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Physiological role of SIGIRR in early embryonic development.
Hanusová, Zdeňka ; Filipp, Dominik (advisor) ; Brdička, Tomáš (referee)
IL-1 receptor/Toll-like receptor (IL-1R/TLR) supefamily represents a group of proteins that share highly conserved TIR domain in their cytoplasmic region. Signal transduction mediated by TIR-containing proteins involves the activation of NF-κB transcription factor and thus the members of this superfamily play a key role in many physiological responses related to innate immune defense and inflammation. SIGIRR (single immunoglobulin IL1R-related molecule) is a recently discovered member of the IL-1R family, however it differs from the other group members by its unique structural features. SIGIRRhas been so far considered to be an 'orphan' receptor as no SIGIRR ligand has been identified yet. Moreover, SIGIRR itself is not capable to induce the NF-κB activation. Instead, SIGIRR is supposed to act as a negative regulator for IL- 1Rs/TLRs mediated inflammation. Its inhibitory function has been implemented in several signalling pathways in various cell types and tissues including the kidney, the digestive tract and the lung. Recent reports also suggest that SIGIRR could play a role in early embryonic development. The main aim of this thesis is to characterize the mechanism how SIGIRR negative regulatory function in IL-1R/TLR signalling pathway is delivered. Here we describe the establishment of...
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Physiological role of SIGIRR in early embryonic development.
Hanusová, Zdeňka ; Filipp, Dominik (advisor) ; Brdička, Tomáš (referee)
IL-1 receptor/Toll-like receptor (IL-1R/TLR) supefamily represents a group of proteins that share highly conserved TIR domain in their cytoplasmic region. Signal transduction mediated by TIR-containing proteins involves the activation of NF-κB transcription factor and thus the members of this superfamily play a key role in many physiological responses related to innate immune defense and inflammation. SIGIRR (single immunoglobulin IL1R-related molecule) is a recently discovered member of the IL-1R family, however it differs from the other group members by its unique structural features. SIGIRRhas been so far considered to be an 'orphan' receptor as no SIGIRR ligand has been identified yet. Moreover, SIGIRR itself is not capable to induce the NF-κB activation. Instead, SIGIRR is supposed to act as a negative regulator for IL- 1Rs/TLRs mediated inflammation. Its inhibitory function has been implemented in several signalling pathways in various cell types and tissues including the kidney, the digestive tract and the lung. Recent reports also suggest that SIGIRR could play a role in early embryonic development. The main aim of this thesis is to characterize the mechanism how SIGIRR negative regulatory function in IL-1R/TLR signalling pathway is delivered. Here we describe the establishment of...
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The function of palmitoylation of membrane proteins in immune cells
Hanusová, Zdeňka ; Otáhal, Pavel (advisor) ; Pavlů, Barbora (referee)
Protein palmitoylation is a post-translation modification, which typically regulates the protein interaction with a membrane; apart from that, it can have various functions in protein regulation. Process of this modification covers covalent attachment of palmitate to an aminoacid residue in the target protein; identity of the aminoacid than determines the palmitoylation type. Most common is modification of a cystein residue - in that case we speak about so-called S-palmitoiyation. The exceptionality of this lipid modification type is in the reversibility of the whole process; this enables for example trafficking regulation of many proteins between various membrane compartments and ragulation of proteins' function. In vivo, palmitoylation of many proteins is mediated by enzymes protein acyltransferases, while depalmitoylation is mediated by enzymes acylprotein thioesterases. Palmitoylated proteins can be identified in wide spectrum of cellular types, also in immune cells. Palmitoylation plays here an important role, especially in interaction of signal proteins with lipid rafts and the related modulation of protein's function. Significance has palmitoylation also as a dynamic process, which mediates the right identification of protein's subcellular localization. This work is a review and it's aim is...
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