Search results for "Pathway"
showing 10 items of 1685 documents
Inappropriate translation inhibition and P-body formation cause cold-sensitivity in tryptophan-auxotroph yeast mutants
2017
In response to different adverse conditions, most eukaryotic organisms, including Saccharomyces cerevisiae, downregulate protein synthesis through the phosphorylation of eIF2α (eukaryotic initiation factor 2α) by Gcn2, a highly conserved protein kinase. Gcn2 also controls the translation of Gcn4, a transcription factor involved in the induction of amino acid biosynthesis enzymes. Here, we have studied the functional role of Gcn2 and Gcn2-regulating proteins, in controlling translation during temperature downshifts of TRP1 and trp1 yeast cells. Our results suggest that neither cold-instigated amino acid limitation nor Gcn2 are involved in the translation suppression at low temperature. Howev…
Programming of Intestinal Epithelial Differentiation by IL-33 Derived from Pericryptal Fibroblasts in Response to Systemic Infection.
2016
SummaryThe intestinal epithelium constitutes an efficient barrier against the microbial flora. Here, we demonstrate an unexpected function of IL-33 as a regulator of epithelial barrier functions. Mice lacking IL-33 showed decreased Paneth cell numbers and lethal systemic infection in response to Salmonella typhimurium. IL-33 was produced upon microbial challenge by a distinct population of pericryptal fibroblasts neighboring the intestinal stem cell niche. IL-33 programmed the differentiation of epithelial progenitors toward secretory IEC including Paneth and goblet cells. Finally, IL-33 suppressed Notch signaling in epithelial cells and induced expression of transcription factors governing…
Affinity proteomics identifies novel functional modules related to adhesion GPCRs.
2019
Adhesion G protein-coupled receptors (ADGRs) have recently become a target of intense research. Their unique protein structure, which consists of a G protein-coupled receptor combined with long adhesive extracellular domains, suggests a dual role in cell signaling and adhesion. Despite considerable progress in the understanding of ADGR signaling over the past years, the knowledge about ADGR protein networks is still limited. For most receptors, only a few interaction partners are known thus far. We aimed to identify novel ADGR-interacting partners to shed light on cellular protein networks that rely on ADGR function. For this, we applied affinity proteomics, utilizing tandem affinity purifi…
Induction of dormancy in hypoxic human papillomavirus-positive cancer cells
2017
Oncogenic human papillomaviruses (HPVs) are closely linked to major human malignancies, including cervical and head and neck cancers. It is widely assumed that HPV-positive cancer cells are under selection pressure to continuously express the viral E6/E7 oncogenes, that their intracellular p53 levels are reconstituted on E6/E7 repression, and that E6/E7 inhibition phenotypically results in cellular senescence. Here we show that hypoxic conditions, as are often found in subregions of cervical and head and neck cancers, enable HPV-positive cancer cells to escape from these regulatory principles: E6/E7 is efficiently repressed, yet, p53 levels do not increase. Moreover, E6/E7 repression under …
Oxidative stress, autophagy, epigenetic changes and regulation by miRNAs as potential therapeutic targets in osteoarthritis
2015
Aging is a natural process characterized by the declining ability of the different organs and tissues to respond to stress, increasing homeostatic imbalance and risk of disease. Osteoarthritis (OA) is a multifactorial disease in which cartilage degradation is a central feature. Aging is the main risk factor for OA. In OA cartilage, a decrease in the number of chondrocytes and in their ability to regenerate the extracellular matrix and adequately respond to stress has been described. OA chondrocytes show a senescence secretory phenotype (SSP) consisting on the overproduction of cytokines (interleukins 1 and 6), growth factors (e.g., epidermal growth factor) and matrix metalloproteinases (MMP…
Therapeutic potential of polyphenols in cardiovascular diseases: Regulation of mTOR signaling pathway
2020
Cardiovascular diseases comprise of non-communicable disorders that involve the heart and/or blood vessels and have become the leading cause of death worldwide with increased prevalence by age. mTOR is a serine/threonine-specific protein kinase which plays a central role in many physiological processes including cardiovascular diseases, and also integrates various proliferative signals, nutrient and energy abundance and stressful situations. mTOR also acts as central regulator during chronic stress, mitochondrial dysfunction and deregulated autophagy which are associated with senescence. Under oxidative stress, mTOR has been reported to exert protective effects regulating apoptosis and auto…
The claustrum is a target for projections from the supramammillary nucleus in the rat.
2019
Injection of the anterograde tracer Phaseolus vulgaris leucoagglutinin (PHAL) into the rat rostral and caudal supramammillary nucleus (SUM) provided expected patterns of projections into the hippocampus and the septal region. In addition, unexpectedly intense projections were observed into the claustrum defined by parvalbumin expression. Injections of the retrograde tracer fluorogold (FG) into the hippocampus and the region of the claustrum showed that the cells of origin of these projections distributed similarly within the borders of the SUM. The SUM is usually involved in control of hippocampal theta activity, but the observation of intense projections into the claustrum indicates that i…
Snapshots of a shrinking partner: Genome reduction inSerratia symbiotica
2016
AbstractGenome reduction is pervasive among maternally-inherited endosymbiotic organisms, from bacteriocyte- to gut-associated ones. This genome erosion is a step-wise process in which once free-living organisms evolve to become obligate associates, thereby losing non-essential or redundant genes/functions. Serratia symbiotica (Gammaproteobacteria), a secondary endosymbiont present in many aphids (Hemiptera: Aphididae), displays various characteristics that make it a good model organism for studying genome reduction. While some strains are of facultative nature, others have established co-obligate associations with their respective aphid host and its primary endosymbiont (Buchnera). Further…
Molecular profiling of pancreatic neuroendocrine tumors (pNETS) and the clinical potential
2018
Abstract: Introduction: Pancreatic neuroendocrine tumors (pNETs) represent a small part of pancreatic neoplasms, and the knowledge about their indolent clinical course remains a subject of investigation. They occur sporadically or as part of familial cancer syndromes and are classified by WHO in 3 categories. There is ongoing research to understand their molecular profiling and leading mutations.Areas covered: The aim of this review is to clarify the overall aspects of tumorigenesis, to expose the latest developments in understanding the course of the disease and the possible therapeutic implications of these. The review also discusses functional and non-functional pNETs and associated inhe…
GSK-3 in liver diseases: Friend or foe?
2020
Liver diseases, including hepatitis due to hepatitis B or C virus infection, non-alcoholic fatty liver disease, and hepatocellular carcinoma pose major challenges for overall health due to limited curative treatment options. Thus, there is an urgent need to develop new therapeutic strategies for the treatment of these diseases. A better understanding of the signaling pathways involved in the pathogenesis of liver diseases can help to improve the efficacy of emerging therapies, mainly based on pharmacological approaches, which influence one or more specific molecules involved in key signal transduction pathways. These emerging therapies are very promising for the prevention and treatment of …