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

---

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

Human intercellular adhesion molecule-1 (ICAM-1), a specific ligand for the lymphocyte function-associated Ag-1 (LFA-1), plays an important role in leukocyte-endothelial cell interactions. It is induced by proinflammatory cytokines such as IL-1, TNF-alpha, or IFN-gamma. However, little is known concerning the intracellular regulatory mechanisms which trigger ICAM-1 up-regulation. In order to study potential regulatory elements involved in ICAM-1 induction we have cloned the human ICAM-1 gene and 5 kb of its 5'-regulatory region. The sequence of the cDNA was found to be distributed over seven exons separated by six introns, whereby each of the five extracellular Ig-like domains of ICAM-1 is encoded by its own exon. The upstream sequence harbors a number of sequence motifs implicated in the regulation and expression of eukaryotic genes, including binding sites for the transcription factors SP-1, AP-1, and NF-kB. Primer extension and S1 nuclease analysis revealed two transcription initiation sites 319 bp and 41 bp upstream of the translation start site. Consensus TATA boxes were found at the expected positions about 25 bp upstream of both start sites. Reverse transcriptase polymerase chain reaction showed differential use of the two TATA boxes in A549 and HS913T cells. Both RNA seem to code for the same for of ICAM-1 protein. For regulation studies a 1.3-kb EcoRI/SalI fragment of the 5'-flanking region was used to promote transcription of a linked luciferase reporter gene in transient-transfection assays in A549 and HS913T cells. Treatment of A549 cells with IL-1 or TNF-alpha resulted in a two- or fourfold increase in luciferase activity. Furthermore, a sixfold induction could be achieved after treatment with the phorbol ester PMA. In contrast, agents that increase intracellular cAMP levels did not induce luciferase activity. Northern blot analysis was used to investigate the kinetics of ICAM-1 mRNA synthesis upon induction with TNF-alpha and PMA. These data suggest that the up-regulation of ICAM-1 by cytokines occurs at least partly at the transcriptional level. Deletion analysis of the 1.3-kb fragment of the 5'-flanking region revealed sequences responsible for promotion and inhibition of transcription. In particular, two functionally distinct regions have been characterized: a short fragment containing an NF-kB binding site has been shown to function as an activator, followed immediately downstream by a sequence acting as a silencer element. Therefore, ICAM-1 gene expression seems to be modulated by multiple cis-acting elements.
...
PMID:Cloning of the human gene for intercellular adhesion molecule 1 and analysis of its 5'-regulatory region. Induction by cytokines and phorbol ester. 168 Sep 19

Host cell RNA synthesis is inhibited by poliovirus infection. We have studied the mechanism of poliovirus-induced inhibition of RNA polymerase II-mediated transcription by using the adenovirus early region 3 (E3) promoter. In vitro transcription from the E3 promoter was severely inhibited in extracts prepared from poliovirus-infected HeLa cells. Four regions in the E3 promoter have been shown to serve as binding sites for cellular transcription factors. These regions contain binding sites for transcription factors NF-1 (site IV), AP-1 (site III), CREB/ATF (site II), and the TATA factor (site I). Binding to these four regions was not significantly altered by poliovirus infection as assayed by DNase I footprinting analysis; furthermore, gel retardation assays failed to reveal dramatic differences in the total amount of CREB/ATF-, AP-1-, and NF-1-binding activity present in mock- or poliovirus-infected cell extracts. Gel retardation assays, however, did reveal significant qualitative differences in the DNA-protein complexes formed with a CREB/ATF-binding site in extracts prepared from poliovirus-infected cells as compared to mock-infected cell extracts. Radioimmunoprecipitation reactions performed with antiserum against CREB/ATF revealed a severe reduction in a phosphorylated form of the protein present in poliovirus-infected cell extracts. However, in vitro kinase reactions demonstrated that mock- and poliovirus-infected cell extracts contained similar levels of CREB/ATF. Expression from the E3 promoter was shown to be activated by CREB/ATF in vivo; this induction was dependent upon the phosphorylation of CREB/ATF. Thus, we propose that poliovirus infection inhibits transcription from the E3 promoter, at least in part, through the dephosphorylation of CREB/ATF.
...
PMID:Loss of a phosphorylated form of transcription factor CREB/ATF in poliovirus-infected cells. 216 27

