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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An accelerated rate of glucose transport and catabolism is a common characteristic of cellular transformation. We have previously found elevated expression of the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) in human pancreatic and colonic adenocarcinomas (Schek et al.: Cancer Res 48:6354-6359, 1988). To investigate further the expression of this enzyme in the process of tumorigenesis, we examined GAPDH expression in a panel of oncogene-transformed fibroblasts. Significant elevations of GAPDH mRNA and glucose transporter protein mRNA levels were observed in ras- and mos-transformed NIH 3T3 cells, whereas little or no change was found in c-src-, v-src-, c-myc-, E1A-, v-fos-, and PKC-gamma-transfected cells. Furthermore, the level of GAPDH mRNA correlated with the transformed state in a series of ras-transformed and revertant cell lines. Immunoblot analysis confirmed that GAPDH polypeptide was significantly elevated in the cell lines with elevated mRNA levels. Cell cycle analysis data suggested that the effect on GAPDH expression correlated with oncogene expression rather than cell growth fraction. These results suggest that altered GAPDH gene expression occurs during some growth deregulated states, and this, along with increased glucose transporter (and possibly other glycolytic enzyme) expression, is likely to contribute to the increased metabolic capacity of cells in these states.
Mol Carcinog 1989
PMID:Increased expression of glycolysis-associated genes in oncogene-transformed and growth-accelerated states. 276 28

A nuclear gene encoding cytosolic glyceraldehyde-3-phosphate dehydrogenase from maize (subunit GAPC1, gene Gpc1) and 2.2 x 10(3) base-pairs of its 5' flanking region have been cloned and sequenced. The structure of the maize Gpc1 gene (10 introns) is different from that of the maize gene encoding subunit GAPA of chloroplast glyceraldehyde-3-phosphate dehydrogenase (1 intron) and relatively similar to that of the chicken gene (11 introns). Introns in the Gpc1 gene show a positional polarity; the more 3' their position, the more they are displaced relative to introns in the chicken gene. The Gpc1 gene and other nuclear genes from maize are associated with CpG islands, the relative size of which determines the degree of codon bias in the gene. The promoter of the maize Gpc1 gene contains an anaerobic regulatory element and a pyrimidine box upstream from the TATA box and within intron 1. Southern blotting analyses and Northern hybridizations suggest that there are three functional Gpc genes in maize whose transcript levels are controlled differentially by anaerobiosis. In spite of its "typical" anaerobic promoter, the Gpc1 gene does not seem to be an anaerobic gene in vivo.
J Mol Biol 1989 Aug 20
PMID:Structure, evolution and anaerobic regulation of a nuclear gene encoding cytosolic glyceraldehyde-3-phosphate dehydrogenase from maize. 281 Mar 56

Isolation and characterization of the chicken erythroid anion transporter (band 3) cDNA clone, pCHB3-1, revealed that the chicken erythroid band 3 polypeptide is 844 amino acids in length with a predicted mass of 109,000 daltons. This polypeptide is composed of a hydrophilic N-terminal cytoplasmic domain and a hydrophobic C-terminal transmembrane domain. The approximately 90 N-terminal amino acids of the human and murine erythroid band 3 polypeptides are absent in the predicted sequence of the chicken erythroid band 3 polypeptide. The absence of this very acidic N-terminal region is consistent with the lack of binding of glyceraldehyde-3-phosphate dehydrogenase to chicken erythroid band 3, as well as the relatively basic isoelectric point observed for this molecule. The remainder of the cytoplasmic domain shows little similarity to the cytoplasmic domain of the murine and human erythroid band 3, with the exception of the putative ankyrin-binding site, which is highly conserved. In contrast, the transmembrane domain of the chicken band 3 polypeptide is very similar to that of the murine erythroid and human nonerythroid band 3 polypeptides. The transmembrane domain contains 10 hydrophobic regions that could potentially traverse the membrane 12 to 14 times. In addition, a variant of chicken erythroid band 3, pCHB3-2, was cloned in which one of the hydrophobic regions of pCHB3-1 is lacking. The transcript complementary to pCHB3-2 accumulated in chicken erythroid cells in a similar manner as the transcript complementary to pCHB3-1 during embryonic development. This is the first example of a transporter protein or ion channel with alternative primary structures in its membrane-spanning segments.
Mol Cell Biol 1988 Mar
PMID:Alternative primary structures in the transmembrane domain of the chicken erythroid anion transporter. 283 70

A method for a 50-60-fold purification of a cysteine proteinase from trophozoites of Entamoeba histolytica using 35-80% ammonium sulphate fractionation, gel chromatography on Sephadex G-75, and preparative isoelectric focusing is described. The enzyme was examined for its proteolytic potencies towards native enzyme substrates. The amebic proteinase directly inactivates aldolase and glyceraldehyde-3-phosphate dehydrogenase from rabbit muscle as well as glucose-6-phosphate dehydrogenase from yeast. The inactivation of citrate synthase from porcine heart proceeds rather slowly, whereas malate dehydrogenase from porcine heart is not affected by the amebic proteinase under the condition used. With the exception of aldolase all inactivated enzyme substrates have been cleaved by limited proteolyses yielding major cleavage products. The inactivation of aldolase probably functions by the release of a small segment from a terminus being essential for aldolase activity.
Mol Biochem Parasitol 1986 Jan
PMID:Cysteine proteinase of Entamoeba histolytica. I. Partial purification and action on different enzymes. 287 Apr 30

