Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.7.6 (RNA polymerase)
 34,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In liver mitochondria from alloxan diabetic rats the biosynthesis of RNA (as measured by 14C-orotic acid incorporation and RNA polymerase activity) and protein (as measured by 14C-leucine incorporation) were decreased. In contrast, insulin (20 U kg-1) injected to intact or diabetic rats increased both these measures. However, no change of mitochondrial DNA biosynthesis (as measured by incorporation of 3H-thymidine) was found. It was concluded that in liver cells insulin plays an important role in regulation of biosynthesis not only of nuclear (cytoplasmic) but also of mitochondrial RNA and proteins.
 ...
PMID:Effect of insulin on RNA and protein biosynthesis in liver mitochondria from normal and alloxan diabetic rats. 31 94

Insulin-like growth factors I and II (IGF I and II) are polypeptides with both growth-promoting and insulin-like metabolic effects. Immunoreactive IGF I is present in the retina and both IGF I and II are present in vitreal fluid. The type I and type II IGF receptors are also localized within the neural retina. The presence of IGFs and IGF receptors within the eye suggests a possible growth-promoting effect of IGFs on ocular tissues. IGF may enter the eye from the blood or, alternatively, arise from an ocular cell type which synthesizes and secretes IGF. IGF I and II mRNA synthesis in scleral cells and IGF I synthesis in rat retina suggests endogenous IGF production in the eye. We hypothesized that IGFs and IGF receptors are synthesized by one ocular cell type, the retinal pigment-epithelium (RPE). As a first step in studying IGF production by the RPE, we analyzed expression of the IGF and IGF receptor genes by cultured human RPE cells. Using Northern analysis, RNase protection and reverse-transcriptase polymerase chain reaction (RT-PCR), we found that cultured RPE cells synthesize mRNA for IGF I and the type I and type II IGF receptors.
 ...
PMID:Gene expression of the insulin-like growth factors and their receptors in cultured human retinal pigment epithelial cells. 137 66

The influence of Insulin-like Growth Factor I (IGF-I) on some metabolic functions of Sertoli cells from peripubertal rats was investigated. Sertoli cells were isolated from the testes of 24-day-old animals and cultured at 32 degrees C in Eagle's MEM with or without 1 nM IGF-I. Sertoli cells cultured in the presence of IGF-I showed increased nuclear RNA polymerase activity (+80%) and augmented protein synthesis (+50%).
 ...
PMID:[Effect of insulin-like growth factor I (IGF-I) on Sertoli cell metabolism in the pubescent rat]. 151 Aug 32

The term vitamin D includes various chemical species. Vitamin D3 a true endogenous or alimentary prohormone is converted into its main metabolite, calcitriol, by successive hydroxylations in the liver in position 25 and in the kidney in position 1, the production of which is controlled by several factors including parathyroid hormone, blood calcium and phosphorus or insulin as well as by the metabolites of the hormone itself. It controls the synthesis of numerous peptides by acting on gene expression. Indeed, several structural proteins are involved including procollagen alpha 1l, core protein of proteoglycans, diverse regulatory peptides such as protooncogene c-myc and growth factors, "Tumor Necrosis Factor or TNF" and "Nerve Growth Factor or NGF" or hormones such as parathyroid hormone, and finally constitutive proteins of the mineralized tissues such as osteonectin, osteocalcin, osteopontin and calbindins. Therefore, it modulates very different cellular processes. It acts via a nuclear receptor the structure and function of which have been investigated by genetic engineering (cloning of genes encoding for the receptor and hormono-dependent peptides, transfection assays, directed mutagenesis). Actual studies investigate its role in the formation of the complex for transcription initiation near ADN sites, the "Vitamin D Responsive Element or VDRE", located upstream vitamin D-responsive genes and approximately RNA polymerase II. The receptor, which is present in many cell types at various concentrations, would determine spatial and temporal patterns of calcitriol action during development in conjunction with chromatin factors.
 ...
PMID:[Vitamin D: biosynthesis, metabolism and mechanism of action at the cellular level]. 164 84

