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Role of tumour suppressor PML in nucleolar functions
Kučerová, Alena ; Hodný, Zdeněk (advisor) ; Stejskalová, Eva (referee)
The cell nucleus is a complex structure composed of different parts, the nucleolus and PML nuclear bodies are important compartments of the nucleus. In the nucleolus, transcription of ribosomal DNA and biogenesis of ribosomes take place. The nucleolus may regulate the expression of proteins and thus the subsequent cell growth through regulating the amount of ribosomes. The nucleolus is also a sensor of stress. PML nuclear bodies play an important role in many cellular process - response to stress, virus infection or DNA damage. PML nuclear bodies consist of many proteins, the major protein is PML protein (Promyelotic leukemia protein). PML protein is coded by PML gene, it is spliced postrancriptionally and it has several isoforms. PML protein is an important cellular regulator and also a tumor suppressor. The nucleolus and PML protein cooperate together and have a functional relationship, which is not entirely clear. It was shown that PML protein changes its localization after exposure to stress and it goes near the nucleolus or into the nucleolus and this happens mainly in primary cells (the reason can be that the level of PML protein downregulates in tumour cells). The relationship between the nucleolus and PML nuclear bodies is important for cell response to stress. Keywords: nucleolus,...
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The role of PML nuclear bodies in herpesvirus infection
Bártová, Jana ; Šroller, Vojtěch (advisor) ; Saláková, Martina (referee)
PML nuclear bodies are protein structures in the cell nucleus that regulate many important cellular processes and are also implicated in antiviral defense. The permanent components of these nuclear bodies include PML, Sp100 and Daxx proteins, many other proteins are transiently associated with PML bodies. PML body components can be SUMOylated, this posttranslational modification is important for the formation of PML bodies and regulation of their function. Components of PML bodies such as PML, Sp100 and Daxx can act as restriction factors limiting the replication of many DNA and RNA viruses. Defense mechanisms mediated by PML bodies are suppressed by viral proteins that inactivate individual components or disrupt the structure of PML bodies. This thesis focuses on the role of PML bodies as restriction factors during infection by DNA viruses of the Herpesviridae family and describes the interactions of PML bodies and viral proteins, using herpes simplex virus 1, human cytomegalovirus and Epstein-Barr virus as examples. Keywords: PML nuclear bodies, restriction factor, antiviral defense, innate immunity, herpesviruses
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Role of tumour suppressor PML in nucleolar functions
Kučerová, Alena ; Hodný, Zdeněk (advisor) ; Stejskalová, Eva (referee)
The cell nucleus is a complex structure composed of different parts, the nucleolus and PML nuclear bodies are important compartments of the nucleus. In the nucleolus, transcription of ribosomal DNA and biogenesis of ribosomes take place. The nucleolus may regulate the expression of proteins and thus the subsequent cell growth through regulating the amount of ribosomes. The nucleolus is also a sensor of stress. PML nuclear bodies play an important role in many cellular process - response to stress, virus infection or DNA damage. PML nuclear bodies consist of many proteins, the major protein is PML protein (Promyelotic leukemia protein). PML protein is coded by PML gene, it is spliced postrancriptionally and it has several isoforms. PML protein is an important cellular regulator and also a tumor suppressor. The nucleolus and PML protein cooperate together and have a functional relationship, which is not entirely clear. It was shown that PML protein changes its localization after exposure to stress and it goes near the nucleolus or into the nucleolus and this happens mainly in primary cells (the reason can be that the level of PML protein downregulates in tumour cells). The relationship between the nucleolus and PML nuclear bodies is important for cell response to stress. Keywords: nucleolus,...
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Role of the tumour suppressor PML in DNA damage response and cellular senescence after genotoxic stress
Knoblochová, Lucie ; Hodný, Zdeněk (advisor) ; Horníková, Lenka (referee)
The promyelocytic leukemia protein (PML) is a tumour suppressor. It has been reported that PML interaction with the p53 protein is involved in the activation of cell cycle checkpoints and, when persistent, may lead to the premature onset of cellular senescence. Cellular senescence is a state of permanent cell growth arrest that is associated with characteristic morphological and metabolic changes and persistent DNA damage signalling. Importantly, PML nuclear bodies coassociate with persistent DNA damage foci in senescent cells; however, the role of this interaction is still obscure. My goal was to characterize the role of PML in DNA damage response (DDR) and the induction of premature cellular senescence after genotoxic stress, namely X-radiation, using both siRNA-mediated PML knock down (PML KD) and complete PML knock out (PML KO) in human cells. The dynamics of DNA damage foci, levels of various proteins involved in DDR, and proliferation rate were measured in both PML KD and KO cells. No significant changes in the formation of DNA damage foci, activated DDR (p53 and Chk2), activated p21CIP1/WAF1 cyclin-dependent kinase inhibitor, senescent morphology, and SA-β-galactosidase activity in PML KO cells were observed. However, PML KO cells displayed higher levels of retinoblastoma protein (Rb) and...
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