Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.1.21 (thymidine kinase)
 7,561 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Vimentin is one member of the intermediate filament multigene family which exhibits both tissue- and developmental stage-specific expression. In vivo, vimentin is expressed in cells of mesenchymal origin. Previously, we identified both enhancer and promoter elements in the chicken vimentin gene which regulate gene expression in a positive manner. In this report, we have identified a 40-base-pair region at -568 base pairs between the proximal and distal enhancer elements which represses transcriptional activity. This silencer region can also repress the heterologous herpes simplex virus thymidine kinase promoter, which is comparable to the vimentin promoter. In addition, the element is able to function in a position- and orientation-independent manner, and the amount of repression is increased by multiple copies. Here we show by gel retardation assays and DNase I footprinting that this region binds a protein in nuclear extracts from HeLa cells. Southwestern (DNA-protein) blot analysis indicates this protein is approximately 95 kilodaltons in size. Moreover, protein distribution and activity mimic the expression pattern of vimentin during myogenesis, i.e., protein binding increases as vimentin gene expression decreases. The silencer region shares strong sequence similarity with 5'-flanking sequences found in both the human and hamster vimentin genes and with other characterized silencer elements, including the human immunodeficiency virus long terminal repeat, rat growth hormone, chicken lysozyme, and rat insulin genes. Thus, a negative element appears to bind a 95-kilodalton protein involved in regulating the tissue-specific expression of the chicken vimentin gene.
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PMID:A negative element involved in vimentin gene expression. 232 56

Somatic cell hybrids were obtained with electric pulse by fusion of human epithelial HeLa cells derived from a carcinoma of the uterine cervix and mouse fibroblasts 3T3.4E, deficient in thymidine kinase. Hybrids were selected and propagated in HAT media; some experiments were carried out in medium with delipidized serum. The hybrid cells were characterized by indirect immunofluorescence with a biotin-streptavidin system using a panel of nine monoclonal antibodies specific for membrane and cytoplasmic antigens of parental cells: intermediate filaments (keratins and vimentin), HLA class 1 (beta 2-microglobulin), cell activation (EGF and transferrin receptors) and cellular adhesion (fibronectin and laminin). All of these antigens were expressed in HeLa cells cultured in conventional medium or with delipidized serum. Conversely mouse fibroblasts contained only vimentin, fibronectin and laminin. All the parental antigens were present in first passage hybrid cells cultured in conventional medium. Vimentin, fibronectin and laminin were maintained in fourth passage hybrids whereas keratins, beta 2-microglobulin, EGF and transferrin receptors were no longer detected. When propagated in medium with delipidized serum, hybrid cells re-expressed these antigens after 5 days of culture. These findings suggest that the reexpression of HeLa cell antigens in hybrid cells was related to deficiency in vitamin A.
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PMID:Antigenic immunostaining patterns in somatic hybrids of human HeLa cells and mouse fibroblasts 3T3.4E propagated in conventional medium and delipidized serum. 248

The neurogenic niche of the subventricular zone (SVZ) in adult brain tissue takes the form of a pinwheel-like cytoarchitectural structure, with mono-ciliated astrocytes displaying neural stem cell (NSC) characteristics present in the core surrounded by ciliated ependymal cells. For the first time, we have demonstrated the formation of similar pinwheel structures in spinal cord and SVZ tissue-derived neurospheres cultured in vitro. To investigate whether the organization and integrity of these pinwheel structures depends on the appropriate organization of ciliated astrocytes and ependymal cells, we modified neurosphere cell arrangements via the application of the methyltransferase inhibitor 5-aza-2'-deoxycytidine (5-aza-dc) or the antiviral drug ganciclovir (GCV) in transgenic mice expressing herpes simplex virus thymidine kinase from the GFAP promoter (GFAP-TK). Treatment of neurospheres with 5-aza-dc increased FoxJ1 expression, a crucial factor for ciliogenesis, by reducing methylation of the FoxJ1 CpG island. 5-aza-dc also increased the expression of the astrocyte marker GFAP and caused aberrant accumulation of ciliated astrocytes. However, the ablation of dividing astrocytes within neurospheres by GCV treatment led to an increase in the accumulation of ciliated ependymal cells, as evidenced by the increased expression of the ependymal cell markers Vimentin or CD24. While 5-aza-dc and GCV treatment differentially affected cell arrangement, both compounds significantly diminished the number of pinwheel structures present in neurospheres. Thus, we suggest that the ratio of ciliated astrocytes to ependymal cells plays a crucial role in the correct formation of the pinwheel structures in spinal cord tissue-derived neurospheres in vitro.
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PMID:Organized Neurogenic-Niche-Like Pinwheel Structures Discovered in Spinal Cord Tissue-Derived Neurospheres. 3192 46