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Query: UNIPROT:P06889 (Mol)
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A novel gene product, GPR74, with homology to the seven transmembrane-domain receptor superfamily, has been cloned. GPR74 has been identified from the expressed sequence tags (EST) database. Subsequent PCR amplification of that sequence and screening of a human heart cDNA library led to the isolation of a 1.7-kb cDNA clone encoding a protein of 408 amino acids. GPR74 shows highest amino acid identity (33%) to the human neuropeptide Y-receptor subtype Y2. The human and mouse genes for GPR74 have been isolated and their exon-intron structures determined. In both species the gene consists of four exons spanning around 20 kb with the exon-intron borders being 100% conserved. Northern analysis of various human tissues reveals highest levels of mRNA expression in brain and heart. In situ hybridisation analysis of rat brain tissue confirms this result and identifies the hippocampus and amygdala nuclei as the brain areas with particular high expression of GPR74 mRNA. Fluorescence in situ hybridisation, PCR analysis on a radiation hybrid panel and interspecific mouse backcross mapping have localised the genes to human chromosome 4q21 and mouse chromosome 5. Expression of the human GPR74 cDNA as a GFP-fusion protein in various cell lines reveals the inability of the recombinant receptor protein to reach the cell surface. This is consistent with the lack of NPY specific binding in these cells and suggests that unknown factors are required for a full functional receptor complex.
Brain Res Mol Brain Res 2000 May 05
PMID:Molecular cloning and characterisation of GPR74 a novel G-protein coupled receptor closest related to the Y-receptor family. 1083 15

The application of expressed sequence tag (EST) technology has proven to be an effective tool for gene discovery and the generation of gene expression profiles. The generation of an EST resource for the cardiovascular system has revealed significant insights into the changes in gene expression that guide heart development and disease. Furthermore, an important genetic resource has been developed for cardiovascular biology that is valuable for data mining and disease gene discovery.
Mol Med Today 2000 Jun
PMID:A cardiovascular EST repertoire: progress and promise for understanding cardiovascular disease. 1084 Mar 81

We have identified a mammalian homologue of yeast Ump1p by searching for similar proteins in human and mouse expressed sequence tag (EST) databases. Ump1p is an accessory protein that is required for normal proteasome assembly in yeast (1). A mammalian homologue, which we refer to as "proteassemblin," is a constituent of proteasome assembly intermediates (preproteasomes), but not fully assembled 20S proteasomes, as is Ump1p in yeast. We also provide evidence that proteassemblin is a constituent of pre-immunoproteasomes that contain the precursor of the interferon-gamma-inducible subunit LMP2. By analogy with Ump1p, we hypothesize that proteassemblin is required for normal mammalian proteasome assembly.
Mol Cell Biol Res Commun 2000 Apr
PMID:Identification of proteassemblin, a mammalian homologue of the yeast protein, Ump1p, that is required for normal proteasome assembly. 1089 94

Since 1997 the National Center for Documentation and Evaluation of Alternative Methods to Animal Experiments, ZEBET, in Berlin, has been coordinating a validation study aimed at prevalidation and validation of three in vitro embryotoxicity tests, funded by the European Center for the Validation of Alternative Methods (ECVAM) at the Joint Research Center (JRC, Ispra, Italy). The tests use the cultivation of postimplantation rat whole embryos (WEC test), cultures of primary limb bud cells of rat embryos (micromass or, MM, test), and cultures of a pluripotent mouse embryonic stem cell line (embryonic stem cell test or EST). Each of the tests was performed in four laboratories under blind conditions. In the preliminary phase of the validation study 6 out of 20 test chemicals comprising different embryotoxic potential (non, weakly, and strongly embryotoxic) were tested. The results were used to define biostatistically based prediction models (PMs) to identify the embryotoxic potential of test chemicals for the WEC test and the MM test. The PMs developed with the results of the preliminary phase of the validation study (training set) will be evaluated with the results of the remaining 14 test chemicals (definitive phase) by the end of the study. In addition, the existing, improved PM (iPM) for the EST, which had been defined previously, was evaluated using the results of the preliminary phase of this study. Applying the iPM of the EST to the results of this study, in 79% of the experiments, chemicals were classified correctly according to the embryotoxic potential defined by in vivo testing. For the MM and the WEC test, the PMs developed during the preliminary phase of this validation study provided 81% (MM test) and 72% (WEC test) correct classifications. Because the PM of the WEC test took into account only parameters of growth and development, but not cytotoxicity data, a second PM (PM2) was developed for the WEC test by incorporating cytotoxicity data of the differentiated mouse fibroblast cell line 3T3, which was derived from the EST. This approach, which has previously never been used, resulted in an increase to 84% correct classifications in the WEC test.
In Vitr Mol Toxicol 2000
PMID:Development of prediction models for three in vitro embryotoxicity tests in an ECVAM validation study. 1090 Apr 7

