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:1.2.1.13 (glyceraldehyde-3-phosphate dehydrogenase)
6,511 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tryptophanyl-tRNA synthetase (TrpRS) exists in two forms in human cells, i.e., a major form which represents the full-length protein and a truncated form (mini TrpRS) in which an NH(2)-terminal extension is deleted because of alternative splicing of its pre-mRNA. Mini TrpRS can act as an angiostatic factor, while full-length TrpRS is inactive. We herein show that an oxidized form of human glyceraldehyde-3-phosphate dehydrogenase (GapDH) interacts with both full-length and mini TrpRSs and specifically stimulates the aminoacylation potential of mini, but not full-length, TrpRS. In contrast, reduced GapDH did not bind to TrpRSs and did not influence their aminoacylation activity. Mutagenesis experiments clarified that the NH(2)-terminal Rossmann fold region of GapDH is crucial for its interaction with mini TrpRS as well as tRNA and for the regulation of its aminoacylation potential and suggested that monomeric GapDH can bind to mini TrpRS and stimulate its aminoacylation activity. These results suggest that the angiostatic human mini, but not the full-length, TrpRS may play an important role in the intracellular regulation of protein synthesis under conditions of oxidative stress.
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PMID:Oxidative stress-responsive intracellular regulation specific for the angiostatic form of human tryptophanyl-tRNA synthetase. 1562 63

Selenophosphate, an activated form of selenium that can serve as a selenium donor, is generated by the selD gene product, selenophosphate synthetase (SPS). Selenophosphate is required by several bacteria and by mammals for the specific synthesis of Secys-tRNA, the precursor of selenocysteine in selenoenzymes. Although free selenide can be used in vitro for synthesis of selenophosphate, the physiological system that donates selenium to SPS is incompletely characterized. To detect potential selenium-delivery proteins, two known sulfurtransferases and glyceraldehyde-3-phosphate dehydrogenase (GAPDH; EC 1.2.1.12) were analyzed for ability to bind and transfer selenium. Rhodanese (EC 2.8.1.1) was shown to bind selenium tightly, with only part of the selenium being available as substrate for SPS in the presence of added reductant. 3-Mercaptopyruvate sulfurtransferase (3-MST; EC 2.8.1.2) and GAPDH also bound selenium supplied as selenodiglutathione formed from SeO3(2-) and glutathione. Selenium bound to 3-MST and GAPDH was released more readily than that from rhodanese and also was more available as a substrate for SPS. Although rhodanese retained tightly bound selenium under aerobic conditions, the protein gradually became insoluble, whereas GAPDH containing bound selenium was stable at neutral pH for a long period. These results indicate that 3-MST and GAPDH have more suitable potentials as a physiological selenium-delivery protein than rhodanese. In the presence of a selenium-binding protein, a low level of selenodiglutathione formed from SeO3(2-) and glutathione could effectively replace the high concentrations of selenide routinely used as substrate in the SPS in vitro assays.
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PMID:Characterization of potential selenium-binding proteins in the selenophosphate synthetase system. 1565 70

Poly-tRNA theory have revealed that the tRNA gene-clusters in the Bacillus subtilis trrnD- and rrnB-operons are relics of early peptide-synthesizing RNA apparatus. The trrnD-type and rrnB-type poly-tRNA models were re-analyzed by using recent databases. The results elucidated that the 16 amino acid (aa)-trrnD- and the 21 aa-rrnB-peptides (whose aa sequences are in the order of aa specificities of tRNAs in the respective tRNA cluster) are really relics of earliest peptides encoded by most primitive mRNAs, trrnD-mRNA and rrnB-mRNA, which are homologous to tRNA(Gly) and tRNA(His), respectively. Genes encoding various protein superfamilies (including pgtB protein, glycyl-tRNA synthetase alpha, C-type lectin, F1-ATP-synthase gamma, etc) were concluded to have derived from tRNA(Gly)-tRNA(Cys)-tRNA(Leu) region (including trrnD-mRNA region) in the trrnD-poly-tRNA. Genes for another group of protein superfamilies (including adenylate kinase, glyceraldehyde-3-phosphate dehydrogenase, helix-turn-helix DNA-binding domains, etc.) were found to have derived rrnB-mRNA, which is most plausibly homologous to a region containing the tRNA(His) of the rrnB-poly-tRNA. Thus Proto-tRNA((Gly)) reconstructed from tRNA(Gly) and other tRNAs strongly suggested that proto-tRNA was most plausibly a viroid-like possibly self-cleavable replicable ribozyme possessing a possible hammerhead-like structure.
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PMID:Evolution from possible primitive tRNA-viroids to early poly-tRNA-derived mRNAs: a new approach from the poly-tRNA theory. 1690 Oct 93

