Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The primary structure of tRNAVal2a from baker's yeast has been determined. The general methods of the investigation are presented. Twenty six distinguished points can be noted in the tRNAVal2a and tRNA1Val from baker's yeast. The anticodon region of tRNAVal2a is represented by the sequence NAC, where N corresponds to a uridine analogue nucleoside of unknown structure. The comparison of primary structures of tRNAVal2a, tRNAVal2a, tRNA1Val from E. coli and tRNAVal2a and tRNA1Val from baker's yeast is analysed.
Mol Biol (Mosk)
PMID:[The primary structure of tRNA Val 2a from baker's yeast]. 121 73

The NAC (nitrogen assimilation control) protein from Klebsiella aerogenes is a LysR-like regulator for transcription of several operons involved in nitrogen metabolism, and couples the transcription of these sigma 70-dependent operons to regulation by the sigma 54-dependent NTR system. NAC activates expression of operons (e.g. histidine utilization, hut), allowing use of poor nitrogen sources, and represses expression of operons (e.g. glutamate dehydrogenase, gdh) allowing assimilation of the preferred nitrogen source, ammonium. NAC is both necessary and sufficient to activate transcription, but the expression of the nac gene is totally dependent on the central nitrogen regulatory system (NTR) and RNA polymerase carrying the sigma 54 sigma factor (RNAP sigma 54). Nitrogen starvation signals the NTR system to transcribe nac, and NAC activates the transcription of hut, put (proline utilization), and urease. NAC does not affect the transcription of RNAP sigma 54-dependent operons like ginA or nifLA, which respond directly to the NTR system, but activates transcription of RNAP sigma 70-dependent operons. Thus NAC acts as a bridge between RNAP sigma 70-dependent operons like hut and the RNAP sigma 54-dependent NTR system. The activation of operons like hut by NAC in response to nitrogen starvation is at least superficially similar to their activation by CAP-cAMP in response to carbon and energy starvation.
Mol Microbiol 1991 Nov
PMID:The role of the NAC protein in the nitrogen regulation of Klebsiella aerogenes. 166 20

The beta-lyase-dependent bioactivation of S-conjugates of tetrafluoroethylene by subcellular fractions from rat liver and rat kidney was studied. Incubation of both hepatic and renal cytosol with S-(1,2,2,2-tetrafluoroethyl)-l-cysteine (TFE-Cys) resulted in the formation of previously unidentified difluorothionamides, indicating difluorothionoacyl fluoride as the main reactive intermediate derived from the beta-lyase-dependent bioactivation of TFE-Cys. The presence of N-difluorothionoacetyl-S-(1,1,2,2-tetrafluoroethyl)-l-cystei ne (TFE-PMS) and difluoroacetic acid in urine of rats treated with N-acetyl-S-(1,1,2,2-tetrafluoroethyl)-l-cysteine (TFE-NAC) points to a similar mechanism of bioactivation in vivo. When TFE-NAC was incubated with 11,000 X g supernatants of rat kidney and liver in the absence of exogenous acetyl coenzyme A (acetyl-CoA), N-deacetylation and subsequent beta-lyase-dependent activation to difluorothionoacyl fluoride could be observed. Both the N-deacetylation of TFE-NAC and the beta-lyase-dependent activation of TFE-Cys were much faster in rat kidney then in rat liver. When TFE-Cys was incubated with 11,000 X g supernatants of rat kidney and rat liver, formation of TFE-NAC could only be observed in the presence of 2 mM exogenous acetyl-CoA; the initial rate of N-acetylation was 5-fold higher in renal then in hepatic fractions. Under these conditions, formation of TFE-PMS was very low. The low urinary excretion of unchanged TFE-NAC (3-5% of dose) upon administration of TFE-NAC points to a high N-deacetylation/N-acetylation ratio in vivo. Due to a very high turn-over of TFE-NAC/TFE-Cys, the availability of the cofactor for N-acetylation, acetyl-CoA, might be rate limiting in the kidney, resulting in accumulation of TFE-Cys followed by increasing beta-lyase-dependent bioactivation of TFE-Cys to reactive intermediates.
Mol Pharmacol 1989 Oct
PMID:Bioactivation of the cysteine-S-conjugate and mercapturic acid of tetrafluoroethylene to acylating reactive intermediates in the rat: dependence of activation and deactivation activities on acetyl coenzyme A availability. 281 61