Single direct partial sequencing of anonymous cDNA clones was performed to obtain genetic information on red algae Porphyra yezoensis of which genetic information is not available. This expressed sequence tags (EST) analysis revealed 81 clones (42%) had significant homologies to known genes in GenBank. Of these clones, eight are related to known algal genes, whereas above 90% of the EST clones were newly identified in algae. Putative functional categories of these clones showed that the most abundant genes were involved in stress and defense mechanisms and that the next abundant genes were associated with protein synthetic pathways.
Mol Cells 2000 Jun 30
PMID:Analysis of expressed sequence tags of Porphyra yezoensis. 1090 Nov 73

The phosphatase and tensin homology deleted on chromosome 10 (PTEN) is a tumor suppressor gene with sequence homology to tyrosine phosphatases and the cytoskeletal proteins tensin and auxilin. PTEN has recently been shown to inhibit cell migration and the spreading and formation of focal adhesions. This study investigated the role of PTEN in carcinoma invasion in a lung-cancer cell line and examined the downstream genes regulated by PTEN. We have previously established a cell-line model in human lung adenocarcinoma with different invasive abilities and metastatic potentials. Examining PTEN gene expression in these cell lines, we found that a homozygous deletion in exon 5 is associated with high invasive ability. We then constructed stable constitutive and inducible wild-type PTEN-overexpressed transfectants in the highly invasive cell line CL(1-5). We found that an overexpression of PTEN can inhibit invasion in lung cancer cells. To further explore the downstream genes regulated by PTEN, a high-density complementary DNA (cDNA) microarray technique was used to profile gene changes after PTEN overexpression. Our results indicate a panel of genes that can be modulated by PTEN. PTEN overexpression downregulated genes, including integrin alpha(6), laminin beta(3), heparin-binding epidermal growth factor-like growth factor, urokinase-type plasminogen activator, myb protein B, Akt2, and some expressed sequence tag (EST) clones. In contrast, PTEN overexpression upregulated protein phosphatase 2A1B, ubiquitin protease (unph), secreted phosphoprotein 1, leukocyte elastase inhibitor, nuclear factor-kappaB, cyclic adenosine monophosphate response element binding protein, DNA ligase 1, heat shock protein 90, and some EST genes. Northern hybridization and flow cytometry analysis also confirmed that PTEN overexpression results in the reduced expression of the integrin alpha(6) subunit. The results of this study indicate that PTEN overexpression may inhibit lung cancer invasion by downregulation of a panel of genes including integrin alpha(6). The cDNA microarray technique may be an effective tool to study the downstream function of a tumor suppressor gene.
Am J Respir Cell Mol Biol 2000 Sep
PMID:Profiling the downstream genes of tumor suppressor PTEN in lung cancer cells by complementary DNA microarray. 1097 Aug 13

