Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Mammalian mediator of transcriptional regulation and its possible role as an end-point of signal transduction pathways.

ABSTRACT: A multiprotein complex isolated from murine cells is identified as a counterpart of the yeast Mediator of transcriptional regulation on the basis of the following: homologs of two subunits of yeast Mediator, Srb7 and Med7, copurify with the complex; peptide sequencing reveals, in addition, homologs of the yeast Mediator subunits Rgr1 and Med6; as with yeast Mediator, the mouse complex binds to the RNA polymerase II C-terminal domain (CTD) and stimulates phosphorylation of the CTD by TFIIH. Peptide sequencing also identifies a component of mouse Mediator as a relative of Ring-3 protein, a mitogen-activated nuclear protein kinase, raising the possibility of Mediator as an end point of signal transduction pathways.

SUBMITTER: Jiang YW

PROVIDER: S-EPMC21111 | biostudies-literature | 1998 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Mammalian mediator of transcriptional regulation and its possible role as an end-point of signal transduction pathways.

Jiang Y W YW Veschambre P P Erdjument-Bromage H H Tempst P P Conaway J W JW Conaway R C RC Kornberg R D RD

Proceedings of the National Academy of Sciences of the United States of America 19980701 15

A multiprotein complex isolated from murine cells is identified as a counterpart of the yeast Mediator of transcriptional regulation on the basis of the following: homologs of two subunits of yeast Mediator, Srb7 and Med7, copurify with the complex; peptide sequencing reveals, in addition, homologs of the yeast Mediator subunits Rgr1 and Med6; as with yeast Mediator, the mouse complex binds to the RNA polymerase II C-terminal domain (CTD) and stimulates phosphorylation of the CTD by TFIIH. Pepti ...[more]

PMID: 9671713

Similar Datasets

Context-dependent transcriptional regulations between signal transduction pathways.

Project description:BackgroundCells coordinate their metabolism, proliferation, and cellular communication according to environmental cues through signal transduction. Because signal transduction has a primary role in cellular processes, many experimental techniques and approaches have emerged to discover the molecular components and dynamics that are dependent on cellular contexts. However, omics approaches based on genome-wide expression analysis data comparing one differing condition (e.g. complex disease patients and normal subjects) did not investigate the dynamics and inter-pathway cross-communication that are dependent on cellular contexts. Therefore, we introduce a new computational omics approach for discovering signal transduction pathways regulated by transcription and transcriptional regulations between pathways in signaling networks that are dependent on cellular contexts, especially focusing on a transcription-mediated mechanism of inter-pathway cross-communication.ResultsApplied to dendritic cells treated with lipopolysaccharide, our analysis well depicted how dendritic cells respond to the treatment through transcriptional regulations between signal transduction pathways in dendritic cell maturation and T cell activation.ConclusionsOur new approach helps to understand the underlying biological phenomenon of expression data (e.g. complex diseases such as cancer) by providing a graphical network which shows transcriptional regulations between signal transduction pathways. The software programs are available upon request.

| S-EPMC3225034 | biostudies-literature

PRDM Proteins: Molecular Mechanisms in Signal Transduction and Transcriptional Regulation.

Project description:PRDM (PRDI-BF1 and RIZ homology domain containing) protein family members are characterized by the presence of a PR domain and a variable number of Zn-finger repeats. Experimental evidence has shown that the PRDM proteins play an important role in gene expression regulation, modifying the chromatin structure either directly, through the intrinsic methyltransferase activity, or indirectly through the recruitment of chromatin remodeling complexes. PRDM proteins have a dual action: they mediate the effect induced by different cell signals like steroid hormones and control the expression of growth factors. PRDM proteins therefore have a pivotal role in the transduction of signals that control cell proliferation and differentiation and consequently neoplastic transformation. In this review, we describe pathways in which PRDM proteins are involved and the molecular mechanism of their transcriptional regulation.

| S-EPMC4009873 | biostudies-literature

Innate immune signal transduction pathways to fungal infection: Components and regulation.

Project description:Candida species are significant causes of mucosal and systemic infections in immune compromised populations, including HIV-infected individuals and cancer patients. Drug resistance and toxicity have limited the use of anti-fungal drugs. A good comprehension of the nature of the immune responses to the pathogenic fungi will aid in the developing of new approaches to the treatment of fungal diseases. In recent years, extensive research has been done to understand the host defending systems to fungal infections. In this review, we described how pattern recognition receptors senses the cognate fungal ligands and the cellular and molecular mechanisms of anti-fungal innate immune responses. Furthermore, particular focus is placed on how anti-fungal signal transduction cascades are being activated for host defense and being modulated to better treat the infections in terms of immunotherapy. Understanding the role that these pathways have in mediating host anti-fungal immunity will be crucial for future therapeutic development.

| S-EPMC10924179 | biostudies-literature

BowTieBuilder: modeling signal transduction pathways.

