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 775-amino-acid IE110 (or ICP0) phosphoprotein of herpes simplex virus (HSV) functions as an accessory transcription factor during the lytic cycle and plays a critical role in reactivation from latent infection. By immunofluorescence analysis, IE110 localizes in a novel pattern consisting of several dozen spherical punctate granules in the nuclei of DNA-transfected cells. We constructed a hybrid version of IE110 that contained an epitope-tagged domain from the N terminus of the HSV IE175 protein and lacked the IE110 N-terminal domain that confers punctate characteristics. This hybrid IE175(N)/IE110(C) protein gave an irregular nuclear diffuse pattern on its own but was redistributed very efficiently into spherical punctate granules after cotransfection with the wild-type HSV-1 IE110 protein. Similar colocalization interactions occurred with internally deleted forms of IE110 that lacked the zinc finger region or large segments from the center of the protein, including both cytoplasmic and elongated punctate forms, but C-terminal truncated versions of IE110 did not interact. In all such interactions, the punctate phenotype was dominant. Evidence that C-terminal segments of IE110 could also form stable mixed-subunit oligomers in vitro was obtained by coimmunoprecipitation of in vitro-translated IE110 polypeptides with different-size hemagglutinin epitope-tagged forms of the protein. This occurred only when the two forms were cotranslated, not when they were simply mixed together. An in vitro-synthesized IE110 C-terminal polypeptide also gave immunoprecipitable homodimers and heterodimers when two different-size forms were cross-linked with glutaraldehyde and reacted specifically with a bacterial glutathione S-transferase/IE110 C-terminal protein in far-Western blotting experiments. The use of various N-terminal and C-terminal truncated forms of IE110 in the in vivo assays revealed that the outer boundaries of the interaction domain mapped between codons 617 and 711, although inclusion of adjacent codons on either side increased the efficiency severalfold in some assays. We conclude that the C-terminal region of IE110 contains a high-affinity self-interaction domain that leads to stable dimer and higher-order complex formation both in DNA-transfected cells and in in vitro assays. This segment of IE110 is highly conserved between HSV-1 and HSV-2 and appears to have the potential to play an important role in the interaction with the IE175 protein, as well as in correct intracellular localization, but it is not present in the equivalent proteins from varicella-zoster virus, pseudorabies virus, or equine abortion virus.
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PMID:Identification of a dimerization domain in the C-terminal segment of the IE110 transactivator protein from herpes simplex virus. 815 88

The ability of Epstein-Barr virus (EBV) latent infection nuclear protein EBNA3C to activate transcription of two EBNA2-responsive genes and to inhibit EBNA2 activation of transcription in transient-transfection assays appears to be due to its ability to interact with RBPJkappa, a cell protein that links EBNA2 to its response elements. We now show that EBNA3A and EBNA3B expressed in non-EBV-infected Burkitt tumor lymphoblasts are similar to EBNA3C in binding to glutathione S-transferase-RBPJkappa in vitro and in coimmunoprecipitating from cell lysates with antibody to RBPJkappa. EBNA3A and EBNA3B can also inhibit the interaction of RBPJkappa with cognate DNA in vitro. Although EBNA3 open reading frames are each close to 1,000 codons long, EBNA3A amino acids 1 to 138, EBNA3B amino acids 1 to 311, and EBNA3C amino acids 1 to 183 are sufficient for RBPJkappa interaction, while EBNA3B amino acids I to 109 have less or no binding. The RBPJkappa interacting domains overlap with the most highly conserved domain (amino acids 90 to 320) among the EBNA3 proteins. Thus, the EBNA3 gene family appears to have evolved to differentially regulate promoters with RBPJkappa binding sites. EBNA2, EBNA3A, and EBNA3C are important in EBV transformation of primary human B lymphocytes. Their interaction with RBPJkappa links EBV transformation to the notch signaling pathway and the effects of activated notch in T-cell leukemogenesis.
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PMID:The amino-terminal domains of Epstein-Barr virus nuclear proteins 3A, 3B, and 3C interact with RBPJ(kappa). 862 85

Maintenance of Kaposi's sarcoma-associated herpesvirus (KSHV) latent infection depends on the viral episomes in the nucleus being distributed to daughter cells following cell division. The latency-associated nuclear antigen (LANA) is constitutively expressed in all KSHV-infected cells. LANA binds sequences in the terminal repeat regions of the KSHV genome and tethers the viral episomes to chromosomes. To better understand the mechanism of chromosomal tethering, we performed glutathione S-transferase (GST) affinity and yeast two-hybrid assays to identify LANA-interacting proteins with known chromosomal association. Two of the interactors were the methyl CpG binding protein MeCP2 and the 43-kDa protein DEK. The interactions of MeCP2 and DEK with LANA were confirmed by coimmunoprecipitation. The MeCP2-interacting domain was mapped to the previously described chromatin binding site in the N terminus of LANA, while the DEK-interacting domain mapped to LANA amino acids 986 to 1043 in the C terminus. LANA was unable to associate with mouse chromosomes in chromosome spreads of transfected NIH 3T3 cells. However, LANA was capable of targeting to mouse chromosomes in the presence of human MeCP2 or DEK. The data indicate that LANA is tethered to chromosomes through two independent chromatin binding domains that interact with different protein partners.
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PMID:Protein interactions targeting the latency-associated nuclear antigen of Kaposi's sarcoma-associated herpesvirus to cell chromosomes. 1238 20

