Search results for "factor"
showing 10 items of 17757 documents
The ribosome assembly gene network is controlled by the feedback regulation of transcription elongation
2017
Ribosome assembly requires the concerted expression of hundreds of genes, which are transcribed by all three nuclear RNA polymerases. Transcription elongation involves dynamic interactions between RNA polymerases and chromatin. We performed a synthetic lethal screening in Saccharomyces cerevisiae with a conditional allele of SPT6, which encodes one of the factors that facilitates this process. Some of these synthetic mutants corresponded to factors that facilitate pre-rRNA processing and ribosome biogenesis. We found that the in vivo depletion of one of these factors, Arb1, activated transcription elongation in the set of genes involved directly in ribosome assembly. Under these depletion c…
Enterococcus hirae and Barnesiella intestinihominis Facilitate Cyclophosphamide-Induced Therapeutic Immunomodulatory Effects.
2016
International audience; The efficacy of the anti-cancer immunomodulatory agent cyclophosphamide (CTX) relies on intestinal bacteria. How and which relevant bacterial species are involved in tumor immunosurveillance, and their mechanism of action are unclear. Here, we identified two bacterial species, Enterococcus hirae and Barnesiella intestinihominis that are involved during CTX therapy. Whereas E. hirae translocated from the small intestine to secondary lymphoid organs and increased the intratumoral CD8/ Treg ratio, B. intestinihominis accumulated in the colon and promoted the infiltration of IFN-gamma-producing gamma delta Tau cells in cancer lesions. The immune sensor, NOD2, limited CTX…
Molecular evolution of antioxidant and hypoxia response in long-lived, cancer-resistant blind mole rats: The Nrf2-Keap1 pathway.
2015
The Nrf2-Keap1 pathway is crucial for the cellular antioxidant and hypoxia response in vertebrates. Deciphering its modifications in hypoxia-adapted animals will help understand its functionality under environmental stress and possibly allow for knowledge transfer into biomedical research. The blind mole rat Spalax, a long-lived cancer-resistant rodent, lives in burrows underground and is adapted to severely hypoxic conditions. Here we have conducted a bioinformatical survey of Spalax core genes from the Nrf2-Keap1 pathway on the coding sequence level in comparison to other hypoxia-tolerant and -sensitive rodents. We find strong sequence conservation across all genes, illustrating the pathw…
Brain size and limits to adult neurogenesis
2015
The walls of the cerebral ventricles in the developing embryo harbor the primary neural stem cells from which most neurons and glia derive. In many vertebrates, neurogenesis continues postnatally and into adulthood in this region. Adult neurogenesis at the ventricle has been most extensively studied in organisms with small brains, such as reptiles, birds, and rodents. In reptiles and birds, these progenitor cells give rise to young neurons that migrate into many regions of the forebrain. Neurogenesis in adult rodents is also relatively widespread along the lateral ventricles, but migration is largely restricted to the rostral migratory stream into the olfactory bulb. Recent work indicates t…
Sox8 and Sox10 jointly maintain myelin gene expression in oligodendrocytes
2017
In Schwann cells of the vertebrate peripheral nervous system, induction of myelination and myelin maintenance both depend on the HMG-domain-containing transcription factor Sox10. In oligodendrocytes of the central nervous system, Sox10 is also essential for the induction of myelination. Its role in late phases of myelination and myelin maintenance has not been studied so far. Here, we show that these processes are largely unaffected in mice that lack Sox10 in mature oligodendrocytes. As Sox10 is co-expressed with the related Sox8, we also analyzed oligodendrocytes and myelination in Sox8-deficient mice. Again, we could not detect any major abnormalities. Expression of many myelin genes was …
The Absence of HIF-1α Increases Susceptibility to Leishmania donovani Infection via Activation of BNIP3/mTOR/SREBP-1c Axis
2020
Summary: Hypoxia-inducible factor-1 alpha (HIF-1α) is considered a global regulator of cellular metabolism and innate immune cell functions. Intracellular pathogens such as Leishmania have been reported to manipulate host cell metabolism. Herein, we demonstrate that myeloid cells from myeloid-restricted HIF-1α-deficient mice and individuals with loss-of-function HIF1A gene polymorphisms are more susceptible to L. donovani infection through increased lipogenesis. Absence of HIF-1α leads to a defect in BNIP3 expression, resulting in the activation of mTOR and nuclear translocation of SREBP-1c. We observed the induction of lipogenic gene transcripts, such as FASN, and lipid accumulation in inf…
Inhibition of STAT3 with the generation 2.5 antisense oligonucleotide, AZD9150, decreases neuroblastoma tumorigenicity and increases chemosensitivity
2017
Abstract Purpose: Neuroblastoma is a pediatric tumor of peripheral sympathoadrenal neuroblasts. The long-term event-free survival of children with high-risk neuroblastoma is still poor despite the improvements with current multimodality treatment protocols. Activated JAK/STAT3 pathway plays an important role in many human cancers, suggesting that targeting STAT3 is a promising strategy for treating high-risk neuroblastoma. Experimental Design: To evaluate the biologic consequences of specific targeting of STAT3 in neuroblastoma, we assessed the effect of tetracycline (Tet)-inducible STAT3 shRNA and the generation 2.5 antisense oligonucleotide AZD9150 which targets STAT3 in three representat…
Nutritional control of IL-23/Th17-mediated autoimmune disease through HO-1/STAT3 activation
2017
AbstractThe nutritional curcumin (CUR) is beneficial in cell-mediated autoimmune diseases. The molecular mechanisms underlying this food-mediated silencing of inflammatory immune responses are poorly understood. By investigating antigen-specific immune responses we found that dietary CUR impairs the differentiation of Th1/Th17 cells in vivo during encephalomyelitis and instead promoted Th2 cells. In contrast, feeding CUR had no inhibitory effect on ovalbumin-induced airway inflammation. Mechanistically, we found that CUR induces an anti-inflammatory phenotype in dendritic cells (DC) with enhanced STAT3 phosphorylation and suppressed expression of Il12b and Il23a. On the molecular level CUR …
Hot1 factor recruits co-activator Sub1 and elongation complex Spt4/5 to osmostress genes.
2016
Hyperosmotic stress response involves the adaptative mechanisms needed for cell survival. Under high osmolarity conditions, many stress response genes are activated by several unrelated transcription factors that are controlled by the Hog1 kinase. Osmostress transcription factor Hot1 regulates the expression of several genes involved in glycerol biosynthesis, and the presence of this transcription factor in their promoters is essential for RNApol II recruitment. The physical association between Hog1 and Hot1 activates this transcription factor and directs the RNA polymerase II localization at these promoters. We, herein, demonstrate that physical and genetic interactions exist between Hot1 …
Regulation of yeast fatty acid desaturase in response to iron deficiency
2017
Unsaturated fatty acids (UFA) are essential components of phospholipids that greatly contribute to the biophysical properties of cellular membranes. Biosynthesis of UFAs relies on a conserved family of iron-dependent fatty acid desaturases, whose representative in the model yeast Saccharomyces cerevisiae is Ole1. OLE1 expression is tightly regulated to adapt UFA biosynthesis and lipid bilayer properties to changes in temperature, and in UFA or oxygen availability. Despite iron deficiency being the most extended nutritional disorder worldwide, very little is known about the mechanisms and the biological relevance of fatty acid desaturases regulation in response to iron starvation. In this re…