Renal tubular lesions induced in male rats by two different carcinogens, N-nitrosomorpholine (NNM) and N-ethyl-N-hydroxyethylnitrosamine (EHEN), using a limited exposure "stop" protocol were investigated histochemically to demonstrate phenotypic cellular changes. The parameters measured included basophilia, glycogen content and the activity of the enzymes glucose-6-phosphatase (G6PASE), glycogen synthetase (SYN), glycogen phosphorylase (PHO), glucose-6-phosphate dehydrogenase (G6PDH), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), succinate dehydrogenase (SDH), alkaline phosphatase (ALP), acid phosphatase (ACP) and gamma-glutamyl transpeptidase (gamma-GT). The lesions observed were predominantly of either basophilic or oncocytic types. In each case, tubular lesions (altered tubules) appeared to give rise to epithelial tumors (epitheliomas) with the same cellular phenotype. Basophilic tubules and epitheliomas proved to be strongly positive for GAPDH and G6PDH while demonstrating a reduction or loss of G6PASE, ALP, ACP, gamma-GT, and SDH compared with controls and the surrounding proximal or distal tubules. In addition, large basophilic epitheliomas demonstrated an increase in both SYN and PHO activities. In contrast, most oncocytic tubules and oncocytomas characterized by abundant densely granular cytoplasm showed a reduction in the activity of G6PDH, but were intensely positive for SDH. However, a few oncocytic lesions demonstrated a decrease in both SDH and G6PDH activity. Rarely, decreased SDH and elevated G6PDH activities were observed in altered tubules resembling oncocytic tubules. It remains to be clarified whether these tubules represent a variation of the oncocytic lesions or, perhaps, another type of tubular lesion. The results indicate that basophilic and oncocytic epithelial tumors differ in their cytochemical pattern and histogenesis. In line with earlier suggestions, the basophilic tumors apparently originate from the proximal renal tubules, while the oncocytomas develop from the distal parts of the nephron. The basophilic tumors are characterized by an increased pentose phosphate pathway and glycolysis, with a corresponding reduction in mitochondrial respiration. However, the majority of the oncocytomas show an increased activity of the mitochondrial enzyme SDH, and a marked decrease in the activity of the key enzyme of the pentose phosphate pathway.
Virchows Arch B Cell Pathol Incl Mol Pathol 1986
PMID:Correlative histochemical studies on preneoplastic and neoplastic lesions in the kidney of rats treated with nitrosamines. 287 45

During influenza virus infection, protein synthesis is maintained at high levels and a dramatic switch from cellular to viral protein synthesis occurs despite the presence of high levels of functional cellular mRNAs in the cytoplasm of infected cells (M. G. Katze and R. M. Krug, Mol. Cell. Biol. 4:2198-2206, 1984). To determine the step at which the block in cellular mRNA translation occurs, we compared the polysome association of several representative cellular mRNAs (actin, glyceraldehyde-3-phosphate dehydrogenase, and pHe7 mRNAs) in infected and uninfected HeLa cells. We showed that most of these cellular mRNAs remained polysome associated after influenza viral infection, indicating that the elongation of the proteins encoded by these cellular mRNAs was severely inhibited. Because the polysomes containing these cellular mRNAs did not increase in size but either remained the same size or decreased in size, the initiation step in cellular protein synthesis must also have been defective. Several control experiments established that the cellular mRNAs sedimenting in the polysome region of sucrose gradients were in fact associated with polyribosomes. Most definitively, puromycin treatment of infected cells caused the dissociation of polysomes and the release of cellular, as well as viral, mRNAs from the polysomes, indicating that the cellular mRNAs were associated with polysomes that were capable of forming at least a single peptide bond. A similar analysis was performed with HeLa cells infected by adenovirus, which also dramatically shuts down cellular protein synthesis. Again, it was found that most of the cellular mRNAs, which were translatable in reticulocyte extracts, remained associated with polysomes and that there was a combined initiation-elongation block to cellular protein synthesis. In cells infected by both adenovirus and influenza virus, influenza viral mRNAs were on larger polysomes than were several late adenoviral mRNAs with comparably sized coding regions. In addition, after influenza virus superinfection of cells infected by the adenovirus mutant dl331, a situation in which there is a limitation in the amount of functional initiation factor eIF-2 (M. G. Katze, B. M. Detjen, B. Safer, and R. M. Krug, Mol. Cell. Biol. 6:1741-1750, 1986), influenza viral mRNAs, but not late adenoviral mRNAs, were on polysomes. These results indicate that influenza viral mRNAs are better initiators of translation than are late adenoviral mRNAs.
 ...
PMID:Cellular mRNA translation is blocked at both initiation and elongation after infection by influenza virus or adenovirus. 302 55

