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Activation and function of BH3-only proteins from the Bcl-2 family
Peterka, Martin ; Anděra, Ladislav (advisor) ; Pavlů, Barbora (referee)
The Bcl-2 (B-cell lymphoma-2) family of proteins comprises crucial regulators of apoptosis in metazoans. In mammals, Bcl-2 family members regulate mitochondrial outer membrane permeabilization (MOMP), which leads to the release of pro-apoptotic molecules from the mitochondrial intermembrane space and subsequent apoptosis. Defects in the Bcl-2 signaling can result in various pathological conditions including cancer. BH3-only proteins form a pro-apoptotic subset of the Bcl-2 family. They mainly act as sensors of various pro-apoptotic stimuli such as cytokine deprivation, genotoxic stress, activated "death receptors" and others. In mammals, over ten BH3-only proteins have been identified, eight of which have been linked to the regulation of MOMP. These "conventional" BH3-only proteins are Bim, Bid, Puma, Noxa, Bad, Hrk, Bik and Bmf. This thesis provides an overview of their origin, structure, activation and involvement in apoptosis.
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