Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.7.7.6 (RNA polymerase)
34,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We investigated the expression of several mRNAs in exoerythrocytic and erythrocytic stages of Plasmodium yoelii in infected mice, focusing our attention on genes thought to be involved in signal transduction (like pypka and pymap-1, encoding homologues of cAMP-dependent and mitogen-activated protein kinases, respectively) and cell cycle progression (those encoding the cdc2-related kinases Pycrk-1, Pycrk-3 and Pymrk). Messengers coding for enzymes involved in general processes such as DNA replication and RNA transcription (both subunits of the ribonucleotide reductase (Pyrnr1, Pyrnr2) and RNA polymerase II) as well as a messenger coding for Pys21, a sexual stage-specific protein, were also investigated. Total RNA was prepared from livers of infected mice at different times post sporozoite inoculation. In contrast to the pys21 transcript, which was observed only in infected erythrocytes, all messenger species could be detected in the liver by RT-PCR, peaking at 43 h post infection, a time when parasite burden was maximum, and decreasing markedly thereafter to become hardly visible at 168 h. Some transcripts (pypka, pymap-1, pyrnr1 and pyrnr2) could be detected 12 h after infection, while others (pymrk and pyrnapolII) did not become detectable until 24 h. In addition, we characterised all these messengers by Northern blot of total RNAs extracted from infected erythrocytes. Taken together, these data suggest that a similar set of regulatory genes is expressed during both exoerythrocytic and erythrocytic schizogony.
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PMID:A study of selected Plasmodium yoelii messenger RNAs during hepatocyte infection. 1108 14

The recent advances on the cytoplasmic regulators of the induction of germinal vesicle break down, maturation and degeneration of oocytes, and glycosaminoglycan composition during cumulus expansion of cumulus-oocyte complexes are discussed. A) Inactive mitogen-activated protein kinases (MAPKs) are present in the oocytes at germinal vesicle (GV) stage, and are activated with germinal vesicle breakdown (GVBD), and remain highly active throughout maturation in porcine oocytes. Inactive MAPKs are localized in the cytoplasm of GV-arrested oocytes and active MAPKs were detected in the GV just before GVBD. B) Cumulus expansion of porcine cumulus-oocyte complexes (COCs) was reduced by oocy tectomy. The profile of total glycosaminoglycan synthesis was attributed to hyaluronic acid rather than chondroitin sulfate in intact COCs and oocytectomy reduced hyaluronic acid synthesis. C) The abnormalities of chromosomes and alpha-tubulin morphology were observed in the oocytes of c-mos deficient mice. MAPK activity of c-mos deficient oocytes did not significantly fluctuate throughout maturation and was clearly lower than that of wild-type oocytes. One of the most drastic abnormalities in c-mos knockout mouse oocytes was their entrance into the interphase instead of second meiosis after first polar body emission. D) Reverse transcriptase/polymerase chain reaction-Southern blot hybridization demonstrated positive expression of Fas in intraovarian mouse oocytes. In contrast, expression of Fas ligand was detected in granulosa cells. These findings were histologically confirmed by in situ hybridization with Fas- and FasL-specific probes. Co-culture of intact and zona-free eggs and granulosa cells demonstrated positive TUNEL staining only zona-free eggs.
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PMID:Morphological dynamics of cumulus-oocyte complex during oocyte maturation. 1131 42

The carboxyl-terminal domain (CTD) of the largest subunit of mammalian RNA polymerase II (RNAP II) consists of 52 repeats of a consensus heptapeptide and is subject to phosphorylation and dephosphorylation events during each round of transcription. RNAP II activity is regulated during the cell cycle and cell cycle-dependend changes in RNAP II activity correlate well with CTD phosphorylation. In addition, global changes in the CTD phosphorylation status are observed in response to mitogenic or cytostatic signals such as growth factors, mitogens and DNA-damaging agents. Several CTD kinases are members of the cyclin-dependent kinase (CDK) superfamily and associate with transcription initiation complexes. Other CTD kinases implicated in cell cycle regulation include the mitogen-activated protein kinases ERK-1/2 and the c-Abl tyrosine kinase. These observations suggest that reversible RNAP II CTD phosphorylation may play a key role in linking cell cycle regulatory events to coordinated changes in transcription.
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PMID:Regulation of RNA polymerase II activity by CTD phosphorylation and cell cycle control. 1180 20

