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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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Histone deacetylase inhibitors induced caspase-independent cell death
Groh, Tomáš ; Poljaková, Jitka (advisor) ; Eckschlager, Tomáš (referee)
Neuroblastoma is the most common extracranial solid tumor that occurs during infancy. Despite the great progress has been made in contemporary clinic medicine some forms of neuroblastoma disease are still found very difficult to treat . This work focuses on the effects of histone deacetylase inhibitors (HDAC) in the neuroblastoma cell lines. It is known that HDAC inhibitors may contribute to recurrence of the tumor cells by affecting the chromatin structure and thus increase the expression of critical tumor suppressor genes. These genes activate apoptotic pathways that may even be independent of caspases. We observed the efficiency of used HDAC inhibitors as under standard conditions an in hypoxia (1 % O2). Inadequate amount of oxygen supply is one of the characteristic features of tumors and it also may contribute to chemoresistance. With the hypoxia-induced chemoresistance of tumor cells, the influence of HIF-1α is expected. Some HDAC inhibitors reduce the amount of HIF-1α in hypoxia and thus HIF transcription factor activity. Thus, the first part of this study is concerned with the acquisition of suitable experimental arrangement for the monitoring of induction of cellular death in human neuroblastoma cell lines SK-N-AS and UKF-NB-3. Secondly, this paper provides the evaluation of the influence...
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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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