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Role of DD- and DED-containing adaptor proteins in apoptotic signaling
Čaja, Fabián ; Anděra, Ladislav (advisor) ; Janštová, Vanda (referee)
Proteins containing a bundle of six anti-paralel α-helices in so-called "death domain" (DD) and similar structures (DED, CARD) represent important players in apoptotic signaling. To DD/DED/CARD domains-containing proteins belong pro- apoptotic membrane receptors from the TNFR superfamily, then adaptor proteins and enzymes as proteases or kinases. These pro-apoptotic "death receptors" interact with adaptor proteins and initiator caspases containing DDs or DEDs and activate apoptotic signaling cascade. DEDs and DDs are in addition found in many proteins participating in activation of caspases or other non-apoptotic signaling. Many experimental models document that defects in and deregulations of proteins containing DDs and DEDs can have severe if not lethal consequences for an organism. Abberations in these proteins in many cases could lead to cancerogenesis, immunodeficiencies or developmental defects.
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The role of membrane microdomains and transmembrane adaptor proteins PRR7 and SCIMP in the regulation of immunoreceptor signaling
Hrdinka, Matouš ; Drbal, Karel (advisor) ; Černý, Jan (referee) ; Kalina, Tomáš (referee)
Dissertation summary The role of membrane microdomains and transmembrane adaptor proteins PRR7 and SCIMP in the regulation of immunoreceptor signaling Matouš Hrdinka How do the plasma membrane microdomains and transmembrane adaptor proteins (TRAPs) influence the outcome of immunoreceptor signaling? These have been the important questions of molecular immunology. In spite of the years of intensive research, these problems remain incompletely understood. The plasma membrane is a highly dynamic heterogeneous bilayer spontaneously organized into microdomains of various size, composition, and lifetime. The lipid rafts are one example of such microdomains and have been implicated in many biological processes, including immunoreceptor signaling. Because rafts are enriched in many signaling proteins, they are believed to function as platforms for signal initiation and propagation. The TRAPs are important organizers and regulators of immunoreceptor signaling. For example, LAT is indispensable in T cell receptor (TCR) signaling and T cell development, PAG for the regulation of Src family tyrosine kinases (SFKs), and NTAL is a multifunctional negative and positive regulator. The presence of these TRAPs in lipid rafts seems to be crucial for their functions, however, is still a matter of debate. Moreover, other so far...
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The regulation of the ERK signalling pathway by scaffold protein RACK1
Bráborec, Vojtěch ; Vomastek, Tomáš (advisor) ; Filipp, Dominik (referee)
The ERK signalling cascade comprised of protein kinases Raf, MEK and ERK is an evolutionarily conserved member of MAPK family that is activated in response to wide range of extracellular stimuli. The ERK pathway controls fundamental cellular functions including cell proliferation, differentiation, apoptosis or cell motility. To control such a diverse cellular responses by a single pathway cells have evolved regulatory mechanisms that channel the extracellular signals towards the specific biological response. Crucial to this control are non- enzymatic proteins termed scaffolds that associate with and enhance functional interaction of the components of MAPK pathways and can regulate amplitude, timing, specificity and location of signals. Scaffold protein RACK1 associates with several components of cell migration machinery including integrins, FAK, Src and the ERK pathway core protein kinases. RACK1 regulates distinct steps of cell migration such as establishment of cell polarity and focal adhesion turnover, however, the molecular mechanism by which RACK1 regulates these processes remains largely unknown. The main aim of this study was to investigate the functional role of RACK1 in cell motility, in particular to identify new effector proteins utilized by the ERK pathway and RACK1 in the regulation of...
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Role of DD- and DED-containing adaptor proteins in apoptotic signaling
Čaja, Fabián ; Janštová, Vanda (referee) ; Anděra, Ladislav (advisor)
Proteins containing a bundle of six anti-paralel α-helices in so-called "death domain" (DD) and similar structures (DED, CARD) represent important players in apoptotic signaling. To DD/DED/CARD domains-containing proteins belong pro- apoptotic membrane receptors from the TNFR superfamily, then adaptor proteins and enzymes as proteases or kinases. These pro-apoptotic "death receptors" interact with adaptor proteins and initiator caspases containing DDs or DEDs and activate apoptotic signaling cascade. DEDs and DDs are in addition found in many proteins participating in activation of caspases or other non-apoptotic signaling. Many experimental models document that defects in and deregulations of proteins containing DDs and DEDs can have severe if not lethal consequences for an organism. Abberations in these proteins in many cases could lead to cancerogenesis, immunodeficiencies or developmental defects.
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