Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.10.1 (ERK)
 95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Flow to myocardium following coronary occlusion may not originate solely from collateral channels. Some flow might be derived from overlapping coronary arteries which also perfuse tissue within the territory of the obstructed vessel prior to occlusion. Left atrial microsphere injection during perfusion of the left anterior descending (LAD) artery from a special reservoir containing microsphere-free blood and again after LAD occlusion permitted measurement of noncollateral overlap and total ischemic LAD (TIF) flows, respectively, and mathematical derivation of true collateral flow (TCF). Whereas TIF averaged 0.25 +/- 0.03 ml/min per g, TCF was 0.14 +/- 0.03 ml/min per g, only 50.6% of TIF. The remainder of the TIF represented either inadvertant inclusion of normally perfused tissue with the ischemic LAD myocardium or actual overlap of LAD and left circumflex circulations. 86RbCl was injected simultaneously with the microspheres following coronary occlusion. 86Rb and microsphere densities in the whole heart and ischemic area were closely correlated, although microsphere distribution tended to be more heterogeneous. No segment of ischemic myocardium containing 86Rb was free of microspheres. Therefore, the geometry of undeveloped collateral channels is adequate to permit passage of 15-micron particles. Absolute 86Rb flows were consistently less than microsphere flows.
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PMID:Quantitation of collateral and ischemic flows with microspheres and diffusible indicator. 64 87

14-C-nicotine was incubated with 10000 X g supernatant fraction of liver homogenate from female mice (C3H/TIF/BOM) 2, 12 and 18 months old. The rate of metabolism was measured by the determination of the oxidative nicotine metabolite continine and by determining the disappearance of nicotine. No significant changes between different ages were found either in the continine formation or the rate of disappearance of nicotine.
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PMID:In vitro metabolism of nicotine in liver of ageing mice. 87 9

VP16 (also called Vmw65 and alpha TIF) is a structural protein of herpes simplex virus type 1 (HSV-1) that trans-induces HSV-1 immediate-early gene transcription. This report describes an HSV-1 VP16 deletion mutant that was constructed and propagated in a cell line transformed with a VP16 expression vector. The VP16 deletion mutant replicated like wild-type HSV-1 during infection of the VP16-expressing cell line. Deletion mutant virions propagated in this cell line contained wild-type, cell-derived VP16 protein that was recruited during virion assembly and was functional for immediate-early gene trans-induction. The mutant failed to replicate during subsequent infection of cells that do not express VP16, as determined in plaque assays and single-step replication assays. The deletion mutant induced nearly normal levels of viral DNA synthesis and capsid production during these infections, but it induced slightly lower levels of viral DNA encapsidation and appeared by transmission electron microscopy to be defective in further steps of virion maturation. A genetic revertant of the deletion mutant that was restored for VP16-coding sequences exhibited fully wild-type replication properties in both VP16-expressing and nonexpressing cells. The absence of VP16 protein synthesis at late times of HSV-1 infection prevents the production of infectious progeny virus and correlates with a profound defect in HSV-1 particle assembly.
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PMID:Deletion of the VP16 open reading frame of herpes simplex virus type 1. 130 45

A virion protein of herpes simplex virus type-1, called Vmw65, alpha TIF or VP16, interacts with cellular transcription factors to transactivate immediate early viral genes. We have cloned and determined the nucleotide sequence of the gene encoding the homologous protein in bovine herpesvirus 1 (BHV-1). The amino acid sequence of the BHV-1 protein is similar to that of alpha TIF, except in the C-terminal one-third of the protein. Since the ability of alpha TIF to activate transcription is dependent on this region, our results suggest that the BHV-1 homologue either does not act as a transactivator or activates genes by a different mechanism.
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PMID:Sequences of the bovine herpesvirus 1 homologue of herpes simplex virus type-1 alpha-trans-inducing factor (UL48). 132 63

