Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.5.1.18 (glutathione S-transferase)
 22,582 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The human Alpha glutathione S-transferase gene corresponding to the human liver cDNA clone pGTH2 was isolated from a cosmid genome library. The gene, represented by the clone cosGTH2, spans nearly 12 kb and contains seven exons. The intron/exon borders conform to the standard rules, and an open reading frame is present, starting at position 67 in exon 2, the double-stop codon being at position 733 in exon 7. Exons 1, 2 and 7 differ in length from the known rat gene coding for the Ya enzyme. A 209 bp 5'-upstream region contains TATA and CAT boxes and, in addition, motifs for Sp1-, NF1- and HNFI-binding factors. Clone cosGTH2 represents the less basic subunit, alpha y, of two Alpha glutathione S-transferase subunits (alpha x and alpha y) expressed in liver, which is identical with the kidney subunit alpha 2.
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PMID:Cloning, sequencing and characterization of the human alpha glutathione S-transferase gene corresponding to the cDNA clone pGTH2. 149 29

The complete human genomic glutathione-S-transferase-pi gene (GST-pi) was isolated from a lambda Charon 4A bacteriophage library which was screened by hybridization to a human GST-pi cDNA. We have sequenced 4261 bp which include the entire GST-pi gene as well as over 1200 bp of the 5' and 200 bp of the 3' flanking regions. The GST-pi gene has 7 exons and 6 introns contained within approximately 2.8 kilobases. Primer extension experiments identified four possible transcription start points closely spaced between 29 and 33 nucleotides (nt) 5' to the start of translation. Analysis of the GST-pi promoter region revealed 4 putative transcription regulatory motifs; these sequences include a 'TATA' box 29 bp upstream from the major transcription start point (nt position -29), 2 Sp1 recognition sequences (GGGCGG, nt positions -46 to -41 and -56 to -51), and an AP-1 recognition sequence (TGACTCA, nt positions -69 to -63). The first 200 nt 5' to the start point of transcription contain a G + C-rich region (79%). Additionally, an intriguing A + T-rich region was found between nt positions -505 and -413 which contained 17 AAAAT tandem repeats. Comparison of the GST-pi gene with the homologous rate gene, GST-P, disclosed extensive conservation of genomic organization between the two species.
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PMID:Structure of the human genomic glutathione S-transferase-pi gene. 254 32

We previously showed that v-Rel, the oncoprotein of the avian retrovirus Rev-T, can increase expression from promoters containing binding sites for the cellular transcription factor Sp1 in chicken embryo fibroblasts (S. Sif, A.J. Capobianco, and T.D. Gilmore, Oncogene 8:2501-2509, 1993). In those experiments, v-Rel appeared to increase the transactivating function of Sp1; that is, v-Rel stimulated transactivation by a GAL4-Sp1 protein that lacked the Sp1 DNA-binding domain. We have now shown that in vitro-synthesized v-Rel and GAL4-Sp1 form a complex that can be immunoprecipitated with either anti-Sp1 or anti-v-Rel antiserum. We have also shown that a glutathione S-transferase (GST)-Sp1 fusion protein can specifically interact with in vitro-translated v-Rel and with in vivo-synthesized v-Rel from transformed chicken spleen cells. In addition, we have found that the abilities of wild-type and two mutant forms of v-Rel to increase transactivation by Sp1 in vivo correlate with their abilities to interact with Sp1 in vitro. The sequences important for the interaction of v-Rel with Sp1 in vitro have been mapped to the first 147 amino acids of v-Rel. Other Rel proteins, such as c-Rel, RelA, p52, and p50, were also able to form a complex with Sp1 in vitro. These results suggest that v-Rel increases expression from Sp1 site-containing promoters by functionally interacting with Sp1 and that cellular Rel proteins and Sp1 are likely to interact to influence transcription from natural promoters.
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PMID:Interaction of the v-Rel oncoprotein with cellular transcription factor Sp1. 793 95

The promoter of the human ETS1 gene contains binding site motifs for transcription factors Sp1, Ap1, Ap2, ETS, PEA3 and Oct. It has been shown previously that Ap1, Ap2, and ETS are positive regulators for the transcription of the ETS1 gene and that the ETS1 gene is autoregulated. In addition, two regions on the ETS1 promoter that contain negative regulatory sequences have also been identified. In this study, GST/PEA3 and GST/ets1 fusion proteins were used in gel mobility assays to analyse the interaction between these transcription factors with the binding motifs of PEA3 and ETS in the ETS1 promoter. Promoter constructs in which the binding site motifs are mutated were used to examine the effect of mutation on the activities of transcription factors PEA3, ets1 and Oct. Reporter plasmids containing different deletion mutants of the ETS1 promoter were used to examine the effect of different transcription factors (PEA3, Oct 1 and Oct 2) upon the expression of the ETS1 gene. The results of these studies indicate that PEA3 is a strong positive regulator of the ETS1 promoter and that other transcription factors increase the activity of the ETS1 promoter in an additive rather than synergistic fashion.
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PMID:PEA3, Oct 1 and Oct 2 positively regulate the human ETS1 promoter. 824 40