Project description:BackgroundSensory proteins react to changing environmental conditions by transducing signals into the cell. These signals are integrated into core proteins that activate downstream target proteins such as transcription factors (TFs). This structure is referred to as a bow tie, and allows cells to respond appropriately to complex environmental conditions. Understanding this cellular processing of information, from sensory proteins (e.g., cell-surface proteins) to target proteins (e.g., TFs) is important, yet for many processes the signaling pathways remain unknown.ResultsHere, we present BowTieBuilder for inferring signal transduction pathways from multiple source and target proteins. Given protein-protein interaction (PPI) data signaling pathways are assembled without knowledge of the intermediate signaling proteins while maximizing the overall probability of the pathway. To assess the inference quality, BowTieBuilder and three alternative heuristics are applied to several pathways, and the resulting pathways are compared to reference pathways taken from KEGG. In addition, BowTieBuilder is used to infer a signaling pathway of the innate immune response in humans and a signaling pathway that potentially regulates an underlying gene regulatory network.ConclusionWe show that BowTieBuilder, given multiple source and/or target proteins, infers pathways with satisfactory recall and precision rates and detects the core proteins of each pathway.

| S-EPMC2712453 | biostudies-literature

Phosphoregulated orthogonal signal transduction in mammalian cells.

Project description:Orthogonal tools for controlling protein function by post-translational modifications open up new possibilities for protein circuit engineering in synthetic biology. Phosphoregulation is a key mechanism of signal processing in all kingdoms of life, but tools to control the involved processes are very limited. Here, we repurpose components of bacterial two-component systems (TCSs) for chemically induced phosphotransfer in mammalian cells. TCSs are the most abundant multi-component signal-processing units in bacteria, but are not found in the animal kingdom. The presented phosphoregulated orthogonal signal transduction (POST) system uses induced nanobody dimerization to regulate the trans-autophosphorylation activity of engineered histidine kinases. Engineered response regulators use the phosphohistidine residue as a substrate to autophosphorylate an aspartate residue, inducing their own homodimerization. We verify this approach by demonstrating control of gene expression with engineered, dimerization-dependent transcription factors and propose a phosphoregulated relay system of protein dimerization as a basic building block for next-generation protein circuits.

| S-EPMC7303213 | biostudies-literature

Virus interactions with human signal transduction pathways.

Project description:Viruses depend on their hosts at every stage of their life cycles and must therefore communicate with them via Protein-Protein Interactions (PPIs). To investigate the mechanisms of communication by different viruses, we overlay reported pairwise human-virus PPIs on human signalling pathways. Of 671 pathways obtained from NCI and Reactome databases, 355 are potentially targeted by at least one virus. The majority of pathways are linked to more than one virus. We find evidence supporting the hypothesis that viruses often interact with different proteins depending on the targeted pathway. Pathway analysis indicates overrepresentation of some pathways targeted by viruses. The merged network of the most statistically significant pathways shows several centrally located proteins, which are also hub proteins. Generally, hub proteins are targeted more frequently by viruses. Numerous proteins in virus-targeted pathways are known drug targets, suggesting that these might be exploited as potential new approaches to treatments against multiple viruses.

| S-EPMC3407688 | biostudies-literature

Transcriptional profiles of drought-responsive genes in modulating transcription signal transduction, and biochemical pathways in tomato.

Project description:To unravel the molecular mechanisms of drought responses in tomato, gene expression profiles of two drought-tolerant lines identified from a population of Solanum pennellii introgression lines, and the recurrent parent S. lycopersicum cv. M82, a drought-sensitive cultivar, were investigated under drought stress using tomato microarrays. Around 400 genes identified were responsive to drought stress only in the drought-tolerant lines. These changes in genes expression are most likely caused by the two inserted chromosome segments of S. pennellii, which possibly contain drought-tolerance quantitative trait loci (QTLs). Among these genes are a number of transcription factors and signalling proteins which could be global regulators involved in the tomato responses to drought stress. Genes involved in organism growth and development processes were also specifically regulated by drought stress, including those controlling cell wall structure, wax biosynthesis, and plant height. Moreover, key enzymes in the pathways of gluconeogenesis (fructose-bisphosphate aldolase), purine and pyrimidine nucleotide biosynthesis (adenylate kinase), tryptophan degradation (aldehyde oxidase), starch degradation (beta-amylase), methionine biosynthesis (cystathionine beta-lyase), and the removal of superoxide radicals (catalase) were also specifically affected by drought stress. These results indicated that tomato plants could adapt to water-deficit conditions through decreasing energy dissipation, increasing ATP energy provision, and reducing oxidative damage. The drought-responsive genes identified in this study could provide further information for understanding the mechanisms of drought tolerance in tomato.

| S-EPMC2921197 | biostudies-literature

Integration of transcriptional and posttranslational regulation in a glucose signal transduction pathway in Saccharomyces cerevisiae.

