Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P51532 (transcriptional activator)
 6,546 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cells were transfected with luciferase reporter genes, under the control of promoters derived from either the farnesyl diphosphate (FPP) synthase, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) synthase, HMG-CoA reductase, or low density lipoprotein receptor genes. The increase in luciferase activity that occurred when cells were either incubated in sterol-depleted medium or cotransfected with a cDNA encoding sterol regulatory element-binding protein (SREBP)-1a was prevented by coexpression of wild-type E1A or a Gal4-CBP (1-451) fusion protein. The inhibitory effect of E1A was overcome by coexpression of CBP. The increase in reporter gene activity noted above was not affected when the cells were cotransfected with cDNAs that encoded either a mutant E1A that is unable to interact with the transcriptional activator CBP or Gal4-CBP fusion proteins encoding separate fragments of CBP, which span the remainder of the CBP molecule. A preformed SREBP-1a:[32P]DNA complex bound specifically to membrane-immobilized GST-CBP fusion proteins that contained amino-terminal portions of CBP. In order to investigate the role of CBP in the regulation of endogenous genes, we isolated stable transformants that express Gal4-CBP(1-451) in response to added doxycycline. Induction of endogenous FPP synthase and HMG-CoA synthase mRNAs, in response to cellular cholesterol depletion, was prevented when cells expressed Gal4-CBP(1-451). We conclude that when cells are incubated in the absence of sterols, the transcriptional activation of the HMG-CoA synthase, HMG-CoA reductase, FPP synthase, and low density lipoprotein receptor genes is dependent on a specific interaction between SREBP, which is bound to the promoter DNA, and the amino-terminal domain (amino acids 1-451) of CBP.
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PMID:CBP is required for sterol-regulated and sterol regulatory element-binding protein-regulated transcription. 965 91

As a first step to elucidate the functions of Schizosaccharomyces pombe (S. pombe) GATA factors, we have isolated the gaf1+ gene (GATA-factor like gene) in S. pombe. The predicted amino acid (aa) sequence of Gaf1 reveals a single zinc finger domain typical of fungal GATA factors, and the zinc finger exhibits 60% aa identity to that of human GATA-1. The open reading frame of Gaf1 predicts a protein of Mr 32 kDa consisting of 290 intronless amino acids. Disruption of this gene has no effect on cell viability and growth rate. The GST-Gaf1 fusion protein binds specifically to GATA motifs of its own promoter as well as DAL7 UAS, a canonical GATA motif of Saccharomyces cerevisiae (S. cerevisiae) The specific DNA-binding activity resides within the N-terminal half of Gaf1 (Gaf1N; aa 1-120) containing the zinc finger, whereas the C-terminal half (Gaf1C; aa 121-290) contains transactivation sequences that induce the expression of the lacZ reporter when fused to the GAL4 DNA binding domain. These results demonstrate that Gaf1 may function as a transcriptional activator consisting of DNA-binding and transactivation domains.
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PMID:Molecular cloning of gaf1, a Schizosaccharomyces pombe GATA factor, which can function as a transcriptional activator. 971 31

Activation of transcription at bacteriophage T4 late promoters and coupling of late transcription to concurrent replication requires a peculiar transcriptional activator, the gp45 sliding clamp of the T4 DNA polymerase. In order to activate transcription, the topologically DNA-linked trimeric gp45 must interact with two T4-encoded RNA polymerase-binding proteins, the gp33 co-activator, and the gp55 late sigma factor. The carboxy termini of gp55 and gp33 share a similar sequence, which has been shown to be required for response of late transcription to activation by gp45. Alanine-scanning mutagenesis of the C terminus of gp55 shows that residues within the short hydrophobic sequence L(D/A)FLYE, are necessary for gp55 to bind to gp45, and to respond maximally to transcriptional activation by gp45. When fused to GST, the peptide SLDFLYE suffices for specific gp45 binding. Thus, it constitutes the main gp55 epitope for gp45 interaction.
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PMID:Activator-sigma interaction: A hydrophobic segment mediates the interaction of a sigma family promoter recognition protein with a sliding clamp transcription activator. 981 12