We report the sequences of two coordinately induced murine glutathione transferase genes, mGSTM1 (GT8.7, Yb1) and mGSTM3 (GT9.3). Genomic clones covering the entire mGSTM1 gene were isolated; comparison of the mGSTM1 gene with genomic sequences from rat class-mu glutathione transferase genes suggests that the mGSTM1 gene is orthologous to the rGSTM1 (rat3, Yb1) gene. The start of mGSTM1 mRNA transcription was mapped by primer extension and RNase protection to 37 nucleotides upstream from the initiation codon. The 160 nucleotides 5'-proximal to the start of transcription match exactly the 5'-end of the class-mu glutathione transferase cDNA clone pmGT10. An mRNA transcript was found approximately 2.0 kb upstream from the start of mGSTM1 transcription; its sequence does not show significant similarity to other sequences in the DNA or protein sequence databases. The mGSTM1 gene contains a TATAAA sequence at -31 nucleotides upstream from the start of transcription, but no exact match to the antioxidant response element (RGTGACNNNGC), the xenobiotic response element (TNGCGTG), or the AP-1 consensus (TGASTMA) is found in the 5'-flanking region, although near matches are found in the 5'-flanking region, in intron 1, and in other parts of the gene. A genomic clone containing the first five exons of the mGSTM3 gene was also isolated. The mGSTM3 gene contains several repetitive elements--two upstream from the start of transcription and one within intron 2--that disrupt its similarity with the mGSTM1 gene. The 5'-flanking sequence of the mGSTM3 gene does not contain a TATAAA sequence or any exact matches to ARE or XRE consensus sequences, although an Sp1 binding site is found at -66. mGSTM3 and mGSTM1 diverge substantially outside their exons and share less than 60% sequence identity in the 5'-flanking region. Thus, it is likely that the mGSTM1-mGSTM3 gene duplication predates the rat-mouse divergence. The strongest region of conservation between the mGSTM1 gene and the mGSTM3 gene occurs in exon 3, intron 3, and exon 4; this region also shares strong similarity with the rGSTM1 (rat3, Yb1) and rGSTM2 (rat4, Yb2) genes.
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PMID:The structure of two murine class-mu glutathione transferase genes coordinately induced by butylated hydroxyanisole. 851 23

Within the region around 150 bp upstream of the initiation codon, which was previously shown to suffice for growth-regulated expression, the murine thymidine kinase gene carries a single binding site for transcription factor Sp1; about 10 bp downstream of this site, there is a binding motif for transcription factor E2F. The latter protein appears to be responsible for growth regulation of the promoter. Mutational inactivation of either the Sp1 or the E2F site almost completely abolishes promoter activity, suggesting that the two transcription factors interact directly in delivering an activation signal to the basic transcription machinery. This was verified by demonstrating with the use of glutathione S-transferase fusion proteins that E2F and Sp1 bind to each other in vitro. For this interaction, the C-terminal part of Sp1 and the N terminus of E2F1, a domain also present in E2F2 and E2F3 but absent in E2F4 and E2F5, were essential. Accordingly, E2F1 to E2F3 but not E2F4 and E2F5 were found to bind sp1 in vitro. Coimmunoprecipitation experiments showed that complexes exist in vivo, and it was estabilished that the distance between the binding sites for the two transcription factors was critical for optimal promoter activity. Finally, in vivo footprinting experiments indicated that both the sp1 and E2F binding sites are occupied throughout the cell cycle. Mutation of either binding motif abolished binding of both transcription factors in vivo, which may indicate cooperative binding of the two proteins to chromatin-organized DNA. Our data are in line with the hypothesis that E2F functions as a growth- and cell cycle regulated tethering factor between Sp1 and the basic transcription machinery.
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PMID:Interaction of Sp1 with the growth- and cell cycle-regulated transcription factor E2F. 865 41

Synaptobrevin II is a small integral membrane protein of synaptic vesicles that plays a key role in exocytosis. The 5'-flanking region of the human synaptobrevin II gene is very (G+C)-rich and contains a 13-bp motif that includes overlapping binding sites for the zinc finger transcription factors Sp1 and zif268/egr-1. To test whether Sp1 and zif268/egr-1 interact with this motif, gel retardation assays were performed. These assays revealed that both transcription factors bind to the (G+C)-rich motif of the synaptobrevin II gene in vitro. The binding of Sp1 was additionally confirmed by supershift analysis with antibodies specific for Sp1. To determine whether zif268/egr-1 plays a role in controlling synaptobrevin II gene expression, a plasmid was constructed containing the (G+C)-rich motif of the synaptobrevin II gene upstream of a minimal promoter and the Escherichia coli chloramphenicol acetyltransferase (CAT) gene as a reporter. This plasmid was transfected into CHO-K1 cells together with an expression vector encoding zif268/egr-1. Zif268/egr-1 failed to activate transcription from this reporter gene, although it transactivated a reporter gene containing an identical (G+C)-rich motif derived from the human synapsin I promoter. Overexpression of Sp1, however, clearly activated transcription of a reporter gene under the control of the synaptobrevin II promoter (G+C)-rich sequence in Drosophila SL2 cells, which provided an Sp1-deficient background. Furthermore, a glutathione S-transferase protein containing the DNA-binding domain of Sp1 was shown to function as a dominant negative form of Sp1, reducing transcription of the synaptobrevin II promoter-CAT reporter gene in mammalian cells to basal levels. From these data, we conclude that the zif268/egr-1-binding site in the synaptobrevin II promoter is not functionally active. Instead, an overlapping Sp1-binding site in this (G+C)-rich region clearly mediates constitutive transcriptional activation.
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PMID:Role of zinc-finger proteins Sp1 and zif268/egr-1 in transcriptional regulation of the human synaptobrevin II gene. 877 32