Project description:Expression of the HXT genes encoding glucose transporters in the budding yeast Saccharomyces cerevisiae is regulated by two interconnected glucose-signaling pathways: the Snf3/Rgt2-Rgt1 glucose induction pathway and the Snf1-Mig1 glucose repression pathway. The Snf3 and Rgt2 glucose sensors in the membrane generate a signal in the presence of glucose that inhibits the functions of Std1 and Mth1, paralogous proteins that regulate the function of the Rgt1 transcription factor, which binds to the HXT promoters. It is well established that glucose induces degradation of Mth1, but the fate of its paralogue Std1 has been less clear. We present evidence that glucose-induced degradation of Std1 via the SCF(Grr1) ubiquitin-protein ligase and the 26S proteasome is obscured by feedback regulation of STD1 expression. Disappearance of Std1 in response to glucose is accelerated when glucose induction of STD1 expression due to feedback regulation by Rgt1 is prevented. The consequence of relieving feedback regulation of STD1 expression is that reestablishment of repression of HXT1 expression upon removal of glucose is delayed. In contrast, degradation of Mth1 is reinforced by glucose repression of MTH1 expression: disappearance of Mth1 is slowed when glucose repression of MTH1 expression is prevented, and this results in a delay in induction of HXT3 expression in response to glucose. Thus, the cellular levels of Std1 and Mth1, and, as a consequence, the kinetics of induction and repression of HXT gene expression, are closely regulated by interwoven transcriptional and posttranslational controls mediated by two different glucose-sensing pathways.

| S-EPMC1360249 | biostudies-literature

Enzyme localization can drastically affect signal amplification in signal transduction pathways.

Project description:Push-pull networks are ubiquitous in signal transduction pathways in both prokaryotic and eukaryotic cells. They allow cells to strongly amplify signals via the mechanism of zero-order ultrasensitivity. In a push-pull network, two antagonistic enzymes control the activity of a protein by covalent modification. These enzymes are often uniformly distributed in the cytoplasm. They can, however, also be colocalized in space; for instance, near the pole of the cell. Moreover, it is increasingly recognized that these enzymes can also be spatially separated, leading to gradients of the active form of the messenger protein. Here, we investigate the consequences of the spatial distributions of the enzymes for the amplification properties of push-pull networks. Our calculations reveal that enzyme localization by itself can have a dramatic effect on the gain. The gain is maximized when the two enzymes are either uniformly distributed or colocalized in one region in the cell. Depending on the diffusion constants, however, the sharpness of the response can be strongly reduced when the enzymes are spatially separated. We discuss how our predictions could be tested experimentally.

| S-EPMC2014792 | biostudies-literature

Activation of signal transduction pathways during hepatic oncogenesis.

Project description:Understanding the molecular pathogenesis of hepatocellular carcinoma (HCC) is essential to identify therapeutic targets. A hepatitis B virus (HBV) related double transgenic murine model was developed.Liver specific expression of HBV X protein (HBx) and insulin receptor substrate 1 (IRS1) was achieved and transgenic mice were followed from birth to age 21 months. Liver and tumor tissue were assessed for histologic changes as well as activation of signal transduction pathways by qRT-PCR and multiplex ELISA protein assays.Overexpression of HBx and IRS1 stimulates liver cell proliferation in the double transgenic mice. Only the male mice developed HCC starting at age 15-18 months. The IN/IGF1/IRS1/MAPK/ERK and IN/IGF1/IRS1/PI3K/AKT/GSK3? cascades were activated early (6-9 months) in the liver followed by WNT/?-catenin and Notch signaling. Aspartate ?-hydroxylase (ASPH) was found to link these upstream growth factor signaling pathways to downstream Notch activation in tumor tissues.Sustained overexpression of HBx and IRS1 led to constitutive activation of a tripartite growth factor signal transduction cascade in the liver and was necessary and sufficient to promote HCC development and progression.

| S-EPMC4684747 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data