Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.2.1.31 (beta-glucuronidase)
7,680 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Maize cytosolic glyceraldehyde-3-phosphate dehydrogenase (GAPC) is encoded by a small multi-gene family consisting of gpc1, gpc2, gpc3 and gpc4. GAPC3/4 protein is synthesized in roots during anoxic conditions and is known to be one of the 'anaerobic polypeptides'. We further analyzed the gpc gene family by isolating full-length cDNA clones of gpc2, gpc3, gpc4 and genomic clones of gpc2 and gpc4. The deduced amino acid sequence of GAPC4 has 99.4% identity with that of GAPC3 as compared to only 81% with either GAPC1 or GAPC2 amino acid sequence. Based on the deduced amino acid sequence identity we designated GAPC1 and GAPC2 as group I (97% identical) and GAPC3 and GAPC4 as group II (99.4% identical). As previously reported for gpc3, transcript levels were also induced for gpc4 by anaerobiosis. Neither heat shock, cold nor salt stress induced the expression of gpc3 or gpc4. In contrast, the transcript accumulation of gpc1 and gpc2 either remained constitutive or decreased in response to anoxia. The upstream regions of gpc2 and gpc4 contain typical eukaryotic promoter features with transcription start points at 76 and 68 bp upstream of their respective translation initiation sites. Transient expression analysis of gpc4 promoter-beta-glucuronidase (GUS) reporter gene constructs in bombarded maize suspension culture cells was used to examine the role of 5'-flanking sequence of gpc4. The gpc4 promoter (-1997 to +39 bp) was sufficient to induce GUS activity approximately three-fold in response to anaerobiosis. 5'-unidirectional deletion analysis revealed that the critical region of gpc4 required for its induced expression lies between -290 and -157. This region has reverse-oriented putative 'anaerobic response elements', G-box like sequences, and a GC motif similar to that previously defined as a regulatory element of maize adh1 and Arabidopsis adh, as well as the sequences found in other environmentally inducible genes. The relevance of these elements in conferring anaerobic induction of gpc4 gene expression is discussed.
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PMID:Molecular characterization and promoter analysis of the maize cytosolic glyceraldehyde 3-phosphate dehydrogenase gene family and its expression during anoxia. 903 63

Storage of potato (Solanum tuberosum) tubers at 4 degrees C is associated with the accumulation of several transcripts. DNA sequence analysis of cDNA clone CI21, which corresponds to one of the cold-induced transcripts, revealed high homology to transcripts of tomato (Lycopersicon esculentum) and wild potato (Solanum chacoense) induced by ripening and water stress. Two homologous, nonallelic genes, ci21A and ci21B, were isolated and sequenced. Northern blot analysis showed that CI21 transcripts were present at the highest levels in cold-stored tubers, at lower levels in stems and roots, and at the lowest levels in leaves and tubers stored at room temperature. Treatment with abscisic acid, heat, and a high concentration of salt had no marked effect on CI21 transcript levels in tubers and leaves. Drought was the only stress treatment that induced CI21 transcripts in leaves, but it did not do so in tubers. Western blot analysis detected CI21 protein only in tubers. Chimeric gene constructs between the putative ci21A promoter region and the uidA reporter gene were tested in transgenic potato plants for induction of beta-glucuronidase activity by low temperature. A 2-fold increase of beta-glucuronidase activity in response to tuber storage at 4 degrees C was observed for fragments between 380 and 2000 bp of the ci21A promoter region.
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PMID:Expression patterns and promoter activity of the cold-regulated gene ci21A of potato. 904 87

D-Glucaric acid (GA) is a nontoxic, natural compound. One of its derivatives is the potent beta-glucuronidase inhibitor D-glucaro-1,4-lactone (1,4-GL). The goal of this study was to demonstrate the in vivo formation of 1,4-GL from a D-glucarate salt and determine its metabolism, uptake by selected organs, and excretion following oral administration of potassium hydrogen D-[14C]glucarate to male and female Sprague-Dawley rats. 1,4-GL increases detoxification of carcinogens and tumor promoters/progressors by inhibiting beta-glucuronidase and preventing hydrolysis of their glucuronides. 1,4-GL and its precursors, such as potassium hydrogen D-glucarate and calcium D-glucarate, may exert their anticancer action, in part, through alterations in steroidogenesis accompanied by changes in the hormonal environment and the proliferative status of the target organ. Thus, GA derivatives may be useful as new or adjuvant cancer preventive and therapeutic agents. In our study, 1,4-GL was found to be formed from the D-glucarate salt in the stomach of rats. It was apparently absorbed from the gastrointestinal tract, transported with the blood to different internal organs, and excreted in the urine and to a lesser extent in bile. There were no significant differences in the metabolism of PHG between male and female rats. Thus, formation of 1,4-GL from D-glucaric acid derivatives may be prerequisite for their inhibition of chemical carcinogenesis in rodents and prevention of breast, prostate, and colon cancer in humans.
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PMID:Metabolism, uptake, and excretion of a D-glucaric acid salt and its potential use in cancer prevention. 910 Oct 79