Biological, molecular, and epidemiological data have demonstrated that human T cell leukemia virus type 1 (HTLV-1) encoded Tax protein plays a central role in the initiation of T cell malignancy. The 40-kDa Tax oncoprotein serves as a potent transcriptional activator that induces viral gene expression driven by the HTLV-1 long terminal repeats and also stimulates multiple cellular genes involved in T cell activation, cell cycle regulation, and gene activation. Since Tax has been shown to interact directly and indirectly with the NF-kappa B/I kappa B regulatory proteins, we examined the significance of an in vivo association between Tax and the I kappa B alpha inhibitor. Using GST affinity chromatography, Tax was shown to interact with the I kappa B alpha ankyrin repeats which are essential for interaction with the NF-kappa B/Rel proteins. In vivo, using I kappa B alpha mutants and co-immunoprecipitation, a preferential interaction between HTLV-1 Tax and N-terminally hypophosphorylated I kappa B alpha was detected. Tax also enhanced binding of I kappa B alpha to the proteasome subunit HsN3, resulting in a Tax-enhanced, constitutive degradation of wild-type and mutated forms of I kappa B alpha in the absence of phosphorylation and ubiquitination. Binding of I kappa B alpha to proteasome subunit HC9 was also observed, but this interaction occurred independently of Tax. Taken together, these results suggest a role for Tax as a viral chaperone resulting in the enhanced constitutive turnover of I kappa B alpha. The association of Tax with hypophosphorylated I kappa B alpha may prevent I kappa B alpha from binding to NF-kappa B and also target I kappa B alpha to the proteasome for degradation via a phosphorylation-independent pathway.
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PMID:Association between HTLV-1 Tax and I kappa B alpha is dependent on the I kappa B alpha phosphorylation state. 987 28

Brachyury is a sequence-specific transcriptional activator that is essential for notochord differentiation in a variety of chordates. In vertebrates, Brachyury is expressed throughout the presumptive mesoderm, but becomes restricted to the notochord at later stages of development. In ascidians, such as Ciona intestinalis, Brachyury is expressed exclusively in the notochord and does not exhibit an early pan-mesodermal pattern. Subtractive hybridization screens were recently used to identify potential Ciona Brachyury (Ci-Bra) target genes (Takahashi, H., Hotta, K., Erives, A., Di Gregorio, A., Zeller, R. W., Levine, M. and Satoh, N. (1999). Genes Dev. 13, 1519-1523). Of the genes that were identified in this screen, one corresponds to a new member of the tropomyosin superfamily, Ciona tropomyosin (Ci-trop). Here we show that Ci-trop is specifically expressed in the developing notochord beginning at gastrulation, and expression persists in the notochord during tailbud and tadpole stages. A 3 kb region of the Ci-trop 5'-flanking sequence was characterized via electroporation of lacZ fusion genes into fertilized Ciona eggs. A minimal, 114 bp enhancer was identified that is sufficient to direct the expression of a heterologous promoter in the notochord. DNA binding assays indicate that this enhancer contains two sets of low-affinity Brachyury half-sites, which are bound in vitro by a GST/Ci-Bra fusion protein. Deletion of the distal sites inactivates the notochord-specific staining pattern mediated by an otherwise normal Ci-trop/lacZ transgene. These results suggest that Ci-trop is a direct target gene of Ci-Bra and that Brachyury plays an immediate role in the cellular morphogenesis of the notochord.
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PMID:Regulation of Ci-tropomyosin-like, a Brachyury target gene in the ascidian, Ciona intestinalis. 1057 37

The cucumber mosaic virus (CMV)-encoded 2b protein has been implicated to play a role in long distance movement of the virus through the plant's transport system. It is unknown, however, how it mediates virus movement and whether any intrinsic components of plant cells also participate in this process. To isolate a host factor that interacts with 2b, the yeast two-hybrid system was used. First, it was found that the 2b protein per se could function as a transcriptional activator in yeast. However, its two carboxyl terminal deletion mutants, 2bdelta98 and 2bdelta95, which lacked 12 and 15 amino acids from the carboxyl terminus respectively, showed complete absence of transcriptional activation in yeast. A tobacco cDNA library expressing the GAL4 activation domain fusion proteins was screened using 2bdelta98 as a bait. A clone named 2bip (2b-interacting protein) was isolated whose translation product apparently interacted with 2b. Consistent with this observation, bacterially expressed GST-2bip fusion protein bound tightly to 2bdelta95 and 2bdelta98 polypeptides in vitro, as well as to the unmodified 2b protein. Nucleotide sequencing and database searches revealed that the amino acid sequence deduced from it was similar to a prokaryotic LytB protein and an unknown protein of Arabidopsis. DNA and RNA gel blot analyses showed that 2bip-related sequences were present in the tobacco genome and that transcripts corresponding to 2bip were expressed constitutively in various plant organs and in response to CMV infection. These results suggest 2bip as a novel host factor that is capable of interacting with CMV2b.
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PMID:Isolation of a putative tobacco host factor interacting with cucumber mosaic virus-encoded 2b protein by yeast two-hybrid screening. 1059 45

