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Pathways for Cytolysis pp 95–119Cite as

Granzymes and Apoptosis: Targeting the Cell Cycle

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Part of the book series: Current Topics in Microbiology and Immunology ((CT MICROBIOLOGY,volume 198))

Abstract

The ability of cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells to kill susceptible targets has been known for over 20 years. This observation led to an intensive if not somewhat prolonged search for the molecular mediators of cell death. With the knowledge that is now available to us, and which will be discussed here and in the various chapters of this volume, it is clear that killing involves at least two different pathways. The first is initiated by the content of the cytoplasmic granules which are exocytosed towards the target cell (Henkart 1985; Golstein et al. 1991). The second results from activation of the Fas receptor on the target by its ligand on the effector cell (Rouvier et al. 1993; Itoh et al. 1991; Suda et al. 1993; Vignaux and Golstein 1994). If it were not sufficiently complex that a cell uses two killing pathways, it also appears that cell death induced by granule exocytosis may utilize several molecular mediators: the pore forming protein perforin (Henkart et al. 1984; Podack et al. 1985, 1991), a group of CTL/NK-specific granule serine proteases known as granzymes (Hayes et al. 1989; Shiet al. 1992 a, b, 1994; Shiver et al. 1992) and perhaps a poly(A)-binding protein TIA-1 (Tian et al. 1991; Kawakami et al. 1992). Thus, it is not surprising that the mechanisms of CTL killing have revealed themselves only slowly.

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  1. Manitoba Institute of Cell Biology, University of Manitoba, 100 Olivia Street, Winnipeg, Manitoba, R3E OV9, Canada

    A. H. Greenberg & D. W. Litchfield

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  1. Basel Institute of Immunology, Grenzacherstr. 487, 4005, Basel, Switzerland

    Gillian M. Griffiths

  2. Department of Biochemistry, University of Lausanne, Ch. Boveresses 155, 1066, Epalinges/Lausanne, Switzerland

    Jürg Tschopp

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Greenberg, A.H., Litchfield, D.W. (1995). Granzymes and Apoptosis: Targeting the Cell Cycle. In: Griffiths, G.M., Tschopp, J. (eds) Pathways for Cytolysis. Current Topics in Microbiology and Immunology, vol 198. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-79414-8_6

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