Biology of granzyme M: a serine protease with unique features

Crit Rev Immunol. 2009;29(4):307-15. doi: 10.1615/critrevimmunol.v29.i4.20.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cell Death
  • Gene Expression
  • Granzymes / antagonists & inhibitors
  • Granzymes / chemistry
  • Granzymes / genetics
  • Granzymes / metabolism*
  • Humans
  • Protease Inhibitors / pharmacology
  • Substrate Specificity

Substances

  • Protease Inhibitors
  • Granzymes