Search results for "Transcription"
showing 10 items of 2278 documents
DRB1*0401-restricted human T cell clone specific for the major proinsulin73-90 epitope expresses a down-regulatory T helper 2 phenotype.
2006
Recently, we have identified proinsulin (P-Ins) 73-90 as an immunodominant T cell epitope of HLA-DRB1*0401 (DR4) subjects with β-islet cell autoimmunity and of HLA-DR4/CD4 double-transgenic mice immunized with human P-Ins. We have compared the fine specificities of one human CD4 T cell clone and two mouse T cell hybridoma clones recognizing this epitope, and, although these three clones all recognized the same core region (LALEGSLQK), there were major differences in how they interacted with the peptide (p)/HLA complex, reflecting the fact that human P-Ins is a foreign antigen in the mouse and an autoantigen in the type 1 diabetes patient. The human T cell clone was forkhead transcription f…
The ubiquitin-specific protease USP8 is critical for the development and homeostasis of T cells
2015
The modification of proteins by ubiquitin has a major role in cells of the immune system and is counteracted by various deubiquitinating enzymes (DUBs) with poorly defined functions. Here we identified the ubiquitin-specific protease USP8 as a regulatory component of the T cell antigen receptor (TCR) signalosome that interacted with the adaptor Gads and the regulatory molecule 14-3-3β. Caspase-dependent processing of USP8 occurred after stimulation of the TCR. T cell-specific deletion of USP8 in mice revealed that USP8 was essential for thymocyte maturation and upregulation of the gene encoding the cytokine receptor IL-7Rα mediated by the transcription factor Foxo1. Mice with T cell-specifi…
Accelerated evolution of a minimal 63–amino acid dual transcription factor
2020
Transcription factors control gene expression in all life. This raises the question of what is the smallest protein that can support such activity. In nature, Cro from bacteriophage λ is one of the smallest known repressors (66 amino acids), and activators are typically much larger (e.g., λ cI, 237 amino acids). Previous efforts to engineer a minimal activator from λ Cro resulted in no activity in vivo in cells. In this study, we show that directed evolution results in a new Cro activator-repressor that functions as efficiently as λ cI in vivo. To achieve this, we develop phagemid-assisted continuous evolution (PACEmid). We find that a peptide as small as 63 amino acids functions efficientl…
Early stress response of human nasal respiratory epithelia after exposure to 1-methoxypropanol-2
2007
To evaluate the impact of 1-methoxypropanol-2 (MEP) for the stimulation of an inflammatory response in human respiratory mucosa, we exposed 22 primary cell cultures of nasal respiratory epithelia of healthy individuals to MEP concentrations at the level of the German MAK-value (100 ppm) and to the 10-fold concentration (1000 ppm). After 4 and 24h we analyzed the transcription of TNF-alpha, IL-1beta, IL-6, IL-8, MCP-1, GMCSF, Cox-1 and Cox-2 by quantitative PCR as well as the release of the respective cytokines by ELISA. At both MEP concentrations we observed a significant increase of TNF-alpha-, IL-1beta-, IL-6- and Cox-2-transcripts after 4h. After 24h cytokine transcription of TNF-alpha, …
The peroxisome proliferator response element (PPRE) present at positions -681/-669 in the rat liver 3-ketoacyl-CoA thiolase B gene functionally inter…
2000
Although previous data showed that the putative thiolase B PPRE located at -681/-669 bind the PPARalpha-RXRalpha heterodimer in vitro (Kliewer et al. (1992) Nature 358, 771-774), there is no evidence about the functional role of this element. By gel mobility-shift assay, we found an interaction of this PPRE with not only PPARalpha but also with HNF-4. By transfection of cells with the putative PPRE-driven luciferase reporter vector and PPARalpha, we found no significant activation of the luciferase gene expression, in contrast to the case with reporter expression driven by the PPRE of the peroxisomal bifunctional enzyme. On the other hand, HNF-4 activated the luciferase gene expression driv…
In situ localization of the Antennapedia gene on the chromosomes of nine Drosophila species of the obscura group.
2008
The homeotic Antennapedia gene, cloned from the genomic DNA of D. subobscura, was localized on the polytene chromosomes of nine species of the Drosophila obscura group. In all of them, the probe used hybridized on chromosomes equivalent to the E element of Muller's terminology. These results are consistent with the idea that single copy genes do not move around the genome and that chromosomal elements have conserved their genetic identity during evolution.
Connecting temporal identity to mitosis: the regulation of Hunchback in Drosophila neuroblast lineages.
2006
Both in vertebrates and invertebrates, neural stem cells generate different cell types at different times during development. It has been suggested that this process depends on temporal identity transitions of neural progenitors, but the underlying mechanism has not been resolved, yet. Recently, Drosophila neuroblasts (NBs) have been shown to be an excellent model system to investigate this subject. Here, changes in temporal identity are regulated by sequential and transient expression of transcription factors in the NB, such as Hunchback (Hb) and Kruppel (Kr). The temporal expression profile is maintained in the progeny. Hb is expressed first and thus defines the earliest identity in a giv…
PGC-1α signaling coordinates susceptibility to metabolic and oxidative injury in the inner retina.
2013
Retinal ganglion cells (RGCs), used as a common model of central nervous system injury, are particularly vulnerable to metabolic and oxidative damage. However, molecular mechanisms underlying this sensitivity have not been determined in vivo . PGC-1α (encoded by PPARGC1A ) regulates adaptive metabolism and oxidative stress responses in a tissue- and cell-specific manner. Aberrant PGC-1α signaling is implicated in neurodegeneration, but the mechanism underlying its role in central nervous system injury remains unclear. We provide evidence from a mouse model that PGC-1α expression and activity are induced in adult retina in response to metabolic and oxidative challenge. Deletion of Ppargc1a d…
Molecular genetics of autosomal dominant retinitis pigmentosa (ADRP): a comprehensive study of 43 Italian families
2005
Retinitis pigmentosa is the most common form of retinal degeneration and is heterogeneous both clinically and genetically. The autosomal dominant forms ( ADRP) can be caused by mutations in 12 different genes. This report describes the first simultaneous mutation analysis of all the known ADRP genes in the same population, represented by 43 Italian families. This analysis allowed the identification of causative mutations in 12 of the families (28% of the total). Seven different mutations were identified, two of which are novel (458delC and 6901C --> T (P2301S), in the CRX and PRPF8 genes, respectively). Several novel polymorphisms leading to amino acid changes in the FSCN2, NRL, IMPDH1, and…
Differential display reverse transcription PCR reveals IL-1 induced gene expression patterns in human articular chondrocytes
1995
IL-1 exerts diverse effects on the metabolism of articular chondrocytes, including inhibition of proteoglycan synthesis and stimulation of matrix metallopro teinase synthesis. Therefore it is believed that IL-1 might play an important role in cartilage degradation in osteo- and rheumatoid arthritis. To improve our understanding of IL-1 induced effects on overall gene expression patterns of human articular chondrocytes, wc used a novel mRNA fingerprinting technique: Differential Display Reverse Transcription-PCR (DDRT-PCR) (Liang and Pardee 1992). The reported high sensitivity of this powerful technique promised to enable work with human articular cartilage, a tissue from which only small am…