National Repository of Grey Literature 35 records found  1 - 10nextend  jump to record: Search took 0.00 seconds. 
Promyelocytic leukemia protein function in normal, tumor and senescent human cells
Rossmeislová, Lenka ; Hozák, Pavel (advisor) ; Forstová, Jitka (referee) ; Anděra, Ladislav (referee)
Promyelocytic leukemia protein (PML) gene encodes a nuclear protein localizing into the nucleoplasm and distinct nuclear bodies, referred to as PML nuclear bodies (PML NBs). PML is now considered as a gene with tumor-suppressive properties since it is implicated in many nuclear functions affecting cellular proliferation, apoptosis and senescence. The presented work is a part of a larger project that aims to clarify the regulation of promyelocytic leukemia protein expression and investigates the role of PML protein in cellular senescence. The specific goals of my PhD project were to evaluate new in vitro models for the study of PML, to elucidate the effects of histone deacetylase inhibitors on PML gene expression, and to investigate the association of PML with the nucleolus.
Localization matters: function of paxillin and phopholipids in the cell nucleus
Marášek, Pavel ; Hozák, Pavel (advisor) ; Půta, František (referee) ; Žárský, Viktor (referee)
(English) Both paxillin and PIP2 are well known components of the cell, although of a distinct origin. Focal adhesion protein paxillin spreads the signals from extracellular matrix via integrins and growth factor receptors to affect cellular motility and migration (Schaller, 2001). PIP2, a major structural component of cytoplasmic membrane, is utilized by phospholipase C to generate second messenger molecules (Hokin and Hokin 1953; Streb et al. 1983). Both molecules were recently shown to be localized in the nucleus. Their original functions have been well established, but together with other research colleagues we are now shedding more light on completely different functions of these biological molecules and moreover, in the different compartments than they were primarily believed to function in. Here, we introduce paxillin as an important factor of the cell nucleus, where it regulates transcription of two important growth-related genes, IGF2 and H19. It does not affect the allelic expression of these imprinted genes, it rather regulates long-range chromosomal interactions between H19 or IGF2 promoter, and the shared distal enhacer on an active allele. In detail, paxillin stimulates the interaction between the enhancer and the IGF2 promoter, activating IGF2 gene transcription, while it restrains...
Manipulating the mammalian oocyte and embryo - Biological and epigenetic aspects
Fulková, Helena ; Hozák, Pavel (advisor) ; Hampl, Aleš (referee) ; Motlík, Jan (referee)
CONCLUSIONS . By antibodies against ďfferent covalent histone modifications and 5-methylcytosine, we have partialty characterised the epigenetic changes taking place during the oocyte mauration and in early mammalian embryogenesis in the mouse and pig, respectively. o We have also characterised thc epigenetic repogramming activities of cytoplasts derived from oocytes at different stages of maturation after somatic cell nuclear transfer. . We have evaluated the epigenetic effec$ of selected procedures that are currently used for embryo production. . Finally, we have developed a new cryopreservation scheme for oocyte nuclear material storage. orrr research is engaged in the development ofnew bíotechniques as well as elucidating and characterising the epigenetic pÍocesses that take place during normal and abnormal embryogenesis. Abnormal embryonic development is for example often observed in somatic cell nuclear transfer embryos. These techniques can also be potentially used not only in human medicine but also for valuable livestock and endangered species preservation Oy e.g. interspecies nuclear transfer). Especially in human meďcine, attention to the ethical issues associated with these techniques must be paid. It is also clear tbat many biological problems still do exist and these should not be...
Myosin I and actin binding proteins in cell
Krásna, Hana ; Hozák, Pavel (advisor) ; Motlík, Jan (referee) ; Pěknicová, Jana (referee)
Many studies have established the presence and essenciality of actin in the nucleus. Recently, actin has been associated with processes in the nucleus ranging from chromatin remodeling to transcription, splicing or nuclear transport. To ensure the dynamics of the nuclear processes, actin is coupled with one of the main motor protein such as myosin. This study demonstrates a structural role of actin and the nuclear myosin I (NMI) take in the transcription of ribonuclear genes by RNA polymerase I (Pol l). We suppressed the transcription Pol I in vitro by microinjections of antibodies anti actin and anti MNI. The series of in vitro experiments confirm transcript Pol I inhibition after applying antibodies anti actin and MNI on pure DNA as well as on pre-assembled chromatine template. The co-immunoprecipitation experiments reveal direct bound between actin, NMI and rRNA genes and transcription complex Pol I. As actin binds to the primer and elonged Pol I molecule, NMI interacts with subunit of Pol I and is capable of assembling into productive initiation complex by binding up to TIF-IA, transcriptional factor responsible for regulation rRNA synthesis. There are known number of hypothesis on the form of nuclear actin. Recent research suggests actin exists in equilibrium between its monomeric and...
