Search results for "Transcription"
showing 10 items of 2278 documents
Induction of tolerogenic lung CD4+ T cells by local treatment with a pSTAT-3 and pSTAT-5 inhibitor ameliorated experimental allergic asthma.
2010
Signal transducer and activator of transcription (STAT)-3 inhibitors play an important role in regulating immune responses. Galiellalactone (GL) is a fungal secondary metabolite known to interfere with the binding of phosphorylated signal transducer and activator of transcription (pSTAT)-3 as well of pSTAT-6 dimers to their target DNA in vitro. Intra nasal delivery of 50 μg GL into the lung of naive Balb/c mice induced FoxP3 expression locally and IL-10 production and IL-12p40 in RNA expression in the airways in vivo. In a murine model of allergic asthma, GL significantly suppressed the cardinal features of asthma, such as airway hyperresponsiveness, eosinophilia and mucus production, after…
The interleukin-22/STAT3 pathway potentiates expression of inducible nitric-oxide synthase in human colon carcinoma cells.
2007
Inducible nitric-oxide synthase (iNOS) has been identified as a marker and mediator of disease in human colonic inflammation and carcinogenesis. Accordingly, identification of mediators that trigger iNOS in colon carcinoma/epithelial cells is an important topic of current research. Here we demonstrate that interleukin (IL)-22, a newly described member of the IL-10 cytokine family, potently synergizes with interferon (IFN)-gamma for iNOS expression in human DLD-1 colon carcinoma cells. Detection of both IL-22 receptor chains and STAT3 phosphorylation proved robust IL-22 responsiveness of these cells. Short interfering RNA technology identified STAT3 as being crucial for up-regulation of iNOS…
Tristetraprolin regulation of interleukin-22 production
2015
AbstractInterleukin (IL)-22 is a STAT3-activating cytokine displaying characteristic AU-rich elements (ARE) in the 3′-untranslated region (3′-UTR) of its mRNA. This architecture suggests gene regulation by modulation of mRNA stability. Since related cytokines undergo post-transcriptional regulation by ARE-binding tristetraprolin (TTP), the role of this destabilizing protein in IL-22 production was investigated. Herein, we demonstrate that TTP-deficient mice display augmented serum IL-22. Likewise, IL-22 mRNA was enhanced in TTP-deficient splenocytes and isolated primary T cells. A pivotal role for TTP is underscored by an extended IL-22 mRNA half-life detectable in TTP-deficient T cells. Lu…
Leptin and Its Receptor are Overexpressed in Brain Tumors and Correlate with the Degree of Malignancy
2009
Although leptin and its receptor (ObR) have emerged as important cancer biomarkers, the role of the leptin system in brain tumor development remains unknown. We screened 87 human brain tumor biopsies using immunohistochemistry and detected leptin and ObR in 55.2% and 60.9% cases, respectively. In contrast, leptin and ObR were absent in 14 samples of normal brain tissue. The presence of leptin correlated with ObR with overall concordance 80.5%. The leptin/ObR system was highly expressed in glioblastomas and anaplastic astrocytomas, while lower expression of both markers was noted in low-grade astrocytomas and gangliogliomas. The association between leptin/ObR and the degree of tumor malignan…
PARD3 Inactivation in Lung Squamous Cell Carcinomas Impairs STAT3 and Promotes Malignant Invasion.
2015
Abstract Correct apicobasal polarization and intercellular adhesions are essential for the appropriate development of normal epithelia. Here, we investigated the contribution of the cell polarity regulator PARD3 to the development of lung squamous cell carcinomas (LSCC). Tumor-specific PARD3 alterations were found in 8% of LSCCs examined, placing PARD3 among the most common tumor suppressor genes in this malignancy. Most PAR3-mutant proteins exhibited a relative reduction in the ability to mediate formation of tight junctions and actin-based protrusions, bind atypical protein kinase C, activate RAC1, and activate STAT3 at cell confluence. Thus, PARD3 alterations prevented the formation of c…
Novel Signal Transduction Pathways: Analysis of STAT-3 and Rac-1 Signaling in Inflammatory Bowel Disease
2006
Although the precise etiology of inflammatory bowel disease still remains unclear, considerable progress has been made in the identification of novel signal transduction pathways that elucidate the immunopathogenesis involved in the perpetuation of the inflammatory process. Augmented T cell resistance against apoptosis is regarded as a pivotal factor in the pathogenesis, as it impairs mucosal homeostasis and leads to unrestrained accumulation of activated T cells, which subsequently lead to the amplification of the inflammatory response. Therefore novel therapeutic strategies aim at restoring mucosal T cell susceptibility to apoptosis through targeting of signal transduction pathways that a…
Rtp1p Is a Karyopherin-Like Protein Required for RNA Polymerase II Biogenesis
2013
The assembly and nuclear transport of RNA polymerase II (RNA pol II) are processes that require the participation of many auxiliary factors. In a yeast genetic screen, we identified a previously uncharacterized gene, YMR185w (renamed RTP1), which encodes a protein required for the nuclear import of RNA pol II. Using protein affinity purification coupled to mass spectrometry, we identified interactions between Rtp1p and members of the R2TP complex. Rtp1p also interacts, to a different extent, with several RNA pol II subunits. The pattern of interactions is compatible with a role for Rtp1p as an assembly factor that participates in the formation of the Rpb2/Rpb3 subassembly complex and its bi…
The MAPK Hog1 recruits Rpd3 histone deacetylase to activate osmoresponsive genes
2003
Regulation of gene expression by mitogen-activated protein kinases (MAPKs) is essential for proper cell adaptation to extracellular stimuli. Exposure of yeast cells to high osmolarity results in rapid activation of the MAPK Hog1, which coordinates the transcriptional programme required for cell survival on osmostress. The mechanisms by which Hog1 and MAPKs in general regulate gene expression are not completely understood, although Hog1 can modify some transcription factors. Here we propose that Hog1 induces gene expression by a mechanism that involves recruiting a specific histone deacetylase complex to the promoters of genes regulated by osmostress. Cells lacking the Rpd3-Sin3 histone deac…
Response of the Saccharomyces cerevisiae Mpk1 Mitogen-Activated Protein Kinase Pathway to Increases in Internal Turgor Pressure Caused by Loss of Ppz…
2004
ABSTRACT The Mpk1 pathway of Saccharomyces cerevisiae is a key determinant of cell wall integrity. A genetic link between the Mpk1 kinase and the Ppz phosphatases has been reported, but the nature of this connection was unclear. Recently, the Ppz phosphatases were shown to be regulators of K + and pH homeostasis. Here, we demonstrate that Ppz-deficient strains display increased steady-state K + levels and sensitivity to increased KCl concentrations. Given these observations and the fact that K + is the major determinant of intracellular turgor pressure, we reasoned that the connection between PPZ1 and - 2 and MPK1 was due to the combination of increased internal turgor pressure in Ppz-defic…
Expression of a Truncated Yeast Ccc1 Vacuolar Transporter Increases the Accumulation of Endogenous Iron
2021
Iron is an essential micronutrient for all eukaryotic organisms because it participates as a redox cofactor in multiple metabolic processes. Iron bioavailability is highly restricted due to the low solubility of its oxidized form, frequently leading to iron deficiency anemia. The baker’s yeast Saccharomyces cerevisiae is used as a model organism for iron homeostasis studies, but also as a food supplement and fermentative microorganism in the food industry. Yeast cells use the vacuolar Ccc1 transporter to detoxify and store excess iron in the vacuoles. Here, we modulate CCC1 expression and properties to increase iron extraction from the environment. We show that constitutive expression of fu…