The transcription factor Sp1 plays an important role in the expression of many cellular genes. In studies of proteins that associate with Sp1, a 62-kDa glycoprotein was found in immunoprecipitates of Sp1. This protein was detected in these immunoprecipitates by the monoclonal antibody, RL2, which was originally raised against nuclear pore proteins but was subsequently found to recognize an epitope that contains O-linked N-acetylglucosamine (O-GlcNAc). The association of this protein with Sp1 could be blocked by SDS denaturation of the protein complex. Western blot analysis of the Sp1 immunoprecipitate using antibodies to p62 nucleoporin indicated that this nuclear pore protein associates with Sp1. Furthermore, immunoprecipitation of p62 nucleoporin resulted in the coprecipitation of Sp1. Recombinant p62, expressed as a GST-fusion protein using a vaccinia virus system, also interacted with both recombinant and native Sp1. This interaction between p62 and Sp1 required the C-terminus of p62 and the C-terminus was able to bind Sp1, albeit less efficiently than native p62. A mammalian two-hybrid interaction assay was devised in which p62 was fused to the Gal4 DNA-binding domain. This system also indicated that p62, through its C-terminus, interacts with Sp1 in the living cell. We propose that this interaction of a nuclear pore protein with Sp1 may reflect the nuclear organization required to bring transcribable DNA in contact with the transcription factors.
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PMID:Interaction of the transcription factor Sp1 with the nuclear pore protein p62 requires the C-terminal domain of p62. 940 13

The HIV-1 promoter was used as a model to identify transcription factors involved in LPS-dependent transcription in RAW 264 murine macrophages. Expression plasmids for Ets-2 and PU.1 trans-activated the HIV-1 LTR and recombinant PU.1 and an Ets-2 DNA binding domain/GST fusion protein bound to the 5' kappa B site of the HIV-1 enhancer. Ets-2 mRNA was LPS-inducible in RAW 264 cells and LPS stimulated phosphorylation of threonine 72 residue within the Ets-2 pointed domain. Induction of Ets-2 and other LPS-responsive transcription factors was also observed upon addition of plasmid DNA, which complicates interpretation of transient transfections. The proximal promoter region, containing two Sp1 sites, was also LPS-responsive. We propose that the kappa B elements and the tandem Sp1 sites act as LPS response elements and that kappa B-mediated LPS action involves Ets and rel factors.
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PMID:Involvement of Ets, rel and Sp1-like proteins in lipopolysaccharide-mediated activation of the HIV-1 LTR in macrophages. 965 43

Fibronectin (FN) is an extracellular matrix protein that connects the extracellular matrix to intracellular cortical actin filaments through binding to its cell surface receptor, alpha5beta1, a member of the integrin superfamily. The expression level of FN is reduced in most tumor cells, facilitating their anchorage-independent growth by still unclarified mechanisms. The cDNA clone encoding G-rich sequence binding protein G10BP-1, which is responsible for repression of the rat FN gene, was isolated by using a yeast one-hybrid screen with the G10 stretch inserted upstream of the HIS3 and lacZ gene minimal promoters. G10BP-1 comprises 385 amino acids and contains two basic regions and a putative zipper structure. It has the same specificity of binding to three G-rich sequences in the FN promoter and the same size as the G10BP previously identified in adenovirus E1A- and E1B-transformed rat cells. Expression of G10BP-1 is cell cycle regulated; the level was almost undetectable in quiescent rat 3Y1 cells but increased steeply after growth stimulation by serum, reaching a maximum in late G1. Expression of FN mRNA is inversely correlated with G10BP-1 expression, and the level decreased steeply during G1-to-S progression. This down regulation was strictly dependent on the downstream GC box (GCd), and base substitutions within GCd abolished the sensitivity of the promoter to G10BP-1. In contrast, the level of Sp1, which competes with G10BP for binding to the G-rich sequences, was constant throughout the cell cycle, suggesting that the concentration of G10BP-1 relative to that of Sp1 determines the expression level of the FN gene. Preparation of glutathione S-transferase pulldowns of native proteins from the cell extracts containing exogenously or endogenously expressed G10BP-1, followed by Western blot analysis, showed that G10BP-1 forms homodimers through its basic-zipper structure.
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PMID:Cloning and characterization of a GC-box binding protein, G10BP-1, responsible for repression of the rat fibronectin gene. 967 87


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