Effects of dexamethasone, EGF and insulin on the synthesis of rRNA and phosphorylation of nucleolin in primary cultures of adult rat hepatocytes were studied. Hepatocytes were incubated for 8 h with EGF (20 ng/ml) plus insulin (0.1 microM) and/or for 20 h with dexamethasone (1 microM) before the end of incubation. The incorporation of [3H]uridine into acid-insoluble materials and the nuclear activity of RNA polymerase I were stimulated approx. 2-fold with EGF plus insulin and these were further enhanced 2-3-times by dexamethasone, although dexamethasone alone exerted no stimulation. When hepatocytes were incubated with [32P]orthophosphate, similar enhancement by these hormones was also observed in the phosphorylation of a nucleolar protein, nucleolin, which was detected by immunoprecipitation with anti-nucleolin antibodies. The amount of nucleolin was slightly increased by EGF plus insulin in the presence of dexamethasone, but scarcely changed by treatment with EGF plus insulin or dexamethasone alone. Cycloheximide inhibited RNA synthesis to a greater or lesser degree in the case of all hepatocytes which were cultured with or without these hormonal treatments. These results indicate that the in vivo effect of glucocorticoid on rRNA synthesis and nucleolin phosphorylation in liver is primarily a direct action on parenchymal cells and requires other growth factors such as EGF and insulin.
 ...
PMID:Synergistic stimulatory effect of glucocorticoid, EGF and insulin on the synthesis of ribosomal RNA and phosphorylation of nucleolin in primary cultured rat hepatocytes. 171 Sep 32

Rat liver protein disulfide isomerase (PDI) catalyzes the oxidative folding of proteins containing disulfide bonds. We have developed an efficient method for its overproduction in Escherichia coli. Using a T7 RNA polymerase expression system, isolated yields of 15-30 mg/liter of recombinant rat PDI are readily obtained. Convenient purification of the enzyme from E. coli lysates involves ion-exchange (DEAE) chromatography combined with zinc chelate chromatography. The recombinant PDI shows catalytic activity identical to that of PDI isolated from bovine liver in both the reduction of insulin and the oxidative folding of ribonuclease A. The enzyme is expressed in E. coli as a soluble, cytoplasmic protein. After complete reduction and denaturation in 6 M guanidinium hydrochloride, PDI regains complete activity within 3 min after removal of the denaturant, implying that disulfide bonds are not essential for the maintenance of PDI tertiary structure. Both the protein isolated from E. coli and the protein isolated from liver contained free cysteine residues (1.8 +/- 0.2 and 1.4 +/- 0.3 SH/monomer, respectively).
 ...
PMID:Expression and purification of recombinant rat protein disulfide isomerase from Escherichia coli. 182 89

The gene encoding rat fructose-1,6-bisphosphatase was isolated from a rat genomic Charon 4A library by screening with a cDNA to the rat liver enzyme. Southern blotting of rat genomic DNA showed that there is a single copy of the fructose-1,6-bisphosphatase gene. It extends over 23 kilobases and is composed of seven exons and six introns that range in size from 93 to 267 base pairs and from 1,400 to 11,300 base pairs, respectively. The intron/exon boundary sequences conform to consensus acceptor (GTn) and donor (nAG) sequences, and the exons in the gene appear to code for functional protein domains. The transcription start site, determined by 5'-extension sequencing of mRNA, was assigned to a guanine 119 bases 5' to the translation initiation AUG. The sequence of the gene upstream to the cap site contains characteristic RNA polymerase II promoter-binding sites: a putative TATA box at position -29 and a Sp 1 binding site (GGGGCGGAGA) at position -48. A 1,300-base pair fragment of 5'-flanking sequence containing these elements, ligated upstream from a firefly luciferase reporter gene and transfected into cultured normal rat kidney cells, demonstrated strong promoter activity. The accumulation of fructose-1,6-bisphosphatase mRNA in hepatocytes incubated with cAMP suggests that the gene may be cAMP-responsive, which is consistent with the presence of three consensus cAMP regulatory elements at positions -169, -282, and -698 in the 5'-flanking region of the gene. Expression of the fructose-1,6-bisphosphatase promoter-driven luciferaes gene was 2-3-fold activated by the cyclic nucleotide, suggesting that one or more of these elements may be functional. On the other hand, insulin decreased the expression of the endogenous gene in hepatocytes. Thus, expression of the fructose-1,6-bisphosphatase gene is regulated independently by both cAMP and insulin.
 ...
PMID:The rat fructose-1,6-bisphosphatase gene. Structure and regulation of expression. 184 13