Expression of ornithine decarboxylase is regulated by a variety of hormonal and other stimuli in rat cells and tissues. To study this phenomenon at the molecular level, we isolated and sequenced a cDNA-encoding rat ornithine decarboxylase and deduced its amino acid sequence. The cDNA clone was used to isolate a clone from a rat genomic library which contained the sequence of the entire rat ornithine decarboxylase gene. The gene comprised 12 exons and 11 introns and spanned 7.7 kilobases. Two polyadenylation signals (AATAAA) were located 310 and 697 base pairs 3' to the translational termination codon and were responsible for the occurrence of two hybridizing mRNA species in Northern blots of rat cells and tissues. S1 nuclease mapping suggested that there were multiple transcriptional start sites; the major one appeared to be located 2269 base pairs of genomic sequence 5' to the ATG translational initiation site, representing 274 bases of mRNA. Several potential regulatory elements were identified in the 5'-promoter regions or in the first intron: a TATA box, GC boxes, AP-1 and AP-2 binding sites, a cAMP-responsive element, a glucocorticoid regulatory element, and RNA polymerase III promoter sequences. The 5'-noncoding region of the mRNA was extremely rich in G + C; secondary structure predictions suggested that almost this entire region could form stable secondary structures, with an overall free energy of formation (delta G) of -114 kcal/mol. The potential regulatory elements identified in both the promoter region of the gene and the 5'-untranslated region of the mRNA may be involved in the complex regulation of rat ornithine decarboxylase expression.
...
PMID:Rat ornithine decarboxylase gene. Nucleotide sequence, potential regulatory elements, and comparison to the mouse gene. 272 15

Transcriptional activation of RNA polymerase II in eukaryotic organisms ranging from yeasts to mammals has many common features such as enhancer elements, TATA elements, and activator proteins that bind specifically to promoter DNA. The JUN oncoprotein, which causes sarcomas in chickens, shows significant homology to the DNA-binding domain of GCN4, a yeast protein that stimulates transcription of the amino acid biosynthetic genes. The GCN4 and JUN proteins bind the same DNA sequences, consensus ATGA(C/G)TCAT, even though the DNA-binding domains are only 45% identical in amino acid sequence. The JUN protein almost certainly represents the oncogenic version of the normal AP-1 transcription factor, suggesting an evolutionary relationship between yeast and vertebrate activator proteins. Here, I demonstrate that JUN efficiently activates transcription in yeast either through its own or a heterologous DNA-binding domain. As is the case for yeast activator proteins, transcriptional stimulation by JUN requires an acidic activation region distinct from the DNA-binding domain. The functional interchangeability between yeast and vertebrate transcription factors strongly suggests a basic similarity in the molecular mechanism of eukaryotic transcriptional activation.
...
PMID:The JUN oncoprotein, a vertebrate transcription factor, activates transcription in yeast. 312 39

Simian virus 40 (SV40) small t antigen (t) can activate transcription from certain RNA polymerase II and III promoters (M. Loeken, I. Bikel, D. M. Livingston, and J. Brady, Cell 55:1171-1177, 1988). Here we report a new function of t, its ability to repress human c-fos promoter and AP-1 transcriptional activity in CV-1P cells. This function is the product of a discrete N-terminal domain of t, because the large T antigen (T)/t-common polypeptide, which contains only the first 82 amino acids common to both T and t of SV40, was, like the intact protein, an active repressor. The data further suggest that the t- and T/t-common-mediated repression of c-fos expression was most likely manifest at the level of transcription. In keeping with the possibility that t affects the expression of the genomic c-fos promoter, it also led to repression of AP-1 formation. Thus, SV40 is both an activator and a repressor of transcription. Its ability to inhibit c-fos expression should be considered in light of the natural history of SV40 in its natural host.
...
PMID:Transrepression of RNA polymerase II promoters by the simian virus 40 small t antigen. 808 58