EBNA2 is essential for Epstein-Barr virus (EBV) immortalization of B lymphocytes. EBNA2 functions as a transcriptional activator and targets responsive promoters through interaction with the cellular DNA binding protein CBF1. We have examined the mechanism whereby EBNA2 overcomes CBF1-mediated transcriptional repression. A yeast two-hybrid screen performed using CBF1 as the bait identified a protein, SKIP, which had not previously been recognized as a CBF1-associated protein. Protein-protein interaction assays demonstrated contacts between SKIP and the SMRT, CIR, Sin3A, and HDAC2 proteins of the CBF1 corepressor complex. Interestingly, EBNA2 also interacted with SKIP in glutathione S-transferase affinity and mammalian two-hybrid assays and colocalized with SKIP in immunofluorescence assays. Interaction with SKIP was not affected by mutation of EBNA2 conserved region 6, the CBF1 interaction region, but was abolished by mutation of conserved region 5. Mutation of conserved region 5 also severely impaired EBNA2 activation of a reporter containing CBF1 binding sites. Thus, interaction with both CBF1 and SKIP is necessary for efficient promoter activation by EBNA2. A model is presented in which EBNA2 competes with the SMRT-corepressor complex for contacts on SKIP and CBF1.
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PMID:A role for SKIP in EBNA2 activation of CBF1-repressed promoters. 1064 67

Octamer transcription factor-1 (Oct-1) is a member of the POU (Pit-1, Oct-1, unc-86) family of transcription factors and is involved in the transcriptional regulation of a variety of gene expressions related to cell cycle regulation, development, and hormonal signals. It has been shown that Oct-1 acts not only as a transcriptional activator but also as a transcriptional repressor for certain genes. The mechanism of the repressive function of Oct-1 has not been well understood. Here we demonstrate by using the glutathione S-transferase pull-down assays and coimmunoprecipitation assays that the POU domain of Oct-1 directly interacts with a silencing mediator for retinoid and thyroid hormone receptors (SMRT). The interaction surfaces are located in the C-terminal region of SMRT, which are different from previously described silencing domains I and II or receptor interacting domains I and II. In transient transfection assays in COS1 cells, overexpression of SMRT attenuated the augmentation of Oct-1 transcriptional activity by OBF-1/OCA-B, activator for Oct-1. In pull-down assays, increasing amounts of SMRT could compete the binding of OCA-B to Oct-1 POU domain. The activity of Oct-1 could be determined by a regulated balance between SMRT and OCA-B. Furthermore, cotransfected unliganded thyroid hormone receptor enhanced the transactivation by Oct-1, and addition of 3,3',5-tri-iodo-l-thyronine obliterated the stimulatory effects. Consequently, in the presence of cotransfected thyroid hormone receptor, the octamer response element acts as an element negatively regulated by 3,3',5-tri-iodo-l-thyronine. The results suggest that the transcriptional activity of Oct-1 can be modulated by interaction through its POU domain by a silencing mediator SMRT resulting in the cross-talk between Oct-1 and nuclear receptors.
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PMID:Silencing mediator for retinoid and thyroid hormone receptors interacts with octamer transcription factor-1 and acts as a transcriptional repressor. 1113 19

OsMADS1 is a MADS box gene controlling flower development in rice. In order to learn more about the function of OsMADS1, we searched for cellular proteins interacting with OsMADS1 employing the yeast two-hybrid system. Two novel proteins with MADS domains, which were named OsMADS14 and OsMADS15, were isolated from a rice cDNA library. OsMADS14 and -15 are highly homologous to the maize MADS box gene ZAP1 which is an orthologue of the floral homeotic gene APETALA1 (AP1). Interactions among the three MADS domain proteins were confirmed by in vitro experiments using GST-fused OsMADS1 expressed in Escherichia coli and in vitro translated proteins of OsMADS14 and -15. We determined which domains in OsMADS1, -14, and -15 were required for protein-protein interaction employing the two-hybrid system and pull-down experiments. While the K domain was essential for protein-protein interaction, a region preceded by the K domain augmented this interaction. Interestingly, the C-terminal region of OsMADS1 functioned as a transcriptional activation domain in yeast and mammalian cells, while, on the other hand, the C domains of OsMADS14 and -15 exhibited only very weak transcriptional activator functionality, if any at all.
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PMID:Two rice MADS domain proteins interact with OsMADS1. 1119 26

The yeast Mediator is composed of two subcomplexes, Rgr1 and Srb4, known to be required for diverse aspects of transcriptional regulation; however, their structural and functional organizations have not yet been deciphered in detail. Biochemical analyses designed to determine the subunit composition of the Rgr1 subcomplex revealed that the regulator-interacting subcomplex has a modular structure and is composed of the Gal11, Med9/Cse2, and Med10/Nut2 modules. Genome-wide gene expression and Northern analyses performed in the presence or absence of the various Mediator modules revealed a distinct requirement for the Gal11, Med9/Cse2, and Med10/Nut2 modules in transcriptional repression as well as activation. GST pull-down analysis revealed that the transcriptional repressor Tup1 binds to distinct but overlapping regions of the Gal11 module that were shown previously to be transcriptional activator binding sites. These data suggest that competition between transcriptional activators and repressors for a common binding site in the Mediator and distinct conformational changes in the Mediator induced by repressor binding may underlie the mechanism of transcriptional repression in eukaryotes.
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PMID:Med9/Cse2 and Gal11 modules are required for transcriptional repression of distinct group of genes. 1147 Jul 94


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