Synthetic peptides have been used to define the consensus amino acid sequence for substrate recognition by the meiosis-activated myelin basic protein (MBP) kinase (p44mpk), which was purified from maturing sea star oocytes. This protein kinase shares many properties with the mitogen-activated microtubule-associated protein-2 kinase (p42mapk) in vertebrates. Recently, Thr-97 in the tryptic fragment KNIVTPRTPPPSQGK of bovine MBP was identified as the major site of phosphorylation by p44mpk (Sanghera, J. S., Aebersold, R., Morrison, H. D., Bures, E. J., and Pelech, S. L. (1990) FEBS Lett. 273, 223-226). Synthetic peptides modeled after this sequence revealed that the presence of a proline residue C-terminal (+1 position) to the phosphorylatable threonine (or serine) residue was critical for recognition by p44mpk. Although not essential, a proline residue located at the -2 position enhanced the Vmax of peptide phosphorylation. Basic, acidic, and non-polar residues were equally tolerated at the -1 position. The presence of an amino acid residue at position -3 also increased peptide phosphorylation. Thus, the optimum consensus sequence for phosphorylation by p44mpk was defined as Pro-X-(Ser/Thr)-Pro, where X is a variable amino acid residue, but ideally not a Pro. Peptides that included this sequence were phosphorylated by p44mpk with Vmax values approaching 1 mumol.min-1.mg-1 and with apparent Km values of approximately 1 mM). Pseudosubstrate peptides in which the phosphorylatable residue was replaced by valine or alanine were weak inhibitors of p44mpk (apparent Ki values of approximately 3 mM). Over 40 distinct protein kinases contain Pro-X-(Ser/Thr)-Pro sequences including the human receptors for insulin and epidermal growth factor, and kinases encoded by the human proto-oncogenes abl, neu, and raf-1, and Schizosaccharomyces pombe cell cycle control genes ran-1 and wee-1. Multiple putative sites were also identified in rat microtubule-associated protein-2, human retinoblastoma protein, human tau protein, and Drosophila myb protein and RNA polymerase II.
 ...
PMID:Definition of a consensus sequence for peptide substrate recognition by p44mpk, the meiosis-activated myelin basic protein kinase. 190 71

The expression of genes that code for the large ribosomal RNAs (rRNAs) and tRNAs can be regulated by calcium, serum, insulin and a tumor-promoting phorbol ester, TPA. These effectors can rapidly alter rRNA and tRNA synthesis in dividing and nondividing Drosophila cells. In an in vitro assay system of the nondividing cells of the male accessory glands, calcium, insulin and TPA were shown to increase both rRNA and tRNA synthesis. Exposure of actively dividing Drosophila culture cells to differing serum concentrations or TPA also altered rRNA and tRNA synthesis. Nuclear run-on assays demonstrate that the exposure of these cells to increased serum concentrations coordinately alters RNA polymerase I loading on both 18S and 28S rDNA. These data indicate that calcium, growth factors and a tumor-promoter each can signal changes in ribosomal and tRNA gene expression.
 ...
PMID:Serum, insulin and phorbol esters stimulate rRNA and tRNA gene expression in both dividing and nondividing Drosophila cells. 192 1

We have studied the effect of triiodothyronine (T3) on RNA synthesis by primary cultures of rat hepatocytes in order to ascertain whether hepatocyte transcriptional activity is directly stimulated by this hormone. The results demonstrate that T3 stimulates RNA synthesis as measured by [3H]orotic acid incorporation into RNA and by RNA polymerase activity. The responsiveness of cultured hepatocytes to T3 becomes evident only after a fairly long latency period required for the recovery of T3 nuclear binding sites. The response of RNA synthesis to T3 was absent unless the hepatocytes were simultaneously exposed to insulin and dexamethasone, indicating a permissive role of these factors in the action of T3 on RNA synthesis.
 ...
PMID:Triiodothyronine-stimulated RNA synthesis in primary cultures of adult rat hepatocytes. 241 99


1 2 3 4 5 6 7 8 9 10 Next >>