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Typus
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Graf Isolan
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Untersuchte Arbeit:
Seite: 16, Zeilen: 17-29
Quelle: Feinstein-Rotkopf und Arama 2009
Seite(n): 980-981, Zeilen: 980:re.Sp. 16-21.27-31 - 981:li.Sp. 1-3.5-11
1.10.6. Caspase activity

Caspases, a unique family of cysteine-dependent aspartate specific proteases, play a pivotal role in cell death. The mammalian genome encodes fourteen distinct caspases, seven of which were shown to function in apoptosis (Chowdhury et al 2008).

Initiator caspases are activated through dimerization facilitated at multi-protein complexes. Activation of caspase-9, the initiator caspase of the intrinsic pathway, while the apical caspase of the extrinsic apoptotic pathway caspase-8 is activated within the death-inducing signaling complex (DISC) (Ashkenazi and Dixit 1998; Boatright and Salvesen 2003b). On the other hand, activation of effector caspases, such as caspase-3 and -7 occurs upon their cleavage at specific internal aspartic acid residues by initiator caspases (Boatright and Salvesen 2003a). Downstream of this activational cascade, caspases cleave a variety of regulatory and structural proteins and important enzymes, ultimately leading to cell death (Gradzka 2006; Pop and Salvesen 2009).


Ashkenazi,A., Dixit,V.M., 1998. Death receptors: signaling and modulation. Science 281, 1305-1308.

Boatright,K.M., Salvesen,G.S., 2003a. Mechanisms of caspase activation. Curr. Opin. Cell Biol. 15, 725-731.

Chowdhury,I., Tharakan,B., Bhat,G.K., 2008. Caspases - an update. Comp Biochem. Physiol Biochem. Mol. Biol. 151, 10-27.

Gradzka,I., 2006. [Mechanisms and regulation of the programmed cell death]. Postepy Biochem. 52, 157-165.

Pop,C., Salvesen,G.S., 2009. Human caspases: Activation, specificity and regulation. J. Biol. Chem.

[Seite 980]

Introduction

[...] A key feature of apoptosis is the activation of a unique family of cysteine-dependent aspartate specific proteases called caspases. The mammalian genome encodes fourteen distinct caspases, seven of which were shown to function in apoptosis and will henceforth be termed apoptotic caspases or simply caspases [16, 17].

[...] Initiator caspases are activated through dimerization facilitated at multi-protein complexes. Activation of caspase-9, the initiator caspase of the intrinsic pathway, involves its recruitment to the apoptosome by Apaf-1-Cyt c complex,

[Seite 981]

while the apical caspase of the extrinsic apoptotic pathway caspase-8 is activated within the death-inducing signaling complex (DISC) [25–29]. [...] On the other hand, activation of effector caspases, such as caspase-3 and -7 occurs upon their cleavage at specific internal aspartic acid residues by initiator caspases [28, 29]. Downstream of this activational cascade, caspases cleave a variety of regulatory and structural proteins and important enzymes, ultimately leading to cell death.


16. Petrilli V, Dostert C, Muruve DA, Tschopp J (2007) The inflammasome: a danger sensing complex triggering innate immunity. Curr Opin Immunol 19:615–622. doi:10.1016/j.coi.2007.09.002

17. Chowdhury I, Tharakan B, Bhat GK (2008) Caspases — an update. Comp Biochem Physiol B Biochem Mol Biol 151:10–27. doi:10.1016/j.cbpb.2008.05.010

25. Zou H, Henzel WJ, Liu X, Lutschg A, Wang X (1997) Apaf-1, a human protein homologous to C elegans CED-4, participates in cytochrome c-dependent activation of caspase-3. Cell 90:405–413. doi:10.1016/S0092-8674(00)80501-2

26. Ashkenazi A, Dixit VM (1998) Death receptors: signaling and modulation. Science 281:1305–1308. doi:10.1126/science.281.5381.1305

27. Rodriguez J, Lazebnik Y (1999) Caspase-9 and APAF-1 form an active holoenzyme. Genes Dev 13:3179–3184. doi:10.1101/gad.13.24.3179

28. Boatright KM, Salvesen GS (2003) Mechanisms of caspase activation. Curr Opin Cell Biol 15:725–731. doi:10.1016/j.ceb.2003.10.009

29. Riedl SJ, Shi Y (2004) Molecular mechanisms of caspase regulation during apoptosis. Nat Rev Mol Cell Biol 5:897–907. doi:10.1038/nrm1496

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