The gene encoding a truncated merozoite antigen-2 (EMA-2t) of Babesia equi was cloned and highly expressed in Escherichia coli as a glutathione S-transferase fusion protein (G-rEMA-2t). Both G-rEMA-2t and rEMA-2t (after the removal of glutathione S-transferase) had good antigenicity. Either Western blot analysis with rEMA-2t or enzyme-linked immunosorbent assay (ELISA) with G-rEMA-2t clearly discriminated the sera of horses experimentally infected with B. equi from sera of horses infected with Babesia caballi and healthy horses, although rEMA-2t was not suitable for ELISA, probably owing to its poor absorbability to the plates. The specific antibodies in B. equi-infected horses were detectable during both acute and latent infection (6 to 244 days postinfection). Horse sera from Jilin Province, China, were examined by the two tests. The seroprevalence of B. equi was 49.2% (31 of 63 sera) by Western blot analysis with rEMA-2t and 47.6% (30 of 63 sera) by ELISA with G-rEMA-2t. The correspondence was 98.4% (62 of 63 sera) between the two tests. The results indicate that G-rEMA-2t and rEMA-2t proteins should be suitable antigens for the development of an effective immunodiagnostic assay due to their high sensitivity, specificity, and great yield.
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PMID:High-level expression and purification of a truncated merozoite antigen-2 of Babesia equi in Escherichia coli and its potential for immunodiagnosis. 1262 44

The latent nuclear antigen (LNA) of Kaposi's sarcoma-associated herpesvirus (KSHV) has an essential role in viral latent infection. LNA maintains the stability of KSHV episomes and modulates the expression of cellular genes. A novel cellular protein KLIP1 was identified to interact with LNA through yeast two-hybrid screening, and confirmed by a glutathione S-transferase pull down assay. Domain mapping showed that KLIP1 interacted with the N-terminal domain of LNA. Northern blot hybridization with a KLIP1 probe identified a major transcript of 1.8 kb and a minor transcript of 2.8 kb. cDNA library screening and 5'-RACE revealed that the major transcript encoded an open-reading-frame of 1,257 bp and had a 5'-untranslated region of 73 nucleotides. The major KLIP1 transcript was ubiquitously present in different cell types examined. A KLIP1 synthetic peptide antibody detected a doublet of 58-kDa and 63-kDa proteins in a Western blot assay. KLIP1 had two putative nuclear localization signals and showed punctate nuclear localization when expressed as a GFP-fusion protein. KLIP1 interacted with LNA in vivo, as demonstrated by coimmunoprecipitation using KSHV-infected cells and colocalization when they were expressed as GFP- and DsRed-fusion proteins, respectively. Consistent with its interaction with LNA, nuclear localization, and possession of two leucine zipper motifs, KLIP1 behaved like a transcriptional factor and repressed herpes simplex virus thymidine kinase (TK) promoter activity in a mammalian one-hybrid assay. In addition, cotransfection with LNA alleviated the transcriptional repression effect of KLIP1 on TK promoter activity. These results suggest that KLIP1 is a new member of cellular transcriptional repressors, and that LNA is involved in deregulating cellular transcription process.
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PMID:Identification of a novel cellular transcriptional repressor interacting with the latent nuclear antigen of Kaposi's sarcoma-associated herpesvirus. 1294 84

As only a small portion of smokers develop clinically-apparent COPD, there should be some factors relevant to the susceptibility to smoking. Several studies have demonstrated an increased risk of COPD within families of COPD probands. Recent exploratory studies have revealed a number of candidate genes that may influence a person's risk of COPD, including MMP-9, microsomal epoxide hydrolase, glutathione S-transferase, hemeoxygenase, and TNF-alpha. However, the results from other laboratory are often inconsistent, and there have been no genes except alpha 1-antitrypsin, which have been definitely confirmed to explain the susceptibility to smoking in the development of COPD. It is of note that the susceptibility to smoking could be explained also by non-genetic factors such as adenovirus latent infection to the airways.
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PMID:[Role of genetic factors in the development of COPD]. 1467 16

Chronic obstructive pulmonary disease (COPD) is characterized by irreversible airflow limitation in the lungs. Smoking is one of the amongst major risk factors for the development of COPD. Environmental pollution, age, and airway hyperreactivity are also the risk factors. The protease-antiprotease imbalance and the oxidant-antioxidant imbalance cause airway inflammation and destruction. The genes related to these balances may contribute to development of COPD pathology. Candidate gene-association studies and linkage analyses have been reported for COPD patients. The alpha-1 antitrypsin, glutathione S-transferase, microsomal epoxide hydrolase, and matrix metalloproteinase, are candidate genes. In acquired factors for COPD pathology, the adenoviral latent infection may enhance airway inflammation, leading to airflow obstruction. The current progress and future visions of genetic predisposition of COPD are discussed.
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PMID:1. COPD pathogenesis from the viewpoint of risk factors. 1722 Jun 2