Analysis of functional interactions of phospholipids in the cell nucleus.
Biddle, Veronika ; Hozák, Pavel (advisor) ; Kaňka, Jiří (referee) ; Malínský, Jan (referee)
(English) Phosphoinositides (PIs) are glycerophospholipids with a negative charge. As components of cell membranes, PIs are involved in membrane and cytoskeletal dynamics, cell movement and signalling, and the modulation of ion channels and transporters. Apart from the cytoplasm, phosphoinositides also localise to the cell nucleus. PIs play a role in crucial nuclear processes, such as DNA transcription, pre-rRNA and pre-mRNA processing, cell differentiation, DNA damage response, or apoptosis. Phosphatidylinositol 4-phosphate (PI(4)P) and phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) are the most abundant phosphoinositides in the cell. However, their exact localisation and function in the nucleus are largely unknown. Here, we describe their localisation at super-resolution level and their involvement in some nuclear processes. PI(4)P is present in nuclear lamina, nuclear speckles and nucleoli, and it forms small foci in nucleoplasm. The majority of nuclear PI(4)P localises to the nucleoplasm, whereas almost 16 % is present in nuclear speckles. On the other hand, the majority of nuclear PI(4,5)P2 localises to nuclear speckles, almost 30 % localises to nucleoplasm and the lesser portion to nucleoli. In the nucleoplasm, PI(4,5)P2 forms small foci called nuclear lipid islets (NLIs). Their core is...
Involvement of protein vinculin in mammalian gametogenesis
Darášová, Alžběta ; Hozák, Pavel (advisor) ; Kaňka, Jiří (referee)
One of the basic characteristics of living systems is a sexual reproduction, when the germ cells, sperm and egg, fuse. The key process in the germ cells development is meiosis. During meiotic division, several dramatic changes happen in the nucleus and different errors might appear, which may then result in various chromosomal aberrations and nondisjunctions leading to genetic diseases and infertility. The causes of infertility are very diverse, but many of them obviously come from the meiotic errors. One of the most critical parts for the successful meiotic progress is a prophase I, where the homologous chromosomes are paired by the protein structure of the synaptonemal complex (SC) and subsequent genetic recombinations by crossing- over accurate. Vinculin (VCL) is a cytoplasmic actin binding protein in the focal adhesions and adherent junctions and VCL acts as their essential regulator. Recently, this protein was also found in the nucleus of germ cells of certain organisms. However, the nuclear functions of vinculin have not been described yet. This diploma thesis focuses on the study of chromosomal dynamics in the gametogenesis of our mouse model, regarding the involvement of the nuclear vinculin in these processes. Our aim was to localize VCL in the nucleus of embryonic prophase oocytes using...
Function of nuclear phosphoinositides and their binding partners in gene expression
Uličná, Lívia ; Hozák, Pavel (advisor) ; Šolc, Petr (referee) ; Macůrková, Marie (referee)
(ENGLISH) Phosphoinositides (PIs) are negatively charged glycerol-based phospholipids with inositol head (ring) which can be phosphorylated. Inositol ring phosphorylation yields in seven different PIs species which can be mono-, bis,- or tris-phosphorylated. Roles of cytoplasmic PIs have been extensively studied in for membrane and cytoskeletal dynamics, vesicular trafficking, ion channels and transporters and generating of second messengers. Nuclear PIs have been implicated in posttranscriptional processing of pre-mRNA, DNA transcription and chromatin remodelling. While cytoplasmic functions are very well described, the molecular mechanism of their nuclear functions are still poorly understood. In this study we focus on description of localization of nuclear PIs in particular functional nuclear compartments, which enable us to reveal PIs involvement in nuclear processes. We also focused on identification of nuclear PIs involved in the regulation of genes transcription and revealed detailed mechanism of PI(4,5)P2 a PHF8 interaction in the regulation of ribosomal genes transcription. By two independent approaches, we have described PIs localization to the nuclear membrane, nuclear speckles, small foci in the nucleoplasm, and the nucleolus. This spread nuclear localization suggests and confirms PI's...

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