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)

Control of mouse ribosomal RNA synthesis in response to extracellular signals is mediated by TIF-IA, a regulatory factor whose amount or activity correlates with cell proliferation. Factor TIF-IA interacts with RNA polymerase I (pol I), thus converting it into a transcriptionally active holoenzyme, which is able to initiate specifically at the rDNA promoter in the presence of the other auxiliary transcription initiation factors, designated TIF-IB, TIF-IC and UBF. With regard to several criteria, the growth-dependent factor TIF-IA behaves like a bacterial sigma factor: (i) it associates physically with pol I, (ii) it is required for initiation of transcription, (iii) it is present in limiting amounts and (iv) under certain salt conditions, it is chromatographically separable from the polymerase. In addition, evidence is presented that dephosphorylation of pol I abolishes in vitro transcription initiation from the ribosomal gene promoter without significantly affecting the polymerizing activity of the enzyme at nonspecific templates. The involvement of both a regulatory factor and post-translational modification of the transcribing enzyme provides an efficient and versatile mechanism of rDNA transcription regulation which enables the cell to adapt ribosome synthesis rapidly to a variety of extracellular signals.
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PMID:A growth-dependent transcription initiation factor (TIF-IA) interacting with RNA polymerase I regulates mouse ribosomal RNA synthesis. 239 Sep 74

Several viral trans-activators and a tumor promoter were examined for the ability to activate human papillomavirus type 18 (HPV-18) gene expression. A plasmid containing the HPV-18 noncoding region placed upstream of the chloramphenicol acetyltransferase reporter gene was cotransfected with different herpes simplex virus type 1 (HSV-1) genes into several cell lines. Both HSV-1 TIF and ICP0 activated HPV-18 expression; however, activation by TIF was observed only in epithelial cells, while ICP0 stimulated expression in a wide variety of cells. The element activated by both TIF and ICP0 was mapped to a 229-base-pair fragment which also contains an HPV-18 epithelial cell-preferred enhancer. The inclusion of a papillomavirus E2 trans-activator with TIF and ICP0 further increased HPV-18 expression. In contrast, the HSV-1 ICP4 and ICP27 genes, as well as the human T-cell lymphotropic virus type I and human immunodeficiency virus type 1 tat genes, were found to have no effect on HPV-18 expression. In transient assays, the addition of the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) also activated HPV-18 expression. The region of HPV-18 activated by TPA was localized to a sequence which is homologous to other TPA-responsive elements.
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PMID:Activation of human papillomavirus type 18 gene expression by herpes simplex virus type 1 viral transactivators and a phorbol ester. 253 91

The herpes simplex virus transactivator, alpha TIF, stimulates transcription of the alpha/immediate early genes via a cis-acting site containing an octamer element and a conserved flanking sequence. The alpha TIF protein, produced in a baculovirus expression system, nucleates the formation of at least two DNA--protein complexes on this regulatory element. Both of these complexes contain the ubiquitous Oct-1 protein, whose POU domain alone is sufficient to allow assembly of the alpha TIF-dependent complexes. A second member of the POU domain family, the lymphoid specific Oct-2 protein, can also be assembled into similar complexes at high concentrations of alpha TIF protein. These complexes contain at least two cellular proteins in addition to Oct-1. One of these proteins is present in both insect and HeLa cells and probably recognizes sequences in the cis element. The second cellular protein, only present in HeLa cells, probably binds by protein-protein interactions.
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PMID:The octamer-binding proteins form multi-protein--DNA complexes with the HSV alpha TIF regulatory protein. 255 66