Tumour-specific chromosomal rearrangements are known to create chimaeric products with the ability to generate many human cancers. hTAF(II)68-TEC (where hTAF(II)68 is human TATA-binding protein-associated factor II 68 and TEC is translocated in extraskeletal chondrosarcoma) is such a fusion product, resulting from a t(9;17) chromosomal translocation found in extraskeletal myxoid chondrosarcomas, where the hTAF(II)68 NTD (N-terminal domain) is fused to TEC protein. To identify proteins that control hTAF(II)68-TEC function, we used affinity chromatography on immobilized hTAF(II)68 (NTD) and MALDI-TOF (matrix-assisted laser-desorption ionization-time-of-flight) MS and isolated a novel hTAF(II)68-TEC-interacting protein, GAPDH (glyceraldehyde-3-phosphate dehydrogenase). GAPDH is a glycolytic enzyme that is also involved in the early steps of apoptosis, nuclear tRNA export, DNA replication, DNA repair and transcription. hTAF(II)68-TEC and GAPDH were co-immunoprecipitated from cell extracts, and glutathione S-transferase pull-down assays revealed that the C-terminus of hTAF(II)68 (NTD) was required for interaction with GAPDH. In addition, three independent regions of GAPDH (amino acids 1-66, 67-160 and 160-248) were involved in binding to hTAF(II)68 (NTD). hTAF(II)68-TEC-dependent transcription was enhanced by GAPDH, but not by a GAPDH mutant defective in hTAF(II)68-TEC binding. Moreover, a fusion of GAPDH with the GAL4 DNA-binding domain increased the promoter activity of a reporter containing GAL4 DNA-binding sites, demonstrating the presence of a transactivation domain(s) in GAPDH. The results of the present study suggest that the transactivation potential of the hTAF(II)68-TEC oncogene product is positively modulated by GAPDH.
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PMID:Regulation of oncogenic transcription factor hTAF(II)68-TEC activity by human glyceraldehyde-3-phosphate dehydrogenase (GAPDH). 1730 60

Opinions on the systematic relationships of birds in the avian order Gruiformes have been as diverse as the families included within it. Despite ongoing debate over monophyly of the order and relationships among its various members, recent opinion has converged on the monophyly of a "core" group of five families classified as the suborder Grues: the rails (Rallidae), the cranes (Gruidae), the Limpkin (Aramidae), the trumpeters (Psophiidae), and the finfoots (Heliornithidae). We present DNA sequence data from four mitochondrial (cytochrome b, 12S rRNA, Valine tRNA, and 16S rRNA) and three nuclear loci (intron 7 of beta-fibrinogen, intron 5 of alcohol dehydrogenase-I, and introns 3 through 5 of glyceraldehyde-3-phosphate dehydrogenase) to test previous hypotheses of interfamilial relationships within Grues, with particular attention to the enigmatic family Heliornithidae. Separate and combined analyses of these gene sequences confirm the monophyly of Grues as a whole, and of the five families individually, including all three species of Heliornithidae. The preferred topology unambiguously supports relationships among four of the five families, with only the position of Psophiidae remaining equivocal. Bayesian "relaxed-clock" dating methods suggest that the divergences of the three heliornithid species occurred in the mid-Tertiary, suggesting that their present disjunct pantropical distribution is a result of early- to mid-Tertiary dispersal.
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PMID:Phylogeny of "core Gruiformes" (Aves: Grues) and resolution of the Limpkin-Sungrebe problem. 1741 74

There is evidence that the binding of deprenyl, a monoamine oxidase (MAO) B inhibitor, and other propargylamines to glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is primarily responsible for their neuroprotective and antiapoptotic effects. Thus, GAPDH may be a target for other neuroprotective drugs. Using two independent approaches, radioligand analysis and an optical biosensor technique, we demonstrate here that GAPDH also interacts with the endogenous, reversible MAO B inhibitor, isatin. Deprenyl inhibited both [3H]isatin binding to GAPDH, and the binding of this enzyme to an isatin analogue, 5-aminoisatin, immobilized on to an optical biosensor cell. Another MAO inhibitor, tranylcypromine, was ineffective. Both deprenyl and isatin inhibited GAPDH-mediated cleavage of E. coli tRNA, and their effects were not additive. We suggest that isatin may be an endogenous partial functional agonist of deprenyl in its effect on GAPDH and GAPDH-mediated RNA cleavage. Changes in level of endogenous isatin may influence the neuroprotective effect of deprenyl in vivo.
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PMID:Isatin interaction with glyceraldehyde-3-phosphate dehydrogenase, a putative target of neuroprotective drugs: partial agonism with deprenyl. 1744 20

