89 research outputs found
Phosphatidylserine exposure by apoptotic cells:a phylogenetically conserved mechanism
No full textTolerance of the existence of the individual cell in multicellular organisms is mediated by the distribution of the various phospholipid species across the bilayer of the plasma membrane. This concept arises from in vitro studies, which show that cellsurface exposed phosphatidylserine on ageing erythrocytes and apoptotic leukocytes triggers elimination of these cells by phagocytosis. In contrast, blood cells are inert in this respect when this aminophospholipid is predominantly residing in the plasma membrane leaflet facing the cytoplasm. We have studied the in vivo distribution of cell surface-exposed phosphatidylserine by injecting biotinylated AnxV, a Ca2+dependent phosphatidylserine binding protein, into viabIe mouse and chick embryos and Drosophila pupae. The apparent binding of (Annexin V) to cells that were present in regions of developmental cell death and that were exhibiting the morphology which is characteristic of apoptosis indicates that phosphatidylserine exposure by apoptotic cells is a phylogenetically conserved mechanism
Structural diversity of frameshifting signals : reprogramming the programmed
No full textProgrammed ribosomal frameshifting (PRF) is one kind of recoding events that is mostly utilized by RNA viruses to synthesize more proteins with defined ratio from their compact genome and it is known that the stoichiometric is critical to virus infection and propagation. Two cis-acting RNA elements are critical to induce PRF: one is slippery sequence where the frameshifting occurs and the other is RNA secondary structure, either a stem-loop or pseudoknot, to stall ribosomes on the slip site. In this thesis, we first demonstrate that a stem-loop structure can efficient replace pseudoknot in inducing frameshifting, arguing previous assumption hairpins are efficient frameshiftors. Furthermore, we show antisense oligonucleotides (AON) that mimic hairpin or pseudoknot can promote efficient frameshifting suggesting the downstream secondary structures act as physical barriers in frameshifting. Finally, we report a novel ligand responsive frameshifting signal derived from non-frameshifting preQ1 riboswitch aptamer. This interesting finding may have potential to select compounds with anti-bacteria ability. In sum, we successfully use in trans AONs or metabolites to induce PRF. These findings not only address fundamental mechanism of PRF but have potential to develop drugs against frameshifting diseases or bacteria.UBL - phd migration 201
Apoptin : oncogenic transformation & tumor-selective apoptosis
No full textCancer is one of the leading causes of death worldwide. Treatment is hampered by an incomplete understanding of the mechanisms underlying carcinogenesis and, consequently, by the absence of therapies to specifically eradicate cancer cells without harming normal, healthy cells. Intriguingly, the avian-virus derived protein apoptin was found to selectively induce apoptosis in transformed and tumor cells, heralding the advent of a new era in cancer treatment. The aim of this thesis was to discover the path followed by apoptin to distinguish between normal and cancer cells, and selectively kill the latter, in order to a) get to the root of the problem that is cancer, and b) provide the knowledge which is necessary to design novel, more selective, more effective, safe anti-tumor therapies. To this end, we identified a number of apoptin-interacting proteins, and studied their roles in tumor-selective apoptin-induced apoptosis.ORCO Bank Curacao; Fundashon Bon Intenshon (Curacao); Maduro & Curiel's Bank Curacao; Seguros Willems (Curacao)UBL - phd migration 201
Cancer-related targets sensed by apoptin
No full textCancer is one of the most life-threatening diseases worldwide. Many anticancer treatments fail because they are not efficient or reveal too high side effects. Cancer cells develop due to unbalances in cell proliferation, cell cycle regulation and/or cell death. Identification of these aberrant molecular processes will reveal the essential processes leading to tumor formation and allows the generation of potential novel anticancer therapies. Interestingly, a group of viral and cellular proteins has been identified that harbors tumor-selective apoptosis activity. They are named Proteins Killing Tumor Cells (PKTCs). The aim of this thesis is to search for cellular processes sensed by the original PKTC, apoptin, which distinguish tumor cells from normal cells. Various tumor-related processes that are of importance for the tumor-selective activation of apoptin are reported. They range from proteasome activity and mitotic regulation to protein kinase and phosphatase action. The systematic analysis of both apoptin and other PKTCs reflects various differences between normal and tumor cells. Linking-up the various hallmarks of cancer with the aberrant processes sensed by apoptin and other PKTCs in cancer cells will hopefully contribute to a better understanding of tumor development as well as the generation of efficient and safe anticancer therapies.UBL - phd migration 201
Phosphatidylserine exposure by apoptotic cells:a phylogenetically conserved mechanism
No full textTolerance of the existence of the individual cell in multicellular organisms is mediated by the distribution of the various phospholipid species across the bilayer of the plasma membrane. This concept arises from in vitro studies, which show that cellsurface exposed phosphatidylserine on ageing erythrocytes and apoptotic leukocytes triggers elimination of these cells by phagocytosis. In contrast, blood cells are inert in this respect when this aminophospholipid is predominantly residing in the plasma membrane leaflet facing the cytoplasm. We have studied the in vivo distribution of cell surface-exposed phosphatidylserine by injecting biotinylated AnxV, a Ca2+dependent phosphatidylserine binding protein, into viabIe mouse and chick embryos and Drosophila pupae. The apparent binding of (Annexin V) to cells that were present in regions of developmental cell death and that were exhibiting the morphology which is characteristic of apoptosis indicates that phosphatidylserine exposure by apoptotic cells is a phylogenetically conserved mechanism
Phosphatidylserine exposure by apoptotic cells:a phylogenetically conserved mechanism
No full textTolerance of the existence of the individual cell in multicellular organisms is mediated by the distribution of the various phospholipid species across the bilayer of the plasma membrane. This concept arises from in vitro studies, which show that cellsurface exposed phosphatidylserine on ageing erythrocytes and apoptotic leukocytes triggers elimination of these cells by phagocytosis. In contrast, blood cells are inert in this respect when this aminophospholipid is predominantly residing in the plasma membrane leaflet facing the cytoplasm. We have studied the in vivo distribution of cell surface-exposed phosphatidylserine by injecting biotinylated AnxV, a Ca2+dependent phosphatidylserine binding protein, into viabIe mouse and chick embryos and Drosophila pupae. The apparent binding of (Annexin V) to cells that were present in regions of developmental cell death and that were exhibiting the morphology which is characteristic of apoptosis indicates that phosphatidylserine exposure by apoptotic cells is a phylogenetically conserved mechanism
Viral elements inducing tumor-related apoptosis
No full textIn 1997, Danen-Van Oorschot et al. described for the first time that apoptin, a protein encoded by an avian virus, induces p53-independent apoptosis in a tumor-specific way. Various pre-clinical studies in animal tumor models have demonstrated apoptin as a safe and efficient anti-tumor agent. In tumor cells, apoptin is imported into the nucleus prior to the induction of apoptosis and regulated by a kinase activity specifically present in cancer cells. In this thesis, several studies have been carried out to reveal the novel aspects of the molecular pathways underlying the transformation-related apoptosis induction by the viral protein apoptin.UBL - phd migration 201
- …
