Biology of granzyme M: a serine protease with unique features.
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.
de Koning
Pieter J A
PJ
Department of Pathology, University Medical Centre Utrecht, The Netherlands.
Kummer
J Alain
JA
Bovenschen
Niels
N
D000818:Animals; D016923:Cell Death; D015870:Gene Expression; D053804:Granzymes / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D011480:Protease Inhibitors / Q000494:pharmacology; D013379:Substrate Specificity
D011480:Protease Inhibitors; D053804:Granzymes