To assist genetic research into Cryptomeria japonica, which is one of the most important forest tree species in Japan, expressed sequence tag (EST) analysis was carried out. The cDNA clones were isolated from a library derived from inner bark tissues. Partial sequences were obtained from 2231 clones, representing 1398 unique transcripts. Putative functions were assigned to 1583 clones, which represented 882 unique transcripts, by a Blast algorithm. Homology analysis suggested that ESTs related to cell wall formation represented about 3% of the clones. Transcripts of plant stress response genes were also abundant in the inner bark library, especially genes involved in wounding and drought responses. This indicates that the stress response systems of this tree species are similar to those of other plants, and that these systems are highly conserved among plant species. The remaining 648 clones, which represented 516 unique transcripts, did not show any significant homology to known sequences in the databases searched: these are expected to represent genes specific to Cryptomeria and, possibly, to related species.
Plant Mol Biol 2000 Jul
PMID:Expression analysis of ESts derived from the inner bark of Cryptomeria japonica. 1105 97

Laminariales (Phaeophyceae, Heterokonta) are characterised by a heteromorphic digenetic life cycle with a filamentous, microscopic gametophyte and a highly evolved, macroscopic sporophyte. With the ultimate goal of comparing gene expression in each life cycle stage, complementary DNA libraries were constructed from sporophytes and gametophytes of Laminaria digitata. A set of ca. 500 expressed sequence tags (EST) was generated from each life history phase, by single-run partial sequencing of randomly picked cDNA clones. Comparison of the EST deduced amino acid sequences with database protein sequences assigned a putative identity for 39% of the 412 gametophyte clones and 48% of the 493 sporophyte clones sequenced thus far. These data represent more than 152 different proteins now probably identified in L. digitata. Several of those newly identified proteins are of interest to our understanding of the molecular physiology of kelps, for example their carbon-concentrating mechanisms, cell wall biosynthesis and halogen metabolism. EST analysis also confirmed that genes with long 3'-UTRs are widespread in Laminariales and the study of 5'-UTRs allowed the identification of a Kozak consensus sequence, c(A/C)A(A/C)CAUGGc(G/T). Several potential developmentally regulated differences in gene expression are discussed.
Plant Mol Biol 2000 Jul
PMID:Characterisation of complementary DNAs from the expressed sequence tag analysis of life cycle stages of Laminaria digitata (Phaeophyceae). 1105 2

Estrogen sulfotransferase (EST) is the sole sulfotransferase expressed in normal human breast epithelial cells and has an important function in determining free estrogen hormone levels in these cells. In the present study we examined the inhibitory effect of the dietary polyphenols quercetin and resveratrol on EST activity, i.e. 17beta-estradiol (E2) sulfation. Both the compounds potently inhibited recombinant human EST in a competitive fashion with K(i) values of about 1 microM. In fact, both polyphenols could serve as substrates for EST. In order to extend the studies to more physiologically relevant conditions, we examined whether inhibition of EST also occurred in the intact cultured human mammary epithelial (HME) cells. The mean baseline EST activity (E2 sulfate formation) in the HME cells was 4.4 pmol/h per mg protein. The IC(50) for resveratrol was very similar to that for recombinant EST, i.e. about 1 microM. Surprisingly, quercetin was 10 times more potent in the HME cells with an IC(50) of about 0.1 microM, a concentration that should be possible to achieve from the normal dietary content of this flavonoid.
J Steroid Biochem Mol Biol
PMID:Quercetin and resveratrol potently reduce estrogen sulfotransferase activity in normal human mammary epithelial cells. 1107 Mar 55

GenBank contains 14 477 expressed sequence tags (EST) derived from mouse oocyte cDNA libraries: 3499 of these are from two unfertilized oocyte libraries and 10 978 are from two fertilized oocyte libraries. Gene expression profiles were obtained for these libraries by matching library EST to UniGene clusters. The 14 477 EST identified 4226 UNIGENES: These were screened using HomoloGene to identify 1386 homologous UniGene clusters in two other species with one of the matches being human. Within these human matches, 840 encoded named proteins, 223 encoded hypothetical proteins, and 323 encoded clustered EST. The set of named genes provides the first step in establishing a database of genes expressed in mouse oocytes and, by extension, human oocytes.
Mol Hum Reprod 2001 Jun
PMID:A set of 840 mouse oocyte genes with well-matched human homologues. 1138 8


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