Granzyme B: pro-apoptotic, antiviral and antitumor functions

Curr Opin Immunol. 2003 Oct;15(5):533-43. doi: 10.1016/s0952-7915(03)00107-9.

Abstract

Granzyme B is a caspase-like serine protease that is released by cytotoxic lymphocytes to kill virus-infected and tumor cells. Major recent advances in our understanding of granzyme B biochemistry, biology and function include an appreciation of its uptake into and trafficking within target cells, a thorough dissection of how cell death is triggered, and the identification of the serpin protease inhibitor PI-9, which regulates its function in lymphocytes and in other cells. The roles that granzyme B plays in human pathologies, such as transplant rejection, viral immunity and particularly tumor immune surveillance, remain a topic for vigorous debate and conjecture. The recent discovery of a triply mutated human granzyme B allele, whose product is predicted to possess a reduced capacity to induce cell death, opens the way for major progress in these areas in coming years.

Publication types

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

MeSH terms

  • Apoptosis / immunology*
  • Apoptosis / physiology
  • BH3 Interacting Domain Death Agonist Protein
  • Carrier Proteins / physiology
  • Graft Rejection / enzymology
  • Granzymes
  • Humans
  • Membrane Glycoproteins / metabolism
  • Mitochondria / metabolism
  • Neoplasms / enzymology
  • Neoplasms / immunology*
  • Perforin
  • Pore Forming Cytotoxic Proteins
  • Receptor, IGF Type 2 / metabolism
  • Serine Endopeptidases / physiology*
  • Serpins / metabolism
  • Serpins / physiology
  • Signal Transduction
  • Substrate Specificity
  • T-Lymphocytes, Cytotoxic / enzymology
  • Virus Diseases / enzymology
  • Virus Diseases / immunology*

Substances

  • BH3 Interacting Domain Death Agonist Protein
  • BID protein, human
  • Carrier Proteins
  • Membrane Glycoproteins
  • Pore Forming Cytotoxic Proteins
  • Receptor, IGF Type 2
  • SERPINB9 protein, human
  • Serpins
  • Perforin
  • GZMB protein, human
  • Granzymes
  • Serine Endopeptidases