The natural bile salt taurolithocholate (TLC) impairs the biliary excretion of lipids and proteins, which are known to reach the canaliculus via vesicles. In this study we examined whether these observations could be extended to the exocytic discharge of lysosomal contents into bile. The single intravenous injection of a cholestatic dose of TLC, 3 micromol/100 g body wt., markedly inhibited the biliary excretion of the lysosomal enzymes acid phosphatase and beta-glucuronidase, despite the excretion of bile salts being normalized after a transient diminution. Under such a condition, TLC did not affect the normal transport to and the processing in lysosomes of the exogenously administered [14C]sucrose-labeled horseradish peroxidase. However, the biliary excretion of the radioactive lysosomal metabolites of the protein was significantly reduced. The results indicate that TLC can inhibit the biliary discharge of lysosomes in the rat without altering the functional integrity of these organelles. Possible explanations for these findings are discussed.
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PMID:Taurolithocholate can inhibit the biliary discharge of lysosomes in the rat. 910 9

Two soybean cDNA clones, SPK-3 and SPK-4, encoding putative protein kinases were isolated and characterized. Both cDNAs encoded approximately 40-kDa serine/threonine kinases with unusual stretches of acidic amino acids in their carboxy-terminal regions, which are highly homologous to PKABA1 from wheat and ASKs from Arabidopsis. These kinases are encoded by one- or two-copy genes in the soybean genome. Notably, SPK-3 and -4 showed different patterns of expression in various soybean tissues. SPK-3 is highly expressed in dividing and elongating tissues of young seedlings but relatively weakly in tissues of mature plants. In contrast, SPK-4 showed relatively high and constitutive expression in all the tissues examined except for leaf tissues of mature plants. Although various stressors, such as dehydration and high salinity, increased the expression of both genes, the induction kinetics were different. The two genes also differed in their response to abscisic acid (ABA). SPK-3 was induced but SPK-4 was not affected by exogenously supplied abscisic acid. In accordance with these expression data analysis of the activity of a chimeric SPK-3 promoter::beta-glucuronidase (GUS) reporter gene by transient expression in tobacco leaves confirmed the inducibility of SPK-3 by salt and ABA. Polyclonal antibodies raised against a recombinant SPK-4 protein produced in Escherichia coli specifically recognized both recombinant SPK-3 and -4 proteins. Kinase assays using affinity-purified SPK-4/ antibody complexes with crude soybean extracts as substrate identified specific phosphorylation of two 41 and 170 kDa soybean proteins that were phosphorylated on serine residues. Taken together, our results suggest that SPK-3, and/or SPK-4 are functional serine protein kinase(s). Furthermore, SPK-3 and -4 may play different roles in the transduction of various environmental stresses.
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PMID:Differential expression of two functional serine/threonine protein kinases from soybean that have an unusual acidic domain at the carboxy terminus. 926 31

A cDNA, ERD1, isolated from one-hour-dehydrated plants of Arabidopsis thaliana L. encodes a putative protein that is similar to the regulatory ATPase subunit (ClpA) of the Clp protease and contains a putative chloroplast-targeting transit-peptide at the N-terminus. A chimeric gene with the putative plastid-targeting sequence of the erd1 gene fused to the synthetic green-fluorescent protein (sGFP) gene was constructed and introduced into Arabidopsis protoplasts. The N-terminal region of the ERD1 protein directed the sGFP protein into the plastids of the protoplasts, and functioned as a transit peptide. Northern blot analysis indicated that expression of the erd1 gene was induced not only by water stress, such as dehydration and high salinity, but also by natural senescence and dark-induced etiolation. The erd1 gene was not strongly induced by exogenous abscisic acid. A chimeric gene with the 0.9 kb promoter region of the erd1 gene fused to the beta-glucuronidase (GUS) reporter gene was constructed, and tobacco plants transformed with the construct. The GUS reporter gene driven by the erd1 promoter was induced by dehydration and high salt stress at significant levels in the transgenic plants. The GUS gene was strongly expressed in older leaves without dehydration, and was induced by dark-induced etiolation. Furthermore, GUS activity was reduced by cytokinin treatment during dark-induced etiolation. These results indicate that expression of the erd1 gene is developmentally up-regulated by senescence as well as by water stress.
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PMID:A nuclear gene, erd1, encoding a chloroplast-targeted Clp protease regulatory subunit homolog is not only induced by water stress but also developmentally up-regulated during senescence in Arabidopsis thaliana. 937 97