TNF alpha and IL-1 each can activate NF-kappa B and induce gene expression of manganese superoxide dismutase (MnSOD), a mitochondrial matrix enzyme which can provide critical protection against hyperoxic lung injury. The regulation of MnSOD gene expression is not well understood. Since redox status can modulate NF-kappa B and potential kappa B site(s) exist in the MnSOD promoter, the effect of thiols (including NAC, DTT and 2-ME) on TNF alpha and IL-1 induced activation of NF-kappa B and MnSOD gene expression was investigated. Activation of NF-kB and increased MnSOD expression were potentiated by thiol reducing agents. In contrast, thiol oxidizing or alkylating agents inhibited both NF-kappa B activation and elevated MnSOD expression in response to TNF alpha or IL-1. Since protease inhibitors TPCK and TLCK can inhibit NF-kappa activation, we also investigated the effect of these compounds on MnSOD expression and NF-kappa B activation. TPCK and TLCK each inhibited MnSOD gene expression and NF-kappa B activation. Since the MnSOD promoter also contains an AP-1 binding site, the effect of thiols and thiol modifying agents on AP-1 activation was investigated. Thiols had no consistent effect on AP-1 activation. Likewise, some of the thiol modifying compounds inhibited AP-1 activation by TNF alpha or IL-1, whereas others did not. Since diverse agents had similar effects on activation of NF-kappa B and MnSOD gene expression, we have demonstrated that activation of NF-kappa B and MnSOD gene expression are closely associated and that reduced sulfhydryl groups are required for cytokine mediation of both processes.
Mol Cell Biochem 1995 Jul 05
PMID:Thiol modulation of TNF alpha and IL-1 induced MnSOD gene expression and activation of NF-kappa B. 747 33

Synthesis of urease by Klebsiella species is known to be induced when the nitrogen source of the growth medium is limiting, suggesting that urease gene expression is controlled by the nitrogen regulatory (ntr) system. This study showed that K. pneumoniae with mutations in either ntrA or ntrC, two integral components of the ntr system, were phenotypically urease-negative. These mutants could be complemented back to a urease positive phenotype with recombinant plasmids encoding the corresponding ntr gene. A series of ure-lacZYA transcriptional fusions, in conjunction with primer extension analysis, identified a DNA region that encoded a nitrogen-regulated promoter. This promoter region controlled transcription of ureD, the first gene in the Klebsiella pneumoniae urease gene cluster, and ureA, a gene that resides immediately downstream of ureD. A high level of transcription from the ureD promoter required NAC, a recently characterized member of the nitrogen regulatory cascade. NAC is a Lys R-like transcriptional regulator that can act at sigma 70 promoters; expression from nac itself is dependent upon NTRA. Therefore, expression of K. pneumoniae urease was dependent upon the nitrogen regulatory cascade, and transcription of at least two urease genes was from a promoter that was positively regulated by NAC.
Mol Microbiol 1993 Apr
PMID:Identification of a nitrogen-regulated promoter controlling expression of Klebsiella pneumoniae urease genes. 849 92

We report the characterization of clone 1.9.2, a gene expressed in mineralizing osteoblasts. Remarkably, clone 1.9.2 is the murine homolog of the alpha chain of the nascent polypeptide-associated complex (alpha-NAC). Based on sequence similarities between alpha-NAC/1.9.2 and transcriptional regulatory proteins and the fact that the heterodimerization partner of alpha-NAC was identified as the transcription factor BTF3b (B. Wiedmann, H. Sakai, T. A. Davis, and M. Wiedmann, Nature 370:434-440, 1994), we investigated a putative role for alpha-NAC/ 1.9.2 in transcriptional control. The alpha-NAC/1.9.2 protein potentiated by 10-fold the activity of the chimeric activator GAL4/VP-16 in vivo. The potentiation was shown to be mediated at the level of gene transcription, because alpha-NAC/1.9.2 increased GAL4/VP-16-mediated mRNA synthesis without affecting the half-life of the GAL4/VP-16 fusion protein. Moreover, the interaction of alpha-NAC/1.9.2 with a transcriptionally defective mutant of GAL4/VP-16 was severely compromised. Specific protein-protein interactions between alpha-NAC/1.9.2 and GAL4/VP-16 were demonstrated by gel retardation, affinity chromatography, and protein blotting assays, while interactions with TATA box-binding protein (TBP) were detected by immunoprecipitation, affinity chromatography, and protein blotting assays. Based on these interactions that define the coactivator class of proteins, we conclude that the alapha-NAC/1.9.2 gene product functions as a transcriptional coactivator.
Mol Cell Biol 1998 Mar
PMID:The alpha chain of the nascent polypeptide-associated complex functions as a transcriptional coactivator. 948 45