The regulation of RNA polymerase II-mediated transcription involves both direct and indirect interactions among regulatory proteins and the general transcription factors (GTFs) that assemble at TATA-containing promoters. Here we show that the oncogenic transcription factors Fos and Jun make direct physical contacts with three proteins of the basal transcription apparatus, TFIIE-34 (TFIIE-beta), TFIIF-30 (RAP30), and TFIIF-74 (RAP74). The interactions among the activator proteins and these three GTFs were not detected with other transcription factors, including some bZIP protein family members. Both coimmunoprecipitation and protein blotting experiments demonstrated that the interactions were strongly favored by dimerization of Fos and Jun and that they involved the basic region and basic region-proximal domain of both proteins. Mutations within the DNA-binding domains of Fos and Jun abolished binding to GTFs, although the presence of DNA was not required for the association. Surprisingly, only a single basic region in the context of a protein dimer was sufficient for the interaction. Squelching of AP-1-dependent transcription in vitro by an excess of Fos-Jun dimers was relieved by the addition of TFIIE, indicating that it is a direct functional target of Fos and Jun. These results suggest that dimerization induces a conformational alteration in the basic region of Fos and Jun that promotes an association with TFIIE-34 and TFIIF, thus contributing to transcription initiation.
...
PMID:Fos-Jun dimerization promotes interaction of the basic region with TFIIE-34 and TFIIF. 862 77

We have used the human lung surfactant protein B (SP-B) gene as a template for in vitro transcription studies. Transcription factors were provided by nuclear extracts from a cultured line of human lung (type II-like) cells. Elements upstream of -50 had essentially no effect on the efficiency of the SP-B promoter in vitro. However, a deletion of the region from +8 to +8 reduced in vitro transcription by a factor of 10. The only factor whose binding was detected between +1 and +100 by footprinting, and between +12 and +38 by electrophoretic mobility shift analysis (EMSA), was a member of the AP-1 family. Mutation of 4 of 7 bases of the AP-1 site reduced transcription two-fold and ablated the AP-1 EMSA binding complex observed on the SP-B downstream region (+12 to +38). Competition with unlabeled AP-1 consensus oligonucleotide abolished the downstream footprint over the AP-1 site. Thus, the SP-B promoter is one of a very small class of RNA polymerase II promoters that are strongly dependent in vitro on sequence elements downstream of the transcription start site, and, in this case, the AP-1 consensus element and surrounding sequences.
...
PMID:A downstream AP-1 element regulates in vitro lung transcription from the human pulmonary surfactant protein B promoter. 875 33

All the angiotensin peptides originate from angiotensinogen, a glycoprotein synthesized by several tissues, including the brain and the anterior pituitary. In the rat, immunohistochemistry has been used to localize angiotensinogen in gonadotropes and in uncharacterized cells surrounding sinusoids. Both cell types are capable of secreting angiotensinogen in cell culture; only the gonadotropes contain angiotensin II (AngII) and are capable of secreting it in culture. It has been asserted that the perisinusoidal cells are the only source of angiotensinogen for the generation of AngII by gonadotropes. Our current data favor the existence of a complete intracellular renin-angiotensin system (RAS) in gonadotropes and a separate extracellular system which utilizes the high concentration of angiotensinogen from perisinusoidal cells. Furthermore, we postulate that gonadotrope AngII serves mainly reproductive functions, while the proximity of angiotensinogen-secreting cells to folliculostellate cells, and their access to the intercellular sinusoidal and follicular spaces, places the extracellular RAS in a strategic position to affect pituitary growth and the mediation of acute-phase immune responses. In the rat brain, angiotensinogen is expressed by the 16-18th day of fetal life and by areas generally concerned with vasopressor, electrolyte, and fluid homeostasis. Antisense deoxyoligonucleotides to angiotensinogen mRNA lower blood pressure in hypertensive rats and inhibit in vitro growth of neuroblastoma cells, indicating a significant role for angiotensinogen in mitogenic and homeostatic functions. It is commonly agreed that astrocytes express angiotensinogen. Neuronal angiotensinogen has also been demonstrated by immunohistochemistry, as a secretion from neuronal cell cultures, and by reverse-transcriptase polymerase chain reaction. The fate of secreted astrocytic and neuronal angiotensinogen remains obscure. Angiotensinogen is regulated in a tissue-specific manner with smaller or absent responses observed for brain tissue. By using astrocyte and neuronal cultures the actions on angiotensinogen production of growth hormone, IGF-1, inflammatory lipopolysaccharide, and phorbol ester have been examined. Recent observations show that angiotensinogen is regulated positively or negatively by glucocorticoids and that a positive synergism between cAMP and glucocorticoids exists. On the basis of analogous systems for other proteins, a scheme involving glucocorticoid receptors, CREB, and AP-1 transcription factors is formulated to explain glucocorticoid-cAMP interactions. These transcriptional interactions may form a significant functional link between the RAS and adrenergic mechanisms.
...
PMID:Novel perspectives on pituitary and brain angiotensinogen. 910 Dec 59