The budding yeast Saccharomyces cerevisiae differentiates into filamentous invasively growing forms under conditions of nutrient limitation. This response is dependent on the transcription factor Ste12 and on the mating pheromone-response mitogen-activated protein (MAP) kinase cascade, but a mechanism for regulation of Ste12 by nutrient limitation has not been defined. Here we show that Ste12 function in filamentous growth is regulated by the cyclin-dependent kinase Srb10 (also known as Cdk8), which is associated with the RNA polymerase II holoenzyme. Srb10 inhibits filamentous growth in cells growing in rich medium by phosphorylating Ste12 and decreasing its stability. Under conditions of limiting nitrogen, loss of Srb10 protein and kinase activity occurs, with a corresponding loss of Ste12 phosphorylation. Mutation of the Srb10-dependent phosphorylation sites increases pseudohyphal development but has no effect on the pheromone response of haploid yeast. Srb10 kinase activity is also regulated independently of the mating pheromone-response pathway. This indicates that Srb10 controls Ste12 activity for filamentous growth in response to nitrogen limitation and is consistent with the hypothesis that Srb10 regulates gene-specific activators in response to physiological signals to coordinate gene expression with growth potential.
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PMID:Srb10/Cdk8 regulates yeast filamentous growth by phosphorylating the transcription factor Ste12. 1252 Mar 6

RNA polymerase (pol) III transcription increases within minutes of serum addition to growth-arrested fibroblasts. We show that ERK mitogen-activated protein kinases regulate pol III output by directly binding and phosphorylating the BRF1 subunit of transcription factor TFIIIB. Blocking the ERK signalling cascade inhibits TFIIIB binding to pol III and to transcription factor TFIIIC2. Chromatin immunoprecipitation shows that the association of BRF1 and pol III with tRNA(Leu) genes in cells decreases when ERK is inactivated. Furthermore, mutation of an ERK docking domain or phosphoacceptor site in BRF1 prevents serum induction of pol III transcription. These data identify a novel target for ERK, and suggest that its ability to stimulate biosynthetic capacity and growth involves direct transcriptional activation of tRNA and 5S rRNA genes.
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PMID:The mitogen-activated protein (MAP) kinase ERK induces tRNA synthesis by phosphorylating TFIIIB. 1274 36

Srb11p-Srb10p is the budding yeast C-type cyclin-cyclin-dependent kinase that is required for the repression of several stress response genes. To relieve this repression, Srb11p is destroyed in cells exposed to stressors, including heat shock and oxidative stress. In the present study, we identified Ask10p (for activator of Skn7) by two-hybrid analysis as an interactor with Srb11p. Coimmunoprecipitation studies confirmed this association, and we found that, similar to Srb11p-Srb10p, Ask10p is a component of the RNA polymerase II holoenzyme. Ask10p is required for Srb11p destruction in response to oxidative stress but not heat shock. Moreover, this destruction is important since the hypersensitivity of an ask10 mutant strain to oxidative stress is rescued by deleting SRB11. We further show that Ask10p is phosphorylated in response to oxidative stress but not heat shock. This modification requires the redundant mitogen-activated protein (MAP) kinase kinase Mkk1/2 but not their normal MAP kinase target Slt2p. Moreover, the other vegetative MAP kinases--Hog1p, Fus3p, or Kss1p--are not required for Ask10p phosphorylation, suggesting the existence of an alternative pathway for transducing the Pkc1p-->Bck1-->Mkk1/2 oxidative stress signal. In conclusion, Ask10p is a new component of the RNA polymerase II holoenzyme and an important regulator of the oxidative stress response. In addition, these results define a new role for the Pkc1p MAP kinase cascade (except the MAP kinase itself) in transducing the oxidative damage signal directly to the RNA polymerase II holoenzyme, thereby bypassing the stress-activated transcription factors.
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PMID:Ask10p mediates the oxidative stress-induced destruction of the Saccharomyces cerevisiae C-type cyclin Ume3p/Srb11p. 1455 78

Expression of human beta-defensins is correlated with differentiation in the oral epithelium, consistent with their function as part of the epithelial antimicrobial barrier. Because calcium is a known regulator of epithelial differentiation, we tested the hypothesis that calcium concentration mediates beta-defensin expression. Gingival epithelial cells were cultured in medium containing low calcium concentration (0.03 mM), then either changed to high extracellular calcium concentrations or stimulated with thapsigargin to release intracellular calcium stores in the presence or absence of BAPTA-AM, a calcium chelator. Human beta-defensin-2 (hBD-2) mRNA expression was rapidly induced by thapsigargin, and more slowly induced by high extracellular calcium. Induction of hBD-2 peptide was confirmed by immunofluorescence. BAPTA-AM inhibited hBD-2 induction by both thapsigargin and calcium in a dose-dependent fashion. In addition, BAPTA-AM inhibited hBD-2 induction by a bacterial stimulant. Collectively, these findings demonstrate that intracellular calcium is a critical mediator of hBD-2 expression. Abbreviations used in this study are: BAPTA-AM, 1,2-bis(2-aminophenoxy)-ethane-N,N,N',N'-tetra-acetic acid tetrakis (acetoxymethyl ester); DMSO, dimethylsulfoxide; F. nucleatum, Fusobacterium nucleatum; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; HBDs, human beta-defensins; HGECs, human gingival epithelial cells; MAP, mitogen-activated protein; and RT-PCR, reverse-transcriptase/polymerase chain-reaction.
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PMID:Intracellular calcium in signaling human beta-defensin-2 expression in oral epithelial cells. 1457 98

