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Activation of the initiation caspases and regulation of their activity
Votavová, Barbora ; Anděra, Ladislav (advisor) ; Černý, Jan (referee)
Caspases are the key proteins participating in both activation and execution of apoptosis. Extrinsic or intrinsic apoptotic signaling leads to sequential activation of the initiation and execution caspases. Activation of initiator caspases is mediated by their processing in multiprotein complexes and activated initiator caspases then specifically cleave and thus activate the effector caspases. These then cleave a number of structural and functional proteins, which consequently leads to cellular selfdestruction and its breakdown to apoptotic bodies. Considering the fundamental significance of the initiation of apoptosis, the activation as well as the activity of initiator (but also effector) caspases is strictly regulated at several levels. Primary the intensity and character of the recieved signal is crucial for the effective formation of the caspase activation complex. Then the concentration of intracellular ionts, nucleotides and various proteins (proteins from the Bcl-2 family, inhibitors of apoptosis (IAPs), heat shock proteins,…) can also highly influence individual steps of caspase activation. Caspases themself can be posttranslationally modified (phosphorylated, ubiquitylated,…) and their activity can be either suppressed or also enhanced. All these processes form complex regulatory network serving...

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