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)

A pleiotropic mutation in the purB gene of E. coli is described which lowers the spontaneous mutation frequency of other genes. The antimutator effect is very large for some genetic loci, but is absent at other sites. Both forward and reverse mutations are affected. This mutation in purB is temperature sensitive for both adenine auxotrophy and the antimutator action. Adenine, or adenosine, or low temperature growth abolish the antimutator effect. The mutagenicity of base analogs and nitrosoguanidine at several loci was found to be reduced by this purB mutation. The antimutator effect is recessive in strains merodiploid for the purB region. The frequency of reversion of mutation on F' episomes is affected by the chromosomal antimutator, which therefore acts in trans. Xray and UV sensitivity are normal in this mutant, which is the first antimutator characterized in E. coli.
Mol Gen Genet 1977 May 20
PMID:A conditional antimutator in E. coli. 32 7

Molecular mechanisms of base pair substitutions induced by 2-aminopurine and 2,6-diaminopurine have been proposed by calculations of nonbonded interaction energy of this substances with nucleic acid bases. The calculation results suppose that the main pathways of the transitions are wobble pair formations of these analogues with cytosine. The possibility of the transversions as a result of incorporation of 2-aminopurine and 2,6-diaminopurine in DNA have been considered. The influence of nucleotide sequences and enzymes of nucleic acid synthesis on induced mutation frequencies have been discussed.
Mol Biol (Mosk)
PMID:[Molecular mechanisms of 2-aminopurine and 2,6-diaminopurine induced mutations]. 47 Sep 39

The previously given systems-theoretic model for the synthesis of optical antipodes (AD and AL) in strongly asymmetric yield, which shows mono-bistable behaviour depending on the degree of "openess" of the chemical reaction system is reconsidered for two equal compartments (subscripts 1 and 2 on A) with coupling by diffusion. In this configuration three threshold values, j1, is less than j2 is less than j3, for the influx j of the common precursor substance appear. For j is less than j1 only one steady state (s.s.) with no optical activity (ADi = ALi, i-1;2) and equal distribution of the antipodes in both compartments (AD1 = AD2, AL1 = AL2) exists. For j is greater than j 1, this totally symmetric s.s. becomes unstable and a pair of s.s. with optical activity (AD1 is less than AL1, AD2 is less than AL2 or AD1 is greater than AL1, AD2 is greater than AL2) but no spatial asymmetry emerges (parallel flipping), i.e. both compartments be8have as a whole, showing a preponderance of either the D- or the L-form. For j is greater than j2 in addition two new s.s. are possible with antiparallel flipping (AD1 is less than AL1, AD2 is greater than AL2 or AD1 is greater than AL1, AD2 is less than AL2), i.e. in one compartment the D-form has the majority and in the other one the L-form, but these are stable only beyond a third threshold value j3. A third thinkable pair with no optical activity, but different sum concentrations in both cells, does not exist in this special circuitry, but can be obtained in a slightly changed arrangement. So for j is greater than j2, 5 different (4 stable, 1 unstable) s.s., exist for the same set of parameters, one of which is chosen by the system.
J Mol Evol 1975 Oct 29
PMID:Five simultaneous steady states in a flipping two-compartment-system with optical antipodes. 120 30