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 deacetylase complex are sensitive to high osmolarity and show compromised expression of osmostress genes. Hog1 interacts physically with Rpd3 in vivo and in vitro and, on stress, targets the deacetylase to specific osmostress-responsive genes. Binding of the Rpd3-Sin3 complex to specific promoters leads to histone deacetylation, entry of RNA polymerase II and induction of gene expression. Together, our data indicate that targeting of the Rpd3 histone deacetylase to osmoresponsive promoters by the MAPK Hog1 is required to induce gene expression on stress.
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PMID:The MAPK Hog1 recruits Rpd3 histone deacetylase to activate osmoresponsive genes. 1473 71

TATA binding protein (TBP) is a central transcription factor used by all three cellular RNA polymerases. Changes in the levels of TBP have been shown to have selective effects on gene activity. Overexpression of TBP has been recently shown to contribute to cellular transformation, and elevated levels of TBP occur in a clinically significant proportion of human colon tumors relative to matched normal tissue. To understand the mechanisms by which TBP is regulated, we have analyzed whether activation of the epidermal growth factor receptor (EGFR), a membrane-bound tyrosine receptor kinase that is activated in a large number of human cancers, can serve to regulate cellular TBP. We show that treatment of mouse epidermal cells with EGF produces an increase in TBP levels, which can be blocked with an EGFR-specific inhibitor. In contrast, TBP levels remain unchanged after EGF treatment of EGFR null cells. EGF-mediated increases in TBP are regulated at the transcriptional level, as transient expression of the human TBP promoter is induced with EGF. This regulatory event is dependent upon the downstream activation of Ras and requires the activation of p38, JNK, and ERK mitogen-activated protein kinases. The consequence of elevated TBP on gene expression was further determined. Transcription by RNA polymerase (Pol) I and III was induced by EGF. Directly overexpressing TBP also stimulated transcription from these promoters. Thus, we have identified a new and important target of EGFR signaling, TBP, that contributes to EGF-mediated stimulation of RNA Pol I- and III-dependent gene activity. Since the cellular levels of the products of these genes, tRNAs and rRNAs, determine the translational capacity of cells, this event may be an important contributor to the transforming function of EGF.
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PMID:Epidermal growth factor enhances cellular TATA binding protein levels and induces RNA polymerase I- and III-dependent gene activity. 1516 79

The prevalence of esophageal adenocarcinoma in the setting of Barrett's metaplasia continues to increase in Western nations at a rate greater than any other cancer. The trophic properties of gastrin have been documented in gastric, pancreatic and colon cancer cell lines, suggesting a potential role for this regulatory peptide in the growth of these malignancies. The aims of these studies were to identify and characterize the presence of functional cholecystokinin type-2 (gastrin) receptors on the membranes of human esophageal adenocarcinoma cells. Reverse transcriptase-polymerase chain reaction (RT-PCR) demonstrated the presence of cholecystokinin type-2 receptor transcripts in human esophageal adenocarcinoma cell lines. Competitive binding assays revealed specific binding of gastrin in SEG-1 cells (IC50 of 2.4 x 10(-8) M). This finding was confirmed by laser scanning confocal microscopy through internalization of rhodamine green labeled gastrin heptapeptide in SEG-1 cells. Gastrin caused a dose-dependent increase in proliferation of SEG-1 cells when compared to controls. This effect was abolished by co-incubation with L365,260, a CCK-2-specific receptor antagonist. Gastrin-induced phosphorylation of the p44 and p42 mitogen-activated protein kinases was demonstrated by Western blot analysis. In conclusion, the studied human esophageal adenocarcinoma cell lines possess cholecystokinin type-2 (gastrin) receptors. Receptors bind gastrin, resulting in increased proliferation in SEG-1 cells.
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PMID:Gastrin stimulates receptor-mediated proliferation of human esophageal adenocarcinoma cells. 1517 38


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