The central role of initiator caspase-9 in apoptosis signal transduction and the regulation of its activation and activity on the apoptosome
| Autor: | Maximilian L. Würstle, Maike A. Laussmann, Markus Rehm |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
Caspase-9
0303 health sciences Proteases biology Intrinsic apoptosis Caspase 3 Apoptosis Cell Biology Caspase 9 Caspases Initiator Cell biology 03 medical and health sciences 0302 clinical medicine 030220 oncology & carcinogenesis Apoptosomes biology.protein Animals Humans Apoptosome Signal transduction Caspase 030304 developmental biology Signal Transduction |
| Zdroj: | Experimental cell research. 318(11) |
| ISSN: | 1090-2422 |
| Popis: | Key structural and catalytic features are conserved across the entire family of cysteine-dependent aspartate-specific proteases (caspases). Of the caspases involved in apoptosis signal transduction, the initiator caspases-2, -8 and -9 are activated at multi-protein activation platforms, and activation is thought to involve homo-dimerisation of the monomeric zymogens. Caspase-9, the essential initiator caspase required for apoptosis signalling through the mitochondrial pathway, is activated on the apoptosome complex, and failure to activate caspase-9 has profound pathophysiological consequences. Here, we review the pertinent literature on which the currently prevalent understanding of caspase-9 activation is based, extend this view by insight obtained from recent structural and kinetic studies on caspase-9 signalling, and describe an emerging model for the regulation of caspase-9 activation and activity that arise from the complexity of multi-protein interactions at the apoptosome. This integrated view allows us to postulate and to discuss functional consequences for caspase-9 activation and apoptosis execution that may take centre stage in future experimental cell research on apoptosis signalling. |
| Databáze: | OpenAIRE |
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