The alpha chain of the nascent polypeptide-associated complex (alpha-NAC) coactivator was shown to potentiate the activity of the homodimeric c-Jun activator, while transcription mediated by the c-Fos/c-Jun heterodimer was unaffected. The use of deletion mutants in pull-down assays revealed that alpha-NAC interacted with amino acids 1 to 89 of the c-Jun protein and that the coactivator could interact with both the unphosphorylated and the serine 73-phosphorylated form of c-Jun. N-terminal-deleted c-Jun protein failed to interact with alpha-NAC in mammalian two-hybrid assays, while mutant c-Jun proteins lacking the leucine zipper or the basic domain retained interaction with alpha-NAC in vivo. Kinetics studies with purified c-Jun homodimer and recombinant alpha-NAC proteins allowed determination of the mechanism of coactivation by alpha-NAC: the coactivator stabilized the AP-1 complex formed by the c-Jun homodimer on its DNA recognition sequence through an eightfold reduction in the dissociation constant (kd) of the complex. This effect of alpha-NAC was specific, because alpha-NAC could not stabilize the interactions of JunB or Sp1 with their cognate binding sites. Interestingly, the expression of alpha-NAC was first detected at 14.5 to 15 days postconception, concomitantly with the onset of ossification during embryogenesis. The alpha-NAC protein was specifically expressed in differentiated osteoblasts at the centers of ossification. Thus, the alpha-NAC gene product exhibits the properties of a developmentally regulated, bone-specific transcriptional coactivator.
Mol Cell Biol 1998 Mar
PMID:Bone-specific expression of the alpha chain of the nascent polypeptide-associated complex, a coactivator potentiating c-Jun-mediated transcription. 948 46

When cybrids with a point mutation, which locates in the tRNALeu(UUR) gene of mtDNA and causes a mitochondrial encephalomyopathy (MELAS syndrome), were exposed to a high concentration of oxygen (95%), the peroxide production markedly increased by 6 h of oxygen exposure, whereas the peroxide production was similar among the cybrids under a normal concentration of oxygen. The peroxide production by oxygen exposure was enhanced particularly in cybrids with high proportions of the mutant mtDNA and low respiratory capacities. The appearance of apoptotic cells by oxygen exposure was high in cybrids with the impaired respiratory function due to the mutation. An antioxidant NAC successfully suppressed both the peroxide production and apoptosis. These results imply that the peroxide production plays an important role in inducing apoptosis in cells carrying the mtDNA mutation causing encephalomyopathy.
Biochem Mol Biol Int 1998 Sep
PMID:Peroxide production and apoptosis in cultured cells carrying mtDNA mutation causing encephalomyopathy. 978 41

Activation of the CYP1A1 gene has been described to be mediated by the cytosolic Ah receptor (AhR) and a possible cooperative role of the 4S benzo(a)pyrene-binding protein (4S protein). Carbaryl (CAR) has been shown to induce human CYP1A1 gene expression without binding to the human AhR. In this study, Sprague-Dawley rats received a single i.p. dose of 20, 80, 150 micromol/kg CAR or NAPn (naphthalene, the aromatic part of CAR) and were sacrificed after 24 h. CAR increased ethoxyresorufin-O-deethylase and methoxyresorufin-O-demethylase activities, the level of CYP1A1, 1A2 proteins, and CYP1A1 mRNA at the highest dose, whereas NAPn showed no effects. Moreover, CAR, naphthol (its major metabolite) and NAPn were not ligands in vitro of the TCDD binding site of AhR or the benzo(a)-pyrene binding site of 4S protein in rat, neither was CAR a ligand of these two binding sites in mice, dog, monkey or human. Molecular properties of CAR were evaluated and showed that this molecule is far from the structural characteristics of CYP 1A1 specific inducers although a planar conformation can be achieved with an energy < 5 kJ x mol(-1). The data demonstrated that CAR could also modulate the AhR-mediated responses, even though it did not meet the structural requirements to be ligand of AhR.
Int J Mol Med 1998 Nov
PMID:Effects of carbaryl and naphthalene on rat hepatic CYP1A1/2: potential binding to Ah receptor and 4S benzo(a)pyrene-binding protein. 985 62

Geminiviruses encode a few proteins and depend on cellular factors to complete their replicative cycle. As a way to understand geminivirus-host interactions, we have searched for cellular proteins which interact with viral proteins. By using the yeast two-hybrid technology and the wheat dwarf geminivirus (WDV) RepA protein as a bait, we have isolated a family of proteins which we termed GRAB (for Geminivirus Rep A-binding). We report here the molecular characterization of two members, GRAB1 and GRAB2. We have found that the 37 C-terminal amino acids of RepA are required for interaction with GRAB proteins. This region contains residues conserved in an equivalent region of the RepA proteins encoded by other viruses of the WDV subgroup. The N-terminal domain of GRAB proteins is necessary and sufficient to interact with WDV RepA. GRAB proteins contain an unique acidic C-terminal domain while their N-terminal domain, of ca. 170 amino acids, are highly conserved in all of them. Interestingly, this conserved N-terminal domain of GRAB proteins exhibits a significant amino acid homology to the NAC domain present in proteins involved in plant development and senescence. GRAB1 and GRAB2 mRNAs are present in cultured cells and roots but are barely detectable in leaves. GRAB expression inhibits WDV DNA replication in cultured wheat cells. Our studies highlight the importance that the pathway(s) mediated by GRAB proteins, as well as by other NAC domain-containing proteins, might have on geminivirus DNA replication in connection to plant growth, development and senescence pathways.
Plant Mol Biol 1999 Mar
PMID:GRAB proteins, novel members of the NAC domain family, isolated by their interaction with a geminivirus protein. 1035 80


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