Transcriptional activation of the murine Cyp1a-1 (cytochrome P(1)450) gene by inducers such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) (dioxin) requires the aromatic hydrocarbon (Ah) receptor and the interaction of an inducer-receptor complex with one or more of the Ah-responsive elements (AhREs) located about 1 kb upstream from the transcriptional initiation site. We find that treatment of mouse hepatoma Hepa-1 cells with 2-aminopurine, an inhibitor of protein kinase activity, inhibits CYP1A1 mRNA induction by TCDD as well as the concomitant increase in CYP1A1 enzyme activity. Formation of DNA-protein complexes between the Ah receptor and its AhRE target is also inhibited by 2-aminopurine, as determined by gel mobility shift assays. Phosphorylation is required for the formation of Ah receptor-specific complexes, since in vitro dephosphorylation of nuclear extracts from TCDD-treated Hepa-1 cells abolishes the capacity of the Ah receptor to form specific complexes with its cognate AhRE sequences. To determine whether any one of several known protein kinases was involved in the transcriptional regulation of the Cyp1a-1 gene, we treated Hepa-1 cells with nine other protein kinase inhibitors prior to induction with TCDD; nuclear extracts from these cells were analyzed for their capacity to form specific DNA-protein complexes. Only extracts from cells treated with staurosporine, a protein kinase C inhibitor, were unable to form these complexes. In addition, staurosporine completely inhibited CYP1A1 mRNA induction by TCDD. Depletion of protein kinase C by prolonged treatment with phorbol ester led to the complete suppression of CYP1A1 mRNA induction by TCDD. We conclude that (i) phosphorylation is necessary for the formation of a transcriptional complex and for transcriptional activation of the Cyp1a-1 gene; (ii) the phosphorylation site(s) exists on at least one of the proteins constituting the transcriptional complex, possibly the Ah receptor itself; and (iii) the enzyme responsible for the phosphorylation is likely to be protein kinase C.
Mol Cell Biol 1992 Apr
PMID:Dioxin-dependent activation of murine Cyp1a-1 gene transcription requires protein kinase C-dependent phosphorylation. 131 72

By the use of digitonin permeabilized presynaptic nerve terminals (synaptosomes), we have found that intrasynaptic mitochondria, when studied "in situ," i.e., surrounded by their cytosolic environment, are able to buffer calcium in a range of calcium concentrations close to those usually present in the cytosol of resting synaptosomes. Adenine nucleotides and polyamines, which are usually lost during isolation of mitochondria, greatly improve the calcium-sequestering activity of mitochondria in permeabilized synaptosomes. The hypothesis that the mitochondria contributes to calcium homeostasis at low resting cytosolic free calcium concentration ([Ca2+]i) in synaptosomes has been tested; it has been found that in fact this is the case. Intrasynaptic mitochondria actively accumulates calcium at [Ca2+]i around 10(-7) M, and this activity is necessary for the regulation of [Ca2+]i. When compared with other membrane-limited calcium pools, it was found that depending on external concentration the calcium pool mobilized from mitochondria is similar or even greater than the IP3- or caffeine-sensitive calcium pools. In summary, the results presented argue in favor of a more prominent role of mitochondria in regulating [Ca2+]i in presynaptic nerve terminals, a role that should be reconsidered for other cellular types in light of the present evidence.
Mol Biol Cell 1992 Feb
PMID:Regulation of cytosolic free calcium concentration by intrasynaptic mitochondria. 155 Sep 64

Nerve growth factor (NGF) leads to neuronal differentiation of PC12 cells and promotes their survival in serum-free medium. Past studies have shown that purine analogues block some of the effects of NGF but not others and thus that they can be used to dissect the mechanistic pathways of its action. In the present work we used 2-aminopurine (2-AP) and 6-thioguanine (6-TG) to examine whether NGF causes activation of primary response genes through a single signaling pathway or via multiple pathways. Northern blot analysis and nuclear run-off transcription assays were used to assess the activation of c-fos, c-jun, TIS1, TIS8, and TIS11 after exposure of PC12 cells to NGF in the presence or absence of 2-AP and 6-TG. Our findings indicate that NGF appears to employ at least three distinct pathways to induce early genes in PC12 cells. This suggests that the NGF signaling mechanism diverges at an early point after interaction of NGF with its receptor.
Mol Biol Cell 1992 Mar
PMID:Nerve growth factor employs multiple pathways to induce primary response genes in PC12 cells. 162 34