Monoclonal antibody (Mab) 8B7 was shown in a previous study to inhibit protein translation in lysates of Sf21 cells. The antibody was thought to be specific for a 60-kDa form of elongation factor-1 alpha (EF-1alpha), primarily because the antigen immunoprecipitated by Mab 8B7 cross-reacted with Mab CBP-KK1, an antibody generated to EF-1alpha from Trypanosoma brucei. The purpose of the current study was to investigate further the antigenic specificity of Mab 8B7. The concentration of the 60-kDa antigen relative to total cellular protein proved insufficient for its definitive identification. However, subcellular fractionation of Sf21 cells yielded an additional protein of 37 kDa in the cytosolic and microsomal fractions that was reactive with Mab 8B7. The 37-kDa protein could be easily visualized by colloidal Coomassie Blue G-250 staining as a series of pI 6.9-8.4 spots on two-dimensional gels. Excision of an abundant immunoreactive spot enabled identification of the protein as glyceraldehyde-3-phosphate dehydrogenase (GAPDH) by matrix-assisted laser desorption/ionization-mass spectrometry (MALDI-MS) and protein database searching. Subsequent immunoblotting of purified rabbit skeletal muscle GAPDH with Mab 8B7 confirmed the antibody's specificity for GAPDH. Besides the pivotal role GAPDH plays in glycolysis, the enzyme has a number of noncanonical functions, including binding to mRNA and tRNA. The ability of Mab 8B7 to disrupt these lesser-known functions of GAPDH may account for the antibody's inhibitory effect on in vitro translation.
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PMID:A monoclonal antibody that inhibits translation in Sf21 cell lysates is specific for glyceraldehyde-3-phosphate dehydrogenase. 1885 May 93

Onconase is a cytotoxic ribonuclease which targets tumor cells in vivo and in vitro. To date, cellular tRNA appeared to be the major target for Onconase mediated cytotoxic activity. Most recently we demonstrated that Onconase can also cleave double-stranded RNA (dsRNA). Incubation of Onconase at 37 degrees C with GAPDH gene-dsRNA (approximately 440 bp long) and dsRNA ladder showed degradation of dsRNA into a spectrum of smaller dsRNA fragments. Moreover, incubation of dsRNA substrates at 40 degrees C under similar conditions markedly potentiated further cleavage of dsRNAs. The recently discovered double-stranded RNase activity of Onconase suggests another mechanism for inducing cell death/apoptosis in malignant phenotypes via the RNA interference mechanism involving siRNA and miRNA.
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PMID:Effect of Onconase on double-stranded RNA in vitro. 1941 47

Functionally related genes are coregulated by specific RNA-protein interactions that direct transcript-selective translational control. In myeloid cells, interferon (IFN)-gamma induces formation of the heterotetrameric, IFN-gamma-activated inhibitor of translation (GAIT) complex comprising glutamyl-prolyl tRNA synthetase (EPRS), NS1-associated protein 1 (NSAP1), ribosomal protein L13a and glyceraldehyde-3-phosphate dehydrogenase (GAPDH). This complex binds defined 3' untranslated region elements within a family of inflammatory mRNAs and suppresses their translation. IFN-gamma-dependent phosphorylation, and consequent release of EPRS and L13a from the tRNA multisynthetase complex and 60S ribosomal subunit, respectively, regulates GAIT complex assembly. EPRS recognizes and binds target mRNAs, NSAP1 negatively regulates RNA binding, and L13a inhibits translation initiation by binding eukaryotic initiation factor 4G. Repression of a post-transcriptional regulon by the GAIT system might contribute to the resolution of chronic inflammation.
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PMID:The GAIT system: a gatekeeper of inflammatory gene expression. 1953 51

Glutamyl-prolyl tRNA synthetase (EPRS) is a component of the heterotetrameric gamma-interferon-activated inhibitor of translation (GAIT) complex that binds 3'UTR GAIT elements in multiple interferon-gamma (IFN-gamma)-inducible mRNAs and suppresses their translation. Here, we elucidate the specific EPRS phosphorylation events that regulate GAIT-mediated gene silencing. IFN-gamma induces sequential phosphorylation of Ser(886) and Ser(999) in the noncatalytic linker connecting the synthetase cores. Phosphorylation of both sites is essential for EPRS release from the parent tRNA multisynthetase complex. Ser(886) phosphorylation is required for the interaction of NSAP1, which blocks EPRS binding to target mRNAs. The same phosphorylation event induces subsequent binding of ribosomal protein L13a and GAPDH and restores mRNA binding. Finally, Ser(999) phosphorylation directs the formation of a functional GAIT complex that binds initiation factor eIF4G and represses translation. Thus, two-site phosphorylation provides structural and functional pliability to EPRS and choreographs the repertoire of activities that regulates inflammatory gene expression.
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PMID:Two-site phosphorylation of EPRS coordinates multimodal regulation of noncanonical translational control activity. 1964 14


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