Following infection of cells by herpes simplex virus, the cell nucleus is subverted for transcription and replication of the viral genome and assembly of progeny nucleocapsids. The transition from host to viral transcription involves viral proteins that influence the ability of the cellular RNA polymerase II to transcribe a series of viral genes. The regulation of RNA polymerase II activity by viral gene products seems to occur by several different mechanisms: (1) viral proteins complex with cellular proteins and alter their transcription-promoting activity (e.g., alpha TIF), (2) viral proteins bind to specific DNA sequences and alter transcription (e.g., ICP4), and (3) viral proteins affect the posttranslational modification of viral or cellular transcriptional regulatory proteins (e.g., possibly ICP27). Thus, HSV may utilize several different approaches to influence the ability of host-cell RNA polymerase II to transcribe viral genes. Although it is known that viral transcription uses the host-cell polymerase II, it is not known whether viral infection causes a change in the structural elements of the nucleus that promote transcription. In contrast, HSV encodes a new DNA polymerase and accessory proteins that complex with and reorganize cellular proteins to form new structures where viral DNA replication takes place. HSV may encode a large number of DNA replication proteins, including a new polymerase, because it replicates in resting cells where these cellular gene products would never be expressed. However, it imitates the host cell in that it localizes viral DNA replication proteins to discrete compartments of the nucleus where viral DNA synthesis takes place. Furthermore, there is evidence that at least one specific viral gene protein can play a role in organizing the assembly of the DNA replication structures. Further work in this system may determine whether assembly of these structures is essential for efficient viral DNA replication and if so, why assembly of these structures is necessary. Thus, the study of the localization and assembly of HSV DNA replication proteins provides a system to examine the mechanisms involved in morphogenesis of the cell nucleus. Therefore, several critical principles are apparent from these discussions of the metabolism of HSV transcription and DNA replication. First, there are many ways in which the activity of RNA polymerase II can be regulated, and HSV proteins exploit several of these in controlling the transcription of a single DNA molecule. Second, the interplay of these multiple regulatory pathways is likely to control the progress of the lytic cycle and may play a role in determining the lytic versus latent infection decision.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The role of viral and cellular nuclear proteins in herpes simplex virus replication. 255 60

Mouse, rat and human protein factors recognizing regulatory elements of nontranscribed spacer of rat ribosomal genes were studied by gel retardation assay. Protein factors bind specifically to the DNA fragments containing the core promoter sequence of RNA-polymerase I, to "spacer" promoter and to a putative enhancer sequence. Factors of mouse, rat and human nuclear extracts that recognize the region containing the core promoter sequence have similar molecular masses and are not identical to the previously described protein factor TIF-1B. Two factors that bind the "spacer" promoter region differ from the factors of the core promoter. "Spacer" promoter factors of mouse and rat nuclear extracts are probably identical, but differ from those of human extract. Protein factors, recognizing the putative enhancer region of rat and human extracts are alike but were not detected in mouse extract. Regions of nontranscribed spacer containing dispersed and tandem repeats do not bind any specific protein factors.
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PMID:[Protein factors specifically binding to the regulatory elements of non-transcribed spacer of rat ribosomal genes]. 260 40

1. When U50 was given to rats over 5 d by twice-daily s.c. injection (but not when delivered by osmotic minipump), buprenorphine and naloxone each precipitated strong, qualitatively distinct, behavioral syndromes. 2. The same dose of buprenorphine provoked similar behaviors in rats given chronic U50 and chronic TIF (analogous s.c. injection protocols), suggestive of neuroadaptation to kappa agonists as a class. This adaptation clearly contrasts with that to chronic mu agonists. 3. The buprenorphine-induced syndrome was characterized by oral stereotypies which had an onset of about 5 min and a duration greater than 4 hr. The intensity was dependent on the dose of agonist injected. 4. The naloxone-induced syndrome was characterized by repetitive yawning and writhing. 5. If oral stereotypy, yawning and writhing are considered to represent an abstinence syndrome, then it will be necessary to use multiple or more selective kappa antagonists to fully unveil kappa dependence in the rat. 6. The present data indicate a strong trend toward the parallel development of tolerance in rats given a similar course of chronic U50 injections as those tested for physical dependence.
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PMID:Neuroadaptation of rats to kappa agonists U-50,488 and tifluadom. 284 2

In herpes simplex virus-infected cells, gene expression is tightly regulated. In this review, we compare the properties of two trans-activating factors which regulate the expression of viral genes. The first, alpha trans-inducing factor (alpha TIF) is a structural component which induces the 5 alpha genes, the first set of genes transcribed after infection. Alpha TIF requires for induction a cis-acting site present in promoter-regulatory domains of all alpha genes. The cis site binds 2 host proteins, alpha H1 and alpha H2-alpha H3. These host proteins have a maximum bound molecular weight of 110,000 and 64,000, respectively. DNase 1 protection assays indicate that alpha H1 protects the entire cis site, whereas alpha H2-alpha H3 binds the 3' domain of the cis site. The methylation interference assays indicate that the contact points of alpha H1 and alpha H2-H3 are at the 5' and 3' termini of the cis site, respectively. Both proteins can bind to the cis site concurrently. Alpha TIF does not bind directly to DNA but was shown to be present in DNA-protein complexes. The binding of alpha TIF to these DNA-protein complexes requires the participation of alpha H1. In contrast to alpha TIF, the product of the alpha 4 gene, a protein 163,000 in apparent molecular weight binds to DNA directly and regulates genes both positively and negatively. The data indicate that alpha 4 protein can bind to at least 2 binding sites differing in nucleotide sequence and which can be present in promoters, across the transcription initiation sites, and in 5' transcribed non-coding sequences. The regulatory functions of the alpha 4 protein may reflect both the nature and location of the binding site. The biological implications of the viral trans-acting proteins are discussed.
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PMID:The trans-activation of herpes simplex virus gene expression: comparison of two factors and their cis sites. 285 7