The human gene for the seventh largest subunit of RNA polymerase II complex, hsRPB7 was cloned, sequenced and mapped. This complex is an integral part of the transcription-coupled DNA repair mechanism and has been shown to be involved in several human genetic diseases and implicated in many others. The hsRPB7 gene consists of 8 exons and spans approximately 5.1 kb. Southern blots of genomic and cloned DNA suggest that hsRPB7 is coded for by a single gene. Using human radiation hybrids and YACs, the gene was localized to 11q13.1, within 70 kb of marker D11S1765. The sequence of the 5' flanking region does not contain a TATA element, but does contain several Sp1 binding sites, an AP-1 site and a novel inverted polymorphic GATA tandem repeat. This novel GATA repeat can be used for linkage analysis. The hsRPB7 gene seems to be highly conserved among eukaryotic species, showing general sequence conservation to yeast and Drosophila. Northern blot analysis reveals a high degree of tissue-specific expression. For example, adult retina, brain and kidney exhibit a relatively high level of expression. A moderate level of expression is observed in heart, lung, testis, cornea, retinal pigmented epithelium/choroid and placenta with a lower level of expression in the uterus, small intestine and skeletal muscle. A very low level of expression was observed in stomach and liver. Comparison between four fetal and adult tissues also demonstrate a surprising level of developmental specificity. Expression in fetal retina is considerably lower than fetal brain but similar to adult retina.
...
PMID:Human gene for the RNA polymerase II seventh subunit (hsRPB7): structure, expression and chromosomal localization. 925 63

GnRH receptors belong to the family of G protein-coupled receptor proteins and have been localized to the anterior pituitary, brain and reproductive organs as well as many steroid-dependent tumor tissues. Recently, cDNAs for the GnRH receptors of several species including the human have been cloned. To determine the structure of the gene encoding the human GnRH receptor, we isolated the receptor gene clones from the human genomic libraries. Comparison of the genomic and cDNA sequences revealed that the human GnRH receptor gene is composed of three exons and two introns and spans over 20 kb in size. Exon 1 encodes the 5' untranslated sequence and nucleotide +1 to +522 in the open reading frame, exon 2 encodes nucleotide +523 to +742 and exon 3 encodes nucleotide +743 to +987 in the open reading frame as well as the 3' untranslated sequence. Southern blot analysis of genomic DNA and localization of the GnRH receptor gene to a single site on human chromosome 4 (4q13) indicate the presence of a single copy of the gene in the human genome. Several regulatory sequences for various hormones and other regulatory factors were identified, including PEA-3, AP-1, AP-2, and Pit-1 sites. In addition, glucocorticoid/progesterone response element thyroid hormone response element, and cAMP response element sequences were identified. Reverse transcriptase-primer extension and 5' RACE analysis of the human pituitary RNA demonstrated the presence of multiple transcriptional start sites upstream of the translational start site. Analysis of the 5' flanking region of the gene also revealed the presence of multiple TATA and CAAT sequences. The finding of multiple transcriptional start sites raises the possibility of tissue-specific regulation and the existence of variable size transcripts. Chimeras containing 1.26 kb (-534 to 728) of the 5' flanking region of the receptor gene and the luciferase (Luc) gene expressed a significant luciferase activity when transfected into a human endometrial tumor cell line (HEC-1A) and a breast tumor cell line (MCF-7) but not in a mouse pituitary gonadotrope cell line (alpha T3-1), suggesting the existence of multiple promoter elements in the gene. These findings indicate a multiplicity of regulation of expression of the GnRH receptor and provide the substrate for detailed investigation in the reproductive system.
...
PMID:Molecular structure of the human gonadotropin-releasing hormone receptor gene. 1102 3


1 2 3 4 5 6 Next >>

---