We have developed a simple cell-free system for studying the stability of different mRNAs in vitro. We demonstrate that the threefold greater stability in vivo of truncated c-myc mRNA (lacking exon 1) compared with that of full-length c-myc mRNA is maintained in our in vitro system. Chimeric mRNAs in which the first exon of c-myc was fused to immunoglobulin C alpha heavy chain or glyceraldehyde-3-phosphate dehydrogenase mRNAs were not rapidly degraded, demonstrating that c-myc exon 1 alone is not sufficient to tag mRNAs for rapid degradation. Competition experiments show that full-length c-myc mRNA is specifically recognized by a factor(s) responsible for its rapid degradation. This system will allow further characterization and purification of these factors.
Mol Cell Biol 1988 Jul
PMID:Differential stability of c-myc mRNAS in a cell-free system. 313 24

Drosophila melanogaster contains two genes encoding glyceraldehyde-3-phosphate dehydrogenase, Gapdh-1 and Gapdh-2. The two genes are highly conserved in their coding sequences but not in their noncoding and flanking sequences. We report that both genes are expressed at higher levels in larval, late pupal, and adult stages than in embryonic, early, and midpupal stages. However, a major difference in the expression of the two genes is observed in the adult stage, during which the level of the Gapdh-1 transcript decreases over fourfold, while that of the Gapdh-2 transcript remains at a constant high level. In addition, the Gapdh-1 transcript appears highly enriched in the thorax section compared with the head and abdomen sections, while the Gapdh-2 transcript is evenly distributed. Analyses of the expression patterns of the two Gapdh hybrid genes, GAP1/2 and GAP2/1, revealed that the two genes have a distinct organization of their regulatory sequences. The principle regulatory sequences of Gapdh-2 reside upstream of the translation start, while the principle sequences specifying the level and developmental pattern of Gapdh-1 expression reside downstream of the translation start.
Mol Cell Biol 1988 Dec
PMID:Differential regulation of the two glyceraldehyde-3-phosphate dehydrogenase genes during Drosophila development. 314 11

The structure of apo-glyceraldehyde-3-phosphate dehydrogenase (GAPDHase) from Bacillus stearothermophilus has been refined using a restrained least-squares method. The final crystallographic R-factor is 0.177 for all 53,315 reflections between 7.0 and 2.5 A. The resulting model has been analysed with respect to lattice interactions, molecular symmetry, temperature factors and solvent structure showing that, apart from local deviations due to intermolecular contact, the molecule exhibits a very high degree of local 222 symmetry. Analysis of differences between the structure of apo-GAPDHase and the previously refined holo-GAPDHase at 1.8 A resolution reveals details of conformational change in the enzyme induced by cofactor binding. The change, which was previously described as a rigid-body rotation of the coenzyme-binding domain with respect to the catalytic domain, is of more complex nature and involves relative shifts of several structural elements in the coenzyme-binding domain and some small changes in the catalytic domain. A possible mechanism of this conformational change is proposed based on the comparison of the refined structures and model-building studies. According to this mechanism, the adenosine moiety of NAD can initially bind to the protein in the apo-enzyme conformation. Several attractive interactions resulting from the initial binding of the coenzyme trigger conformational changes in the molecule of GAPDHase that: (1) create the productive nicotinamide-moiety binding site; (2) improve enzyme-coenzyme interactions at the adenosine moiety; (3) modify the active site to optimize the positioning of catalytic residues and ion-binding sites. Implications of the proposed mechanism for existing experimental data on binding of NAD analogues to GAPDHase are discussed.
J Mol Biol 1988 Oct 20
PMID:Coenzyme-induced conformational changes in glyceraldehyde-3-phosphate dehydrogenase from Bacillus stearothermophilus. 321 Feb 37

The intracellular concentrations of the polypeptides encoded by the two enolase (ENO1 and ENO2) and three glyceraldehyde-3-phosphate dehydrogenase (TDH1, TDH2, and TDH3) genes were coordinately reduced more than 20-fold in a Saccharomyces cerevisiae strain carrying the gcr1-1 mutation. The steady-state concentration of glyceraldehyde-3-phosphate dehydrogenase mRNA was shown to be approximately 50-fold reduced in the mutant strain. Overexpression of enolase and glyceraldehyde-3-phosphate dehydrogenase in strains carrying multiple copies of either ENO1 or TDH3 was reduced more than 50-fold in strains carrying the gcr1-1 mutation. These results demonstrated that the GCR1 gene encodes a trans-acting factor which is required for efficient and coordinate expression of these glycolytic gene families. The GCR1 gene and the gcr1-1 mutant allele were cloned and sequenced. GCR1 encodes a predicted 844-amino-acid polypeptide; the gcr1-1 allele contains a 1-base-pair insertion mutation at codon 304. A null mutant carrying a deletion of 90% of the GCR1 coding sequence and a URA3 gene insertion was constructed by gene replacement. The phenotype of a strain carrying this null mutation was identical to that of the gcr1-1 mutant strain.
Mol Cell Biol 1987 Feb
PMID:The GCR1 gene encodes a positive transcriptional regulator of the enolase and glyceraldehyde-3-phosphate dehydrogenase gene families in Saccharomyces cerevisiae. 354 83


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