforin and a set of structurally homologues serine proteases called granzymes. Perforin facilitates the entry of granzymes into a target cell, allowing these proteases to initiate distinct cell death routes by cleaving specific intracellular substrates. The family of granzymes consists of multiple members, of which granzyme A and granzyme B have been studied most extensively. Since the cloning of the granzyme M cDNA in the early 1990s, it has remained an "orphan" granzyme for many years and only during the past few years the interest in this protease has increased. Granzyme M appears to be a potent inducer of tumor cell death with morphological hallmarks that are unique among all granzymes. In this review, we summarize the characteristics of granzyme M that are currently known, including its cellular expression, substrate specificity, physiological functions, and inhibitors.