The bacterial transposon Tn5 inserts into dozens of sites in a gene, some of which are used preferentially (hotspots). Features of certain sites and precedents provided by several other transposons had suggested that sequences in target DNA corresponding to the ends of Tn5 or of its component IS50 elements might facilitate transposition to these sites. We tested this possibility using derivatives of plasmid pBR322 carrying IS50 I or O end sequences. Tn5 inserted frequently into an IS50 I end at the major hotspot in pBR322, but not into either an I end or an O end 230 bp away from this hotspot. Adenine (dam) methylation at GATC sequences in the I end segment interferes with its use as the end of a transposon, but a dam- mutation did not affect Tn5 insertion relative to an I end sequence in target DNA. These results support models in which the ability of Tn5 to find its preferred sites depends on several features of DNA sequence and conformation, and in which target selection is distinct from recognition of the element ends during transposition.
Mol Gen Genet 1991 Aug
PMID:Tn5 insertion specificity is not influenced by IS50 end sequences in target DNA. 165 4

The suppression of growth arrest-specific (gas) gene expression by serum appeared to be independent of protein synthesis, but expression in resting cells was sensitive to 2-aminopurine, an inhibitor of intracellular protein kinases. Although accumulation of gas gene mRNA was reduced by serum, nuclear transcription of the gas-2, -3, and -5 genes was observed in serum-stimulated cells, indicating that posttranscriptional events may regulate mRNA levels. Growth induction by serum, on the other hand, led to suppression of transcription of the gas-1 gene. Cell cycle regulation and the serum response of gas-1 were lost in ras-transformed cells.
Mol Cell Biol 1990 Apr
PMID:Regulation of expression of growth arrest-specific genes in mouse fibroblasts. 169 Aug 45

Eukaryotic viruses have devised numerous strategies to downregulate activity of the interferon-induced, double-stranded (dsRNA)-activated protein kinase (referred to as p68 on the basis of its Mr of 68,000 in human cells). Viruses must exert this control to avoid extensive phosphorylation of the alpha subunit of eukaryotic initiation factor 2 (eIF-2) by p68 and the resultant negative effects on protein synthesis initiation. To begin to define the molecular mechanisms underlying this regulation, we optimized expression of p68 in an in vitro transcription-translation system utilizing the full-length cDNA clone. The in vitro-expressed kinase was autophosphorylated in response to dsRNAs and heparin in a manner similar to that for the native p68 provided that the kinase inhibitor, 2-aminopurine, was present during the in vitro translation reaction. Further, the activated kinase efficiently phosphorylated its natural substrate, the alpha subunit of eIF-2. Binding experiments revealed that the expressed kinase complexed with the dsRNA activator, reovirus dsRNA, as well as the adenovirus-encoded inhibitor, VAI RNA. Interestingly, both the reovirus RNAs and VAI RNA also complexed with protein kinase molecules that lacked the carboxyl terminus and all catalytic domains. Deletion analysis confirmed that the p68 amino terminus contained critical determinants for reovirus dsRNA and VAI RNA binding. Further, reovirus dsRNA efficiently bound to, but failed to activate, p68 kinase molecules containing a single amino acid substitution in the invariant lysine 295 present in catalytic domain II. Taken together, these data demonstrate that this expression system permits a detailed mutagenic analysis of the regions of p68 required for interaction with virus-encoded activators and repressors.
Mol Cell Biol 1991 Nov
PMID:Functional expression and RNA binding analysis of the interferon-induced, double-stranded RNA-activated, 68,000-Mr protein kinase in a cell-free system. 171 30

To realize bioassays a primary culture method was carried out with dissociated cells from the garden snail gonads. ADN and protein syntheses of gonadal cells were estimated using the liquid scintillation method. The gonadal cells were obtained from either adults of Petits Gris and Gros Gris, or young Gros Gris. The results were remarkably homogeneous. The brain extracts added to the culture medium had an inhibitory dose dependent effect on the synthetic activity of gonadal cells. The effected bioassays permit quantitative estimation on the variations of the brain extracts effect in relation to the physiological states of the snail and on the evolution of target cells' receptors during the growth of Gros Gris.
Cell Mol Biol 1991
PMID:[Development of a bioassay from gonadal cellular cultures of the snail Helix aspersa: influence of nerve ganglion extracts on the synthetic activity of the target cells]. 177 19


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