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Cytochrome c and its role in apoptosis
Rajsiglová, Lenka ; Kalous, Martin (advisor) ; Švadlenka, Jan (referee)
Cell energetic metabolism and cell survival are strictly controlled by pathways in which cytochrome molecules play a central role, in particular cytochrome c. It is localized in the mitochondrial intermembrane space with other molecules cooperating in keeping energetic metabolism. Permeabilization of outer mitochondrial membrane by proteins from Bcl-2 family or changes in Ca2+ levels causes cytochrome c release into cytosol. In cytosol cytochrome c interacts with other pro-apoptotic proteins (Apaf-1, procaspase-9) cooperating to form apoptosome and phosphatidylserine. As a result of these interactions, the cell is going to apoptosis. This bachelor thesis summarizes the current state of knowledge of these processes. In the first part it focuses on the biosynthesis of cytochrome c, further on the mechanisms of its releasing from mitochondria and its interactions with other proteins within apoptosis including options of regulation of these processes.
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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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Cytochrome c and its role in apoptosis
Rajsiglová, Lenka ; Kalous, Martin (advisor) ; Švadlenka, Jan (referee)
Cell energetic metabolism and cell survival are strictly controlled by pathways in which cytochrome molecules play a central role, in particular cytochrome c. It is localized in the mitochondrial intermembrane space with other molecules cooperating in keeping energetic metabolism. Permeabilization of outer mitochondrial membrane by proteins from Bcl-2 family or changes in Ca2+ levels causes cytochrome c release into cytosol. In cytosol cytochrome c interacts with other pro-apoptotic proteins (Apaf-1, procaspase-9) cooperating to form apoptosome and phosphatidylserine. As a result of these interactions, the cell is going to apoptosis. This bachelor thesis summarizes the current state of knowledge of these processes. In the first part it focuses on the biosynthesis of cytochrome c, further on the mechanisms of its releasing from mitochondria and its interactions with other proteins within apoptosis including options of regulation of these processes.
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