Varicella-Zoster virus (VZV) is a neurotropic alphaherpes virus closely related to herpes simplex virus (HSV). However, unlike its close relative HSV, VZV lacks a functional alpha-TIF (alpha-gene transinducing factor) that activates the transcription of immediate early genes during the initial events of the virus life cycle. Hence, in the absence of a functional alpha-TIF, the mechanism triggering the expression of immediate early genes in VZV at present remains unclear. Accumulating evidence indicates that the gene product of the putative immediate early gene ORF62 (IE62) plays a pivotal role in activating VZV genes of all three putative kinetic classes, namely immediate early (alpha), early (beta), and late (gamma) classes of VZV genes. In the present study, we show that IE62 can positively autoregulate its cognate promoter using a transient transfection assay, both in lymphocytes and in neural cells. In the same system, we can also demonstrate activation of the VZV IE62 promoter by HSV ICP4. By deletion analysis and oligonucleotide-directed site-specific mutagenesis we have localized specific regions in the IE62 promoter/upstream sequences that mediate inducibility by IE62 and HSV ICP4, and provide evidence that this promoter activation by these two proteins may be through different mechanisms. These data, taken together with the recent demonstration of the presence of IE62 in the VZ virion tegument (Kinchington, P.R., Hoagland, J.K., Arvin, A.M., Ruyechan, W.T., and Hay, J. 1992. J. Virol. 66, 359-366) provides a possible mechanism by which the triggering of VZV gene expression occurs in the absence of a functional alpha-TIF protein.
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PMID:The varicella-zoster virus immediate early protein, IE62, can positively regulate its cognate promoter. 132 24

Homeo domain proteins exhibit distinct biological functions with specificities that cannot be predicted by their sequence specificities for binding DNA. Recognition of the surface of the Oct-1 POU homeo domain provides a general model for the contribution of selective protein-protein interactions to the functional specificity of the homeo domain family of factors. The assembly of Oct-1 into a multiprotein complex on the herpes simplex virus alpha/IE enhancer is specified by the interactions of its homeo domain with ancillary factors. This complex (C1 complex) is composed of the viral alpha TIF protein (VP16), Oct-1, and one additional cellular component, the C1 factor. Variants of the Oct-1 POU homeo domain were generated by site-directed mutagenesis, which altered the residues predicted to form the exposed surface of the domain-DNA complex. Proteins with single amino acid substitutions on the surface of either helix 1 or 2 of the Oct-1 POU homeo domain had decreased abilities to form the C1 complex. The behavior of these mutants in a cooperative DNA-binding assay with alpha TIF suggested that the Oct-1 POU homeo domain is principally recognized by alpha TIF in the C1 complex. The preferential recognition of Oct-1 over the closely related Oct-2 protein is critically influenced by a single residue on the surface of helix 1 because the introduction of this residue into the Oct-2 POU homeo domain significantly enhanced its ability to form a C1 complex.
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PMID:Recognition of the surface of a homeo domain protein. 135 55

In a reconstituted system consisting of partially purified RNA polymerase I (pol I) and the initiation factors TIF-IA, TIF-IB, and TIF-IC, the nucleolar factor UBF (upstream binding factor) stimulates transcription from the rRNA-encoding DNA (rDNA) promoter at least 50-fold. This activation is not observed at high template concentrations or in the presence of highly purified pol I. Template commitment experiments suggest that UBF activates transcription by relieving inhibition exerted by a negative-acting factor(s) in the polymerase fraction that competes for TIF-IB binding to the rDNA promoter and prevents the formation of preinitiation complexes. Using purified histone H1 bound to DNA as a model for the repressed state of the rDNA promoter, we show that UBF counteracts H1-mediated repression of pol I transcription. The implications of these findings are discussed with respect to the protein-protein and protein-DNA interactions at the rDNA promoter and the possible involvement of UBF in control of ribosomal gene transcription.
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PMID:Dual role of the nucleolar transcription factor UBF: trans-activator and antirepressor. 150 43