The herpes simplex virus 1 genes form at least five groups (alpha, beta 1, beta 2, gamma 1, and gamma 2) whose expression is coordinately regulated and sequentially ordered in a cascade fashion. In productively infected cells, the alpha genes are expressed first, and a virion protein, the alpha-trans-inducing factor (alpha-TIF), acts in trans to enhance their expression. Induction of the alpha genes by alpha-TIF requires the presence of a trans-induction cis-acting site (alpha-TIC), and one to three homologs of the alpha-TIC sequence are contained in the regulatory domains of all alpha genes. We report that small DNA fragments from regulatory domains of alpha 0, alpha 4, and alpha 27 genes containing alpha-TIC homologs formed complexes with host but not viral proteins. DNase protection studies indicated that the major host protein complex alpha-H1 detected in DNA gel retardation assays bound asymmetrically across the alpha-TIC site. All DNA fragments containing alpha-TIC homologs, but not those lacking the homolog, competed for the binding of this complex. The location of the binding site of the other host proteins is not yet known. Simian virus 40 DNA fragments containing a homolog of the alpha-TIC sequence also competed with herpes simplex virus DNA fragments carrying authentic alpha-TIC homologs for the alpha-H1 protein complex.
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PMID:Host cell proteins bind to the cis-acting site required for virion-mediated induction of herpes simplex virus 1 alpha genes. 302 64

Herpes simplex viruses encode a structural protein which induces, in trans, expression of alpha genes, the first set of genes to be expressed after infection of permissive cells. This protein, designated as the alpha-trans-inducing factor (alpha-TIF), maps within the BamHI F fragment, and its gene has been sequenced. In the course of mapping the domain of the alpha-TIF gene, it was noted that the intact BamHI fragment was consistently more effective than the complete domain of the alpha-TIF gene in inducing expression of alpha genes. Cotransfections of DNA fragments containing an alpha indicator gene and the alpha-TIF gene with various regions of the BamHI F DNA fragment revealed that the sequences located 3' to the alpha-TIF gene raised the activity of the alpha-TIF gene to nearly the same level as that of the intact BamHI F fragment. The nucleotide sequence and S1 nuclease mapping analyses revealed the presence of two transcribed open reading frames capable of encoding polypeptides with translated molecular weights of 77,357 and 70,527. To determine whether the effect of these sequences in trans on alpha-TIF-mediated induction of alpha genes was due to expression of these genes or competition for transcriptional factors, we constructed plasmids that contained both genes. Into each or both of these genes we inserted, near the translation initiation sites, 14-base-pair linkers carrying translational stop codons (TAG) in all three reading frames. Analyses of these plasmids indicated that the gene encoding the 70,527-molecular-weight polypeptide reduced alpha-TIF-dependent induction of alpha genes, whereas the gene encoding the 77,357-molecular-weight polypeptide increased this activity. Insertion of the stop codons abolished these activities.
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PMID:Characterization and nucleotide sequence of two herpes simplex virus 1 genes whose products modulate alpha-trans-inducing factor-dependent activation of alpha genes. 302 33

The immediate-early promoters of herpes simplex virus give rise to the first series of transcripts after infection. These promoters are composed of compound sequence elements that govern basal level and regulated transcription. The response of three core (truncated) promoters from the herpes simplex virus type 1 IE-4, IE-0, and IE-27 genes to a battery of virus-encoded trans-acting proteins was examined in a short-term transient expression assay system. The results of this study reveal (i) a role for a sequence, 5'---GGGGG---3', flanked by 3 to 5 base pairs of symmetry (the G box), which is present in the upstream region of all immediate-early gene promoters, (ii) a requirement for the consensus sequence protected by ICP4 for autoregulation by this immediate-early gene product, and (iii) an alternative, sequence-independent mechanism for the augmentation of alpha gene expression by the virion-associated transcriptional activator Vmw65, now designated as TIF.
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PMID:Dissection of immediate-early gene promoters from herpes simplex virus: sequences that respond to the virus transcriptional activators. 304 Oct 38


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