In order to understand the molecular mechanisms which are responsible for desiccation tolerance in the resurrection plant Craterostigma plantagineum Hochst. a thorough analysis of the CDeT11-24 gene family was performed. CDeT11-24 comprises a small gene family whose genes are expressed in response to dehydration, salt stress and abscisic acid (ABA) treatment in leaves. The gene products are constitutively expressed in roots and disappear only when the plants are transferred to water. It is therefore suggested that the proteins are involved in sensing water status. The predicted proteins are very hydrophilic; they share some features with late-embryogenesis-abundant proteins, and sequence similarities were found with two ABA- and drought-regulated Arabidopsis genes. The analysis of beta-glucuronidase reporter genes driven by the CDeT11-24 promoter showed high activity in mature seeds in both transgenic Arabidopsis and tobacco. In vegetative tissues the promoter activity in response to ABA was restricted to young Arabidosis seedlings. The responsiveness to ABA during later developmental stages was regained in the presence of the Arabidopsis gene product ABI3. Dehydration-induced promoter activity was only observed in Arabidopsis leaves at a particular developmental stage. This analysis indicates that some components in the signal transduction pathway of the resurrection plant are not active in tobacco or Arabidopsis.
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PMID:Gene structure and expression analysis of the drought- and abscisic acid-responsive CDeT11-24 gene family from the resurrection plant Craterostigma plantagineum Hochst. 968 69

Glucuronide prodrugs of 9-aminocamptothecin were synthesized. Prodrug 4, in which 9-aminocamptothecin was connected to glucuronic acid by an aromatic spacer via a carbamate linkage, was stable in both aqueous solution and human plasma. Prodrug 4 and its potassium salt 12 were 20-80-fold less toxic than 9-aminocamptothecin to human tumor cell lines. The simultaneous addition of beta-glucuronidase and 4 or 12 to tumor cells resulted in a cytotoxic effect equal to that of 9-aminocamptothecin alone. Prodrugs 4 and 12 were over 80 and 4000 times more soluble than 9-aminocamptothecin in aqueous solutions at pH 4.0, respectively. Compounds 4 and 12 may be useful for prodrug monotherapy of tumors that accumulate extracellular lysosomal beta-glucuronidase as well as for antibody-directed enzyme prodrug therapy (ADEPT) of cancer.
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PMID:Design and synthesis of water-soluble glucuronide derivatives of camptothecin for cancer prodrug monotherapy and antibody-directed enzyme prodrug therapy (ADEPT). 1047 93

The use of lactobacilli as starter organisms in food fermentation processes requires thorough knowledge of their reaction to the multitude of ecological factors including their response to stress. We have characterised the dnaK gene region of Lactobacillus sakei LTH681. Two chromosomal EcoRI fragments of 2.5 and 4.0 kb were identified using a homologous dnaK probe generated by PCR. The sequence analysis of the cloned fragments showed that the dnaK gene region consists of four heat shock genes with the organisation hrcA-grpE-dnaK-dnaJ. Comparison of the deduced amino acid sequences revealed high similarity to the corresponding heat shock proteins of Gram-positive bacteria. An upstream located orfY was found which exhibited substantial similarity (41.5%) to the chloramphenicol acetyltransferase of Enterobacter aerogenes. Northern hybridisation analysis revealed that the transcription of the genes is induced by heat shock (42 degrees C) as well as salt (6%) or ethanol (10%) stress. Several transcripts were detected including a polycistronic mRNA of 4.9 kb which represents the transcript of the complete dnaK gene region indicating a tetracistronic organisation of the dnaK operon. The other RNA fragments were identified as shorter transcripts (3.7 and 1.3 kb) or cleavage products of the polycistronic mRNAs. The transcription start sites of the dnaK operon were determined under inducing and non-inducing conditions. The site varied with the applied stress condition. A regulatory CIRCE element was identified located between the transcription and translation start site. The promoter region including CIRCE was transcriptionally fused to the beta-glucuronidase reporter gene gusA and expressed in L. sakei LTH681. The kinetics of transcriptional induction of gusA by heat shocking were identical to those of the dnaK operon confirming the involvement of the CIRCE element in regulation of gene expression.
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PMID:Molecular characterisation of the dnaK operon of Lactobacillus sakei LTH681. 1055 84

In plants, a cis-acting element, DRE/CRT, is involved in ABA-independent gene expression in response to dehydration and low-temperature stress. To understand signal transduction pathways from perception of the dehydration stress signal to gene expression, we characterized a gene family for DRE/CRT-binding proteins DREB2A and DREB2B in Arabidopsis thaliana. Northern analysis showed that both genes are induced by dehydration and high-salt stress. Organ-specific northern analysis with gene-specific probes showed that these genes are strongly induced in roots by high-salt stress and in stems and roots by dehydration stress. The DREB2A gene is located on chromosome 5, and DREB2B on chromosome 3. We screened an Arabidopsis genomic DNA library with cDNA fragments of DREB2A and DREB2B as probes, and isolated DNA fragments that contained 5'-flanking regions of these genes. Sequence analysis showed that both genes are interrupted by a single intron at identical positions in their leader sequence. Several conserved sequences were found in the promoter regions of both genes. The beta-glucuronidase (GUS) reporter gene driven by the DREB2 promoters was induced by dehydration and high-salt stress in transgenic Arabidopsis plants.
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PMID:Organization and expression of two Arabidopsis DREB2 genes encoding DRE-binding proteins involved in dehydration- and high-salinity-responsive gene expression. 1080 11


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