The components required for specific transcription of ribosomal RNA were isolated from logarithmically growing Acanthamoeba castellanii. The transcription initiation factor fraction, TIF, and RNA polymerase I were extracted from whole cells at 0.35 M KCl. The extract was fractionated with polyethylenimine, then chromatographed on phosphocellulose (P11) which resulted in the separation of TIF from RNA polymerase I. The fractions containing TIF were further chromatographed on DEAE cellulose (DE52), Heparin Affigel, and Matrex green agarose, followed by sedimentation through glycerol gradients. TIF was purified approximately 17,000-fold, and shown to have a native molecular weight of 289 kD, and to bind specifically to rRNA promoter sequences by DNase I footprinting. The addition of homogeneous RNA polymerase I to this complex permitted the initiation of specific transcription in vitro. The phosphocellulose fractions containing RNA polymerase I were chromatographed on DEAE cellulose, Heparin-Sepharose, DEAE-Sephadex, and sedimented through sucrose gradients. Polymerase I was purified to apparent homogeneity with a yield of 8.1% and a specific activity of 315. It contained one fewer subunit than previously reported. DNase I protection experiments demonstrated that in both partially purified and homogeneous fractions, RNA polymerase I was capable of stable binding to the TIF-rDNA complex, and correctly initiating transcription on rDNA templates.
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PMID:Purification of components required for accurate transcription of ribosomal RNA from Acanthamoeba castellanii. 162 Jun 19

In herpes simplex virus 1, the five alpha genes are induced by alpha-transinducing factor (alpha TIF; VP16), a virion protein, acting in concert with Oct-1 and other cellular proteins on a cis-acting site in the promoter domain of alpha genes. Because alpha TIF is an essential virion protein, its function as an inducer can best be evaluated only by mutating the cis-acting site. Earlier we reported on a series of 17 mutations in and around the cis-acting site of a 275-bp alpha 27 promoter fused to a reporter gene and recombined into the viral genome. These recombinant viruses were tested in Vero cells in the presence of cycloheximide, and we demonstrated that mutations in the sequence required for Oct-1 binding abolished transactivation whereas mutations in the alpha TIF-dependent GARAT sequence decreased but did not abolish transactivation. We now report that (i) in limited-passage human embryonic lung cells, alpha gene expression from promoters mutated in the GARAT sequences is often higher and more variable than in Vero cells, (ii) in the absence of cycloheximide, the mutant viruses show less significant impairment of reporter gene expression, (iii) Oct-1 can bind either to the overlapping octamer element or to various TAATGARAT sequences with differing degrees of binding strength and these relative binding levels correlate well with levels of gene expression observed in infected cells, (iv) in the cis-acting site upstream of the alpha 4 gene, no degenerate overlapping Oct-1 sequence exists, and therefore in this instance Oct-1 must be binding directly to the TAATGARAT sequence, (v) extension of the alpha 27 promoter by an additional 1,334 bp results in much higher expression of the reporter gene as a result of additional upstream cis-acting sites, and (vi) obliteration of the most proximal Oct-1 binding element within the 275-bp promoter dramatically reduces gene expression even in the presence of the additional upstream cis-acting sites.
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PMID:Role of alpha-transinducing factor (VP16) in the induction of alpha genes within the context of viral genomes. 164 82

We have used purified transcription factors and RNA polymerase I (pol I) to analyze the individual steps involved in the formation of transcription initiation complexes at the mouse ribosomal gene promoter in vitro. Complete assembly of transcription complexes requires pol I and at least four auxiliary factors, termed TIF-IA, TIF-IB, TIF-IC, and UBF. Preincubation and template commitment, as well as order of addition protocols, were used to discriminate between various intermediate complexes generated during assembly of the initiation complex. As a first step, TIF-IB binds to the core promoter, a process that is facilitated by the upstream control element and the upstream binding factor (UBF). Binding of TIF-IB to the rDNA promoter results in the formation of a functional preinitiation complex (complex 1), which is stable for many rounds of transcription. UBF, which on its own does not stably associate with the rDNA promoter, triggers a 5-10-fold increase in the overall amount of this primary complex. Following binding of TIF-IB and UBF to the template DNA, pol I and TIF-IC successively bind, yielding complexes 2 and 3, respectively. Transcription-competent initiation complexes are built up by the final association of the growth-regulated factor TIF-IA. The various complexes can be distinguished by their different sensitivity to Sarkosyl. Only the complete complex consisting of all four factors and pol I shows resistance to intermediate concentrations of Sarkosyl (0.045%) and is competent to catalyze the formation of the first phosphodiester bond. The initiated complex is, on the other hand, resistant to high concentrations of Sarkosyl (0.3%). The hierarchical nature of the different complexes formed suggests a model for transcription initiation and predicts functions for the individual factors.
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PMID:Transcription complex formation at the mouse rDNA promoter involves the stepwise association of four transcription factors and RNA polymerase I. 176 56


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