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Query: UNIPROT:P06889 (Mol)
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The dominant +1 frameshift suppressors sufA6, sufB1 and sufB2, in Salmonella typhimurium act at runs of C and affect tRNA(Pro)1, tRNA(Pro)2 and tRNA(Pro)2, respectively. A recessive +1 frameshift suppressor, sufC, has a similar suppressor specificity (Riddle, D.L., and Roth, J.R., Mol. Biol. 66, 483 and 495, 1972). We show that sufC strains harbour two frameshift suppressors of which one, sufX201, is allelic to sufB. We cloned the sufB+ wild type allele and by recombination in vivo the mutations sufB1, sufB2 and sufX201. Determination of the DNA sequence revealed that the sufB1 and sufB2 mutations result in an extra G in the anticodon loop of the minor tRNA(Pro)2. The sufX201 mutation results in a base substitution (G43 to A43) in the anticodon stem of this tRNA. Although the sufB1 and sufB2 mutations were earlier shown to be dominant, the sufB+ wild type allele on multi copy plasmid inhibited the chromosomal sufB1, sufB2 and sufX201 mediated frameshift suppression but not that mediated by the dominant sufA6 mutation. These results are discussed in view of the possible coding specificity of these mutated tRNAs. The DNA sequence showed a potential consensus promoter sequence upstream of the structural gene for tRNA(Pro)2 and downstream a dyad symmetrical structure followed by a T cluster, a possible rho-independent termination signal. The Salmonella tRNA(Pro)2 gene is identical to the Escherichia coli counterpart reported by Komine, Y. et al. (J. Mol. Biol. 212, 579-598, 1990). While the 5' flanking sequence similarity between the two species is about 83%, the similarity of the 3' flanking sequence is only 42%. Still, the Salmonella tRNA(Pro)2 gene has a rho-independent transcriptional termination signal similar to the one present in E. coli tRNA(Pro)2 gene.
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PMID:Insertion (sufB) in the anticodon loop or base substitution (sufC) in the anticodon stem of tRNA(Pro)2 from Salmonella typhimurium induces suppression of frameshift mutations. 163 Sep 16

The present studies were performed using primary monolayer cultures of bovine glomerulosa cells to determine whether the elevation in cytosolic calcium concentration produced by angiotensin II was accompanied by an elevation in mitochondrial calcium. Exchangeable mitochondria calcium content was assessed indirectly by measuring the changes in cytosolic calcium concentration and calcium efflux produced by the mitochondrial uncoupler, carbonyl cyanide m-chlorophenylhydrazone (CCCP). Total mitochondrial calcium content was also assessed directly by atomic absorption spectroscopy. CCCP had a direct effect to promote calcium release from an oligomycin/antimycin-sensitive (mitochondrial) calcium pool in permeabilized cells. In intact cells, CCCP caused rapid reductions in cellular ATP content and the ratio of ATP to ADP. Still, its effects on calcium dynamics were exerted primarily at the mitochondrial level as evidenced by inhibition with ruthenium red, but not dantrolene. As expected, angiotensin II produced a rapid increase in calcium efflux and an equally rapid and sustained increase in cytosolic calcium concentration. Nonetheless, CCCP-stimulated elevations in cytosolic calcium concentration and calcium efflux were reduced by angiotensin II in a concentration-dependent manner. Total mitochondrial calcium content was also lower in angiotensin-treated than in control cells. These results indicate that angiotensin II causes a net decrease in mitochondrial calcium stores. On the basis of these data, it is proposed that alterations in calcium metabolism initiated by angiotensin II are exerted not only at the membrane and cytosolic levels but also at the level of the mitochondria. Changes in mitochondrial calcium dynamics may directly contribute to the regulation of mitochondrial steroidogenic enzymes by angiotensin II.
Mol Cell Endocrinol 1990 Dec 03
PMID:Evidence that angiotensin II decreases mitochondrial calcium in the glomerulosa cell. 170 33

DNase I footprinting experiments showed that binding activities of Sp1 and of GHF-1 to its distal site on the human growth hormone gene promoter are mutually exclusive. The kinetics of GHF-1 binding were indicative of positive cooperativity. The Sp1 site did not affect promoter activity in cell-free transcription. Still, Sp1 could compensate partially for the decreased stimulation of transcription seen at low GHF-1 concentrations.
Mol Cell Biol 1990 Apr
PMID:Sp1 can displace GHF-1 from its distal binding site and stimulate transcription from the growth hormone gene promoter. 218 Dec 88

Transport of palmitate from the albumin-palmitate complex in the plasma to inside mitochondria where it undergoes beta-oxidation is a multistep process. Albumin's large size prevents permeation via interendothelial clefts. Palmitate dissociation from albumin in solution is too slow to provide an adequate supply of the unbound palmitate. The discovery that the dissociation occurs upon albumin binding to an endothelial surface receptor resolves the conundrum. Palmitate transport across the luminal surface membrane may be either carrier-mediated or passive. Fatty-acid binding protein inside endothelial and cardiac muscle cells facilitates diffusion through cytosol while maintaining the unbound palmitate concentration at a very low level. Within the interstitium, albumin is again the palmitate carrier. Still controversial is whether or not there is a saturable sarcolemmal transporter or simply passive exchange. Inside the myocyte palmitate is again bound to the fatty acid binding protein which buffers the free palmitate concentration, facilitates diffusion, and may facilitate further intracellular reactions.
Mol Cell Biochem
PMID:Modeling of palmitate transport in the heart. 267 67

During its folding, the polypeptide chain of the beta 2 subunit of Escherichia coli tryptophan synthase (L-serine hydrolyase (adding indole) EC 4.2.1.20) undergoes dimerization. To decide whether this dimerization precedes or follows the formation of the native, functional, tertiary structure of the polypeptide chain, the kinetics of renaturation of beta 2 are studied by monitoring both the regain of native conformation and the dimerization. Dimer formation is followed by the increase of the fluorescence polarization, or by energy transfer between a fluorescence donor and a fluorescence acceptor, which occur upon association of adequately labelled beta chains. Renaturation is followed by the regain of functional properties of beta 2, i.e. its ability to bind pyridoxal-5'-phosphate or to form a fluorescent ternary complex with this coenzyme and L-serine. It is shown that for beta 2 the dimerization obeys first-order kinetics, presumably because it occurs rapidly after a rate-limiting isomerization of the monomer. The dimerization is followed by another isomerization, taking place within the dimer, which leads to the formation of the pyridoxal-5'-phosphate binding site. Still another, slow, isomerization reaction involving the F1 (N-terminal) domain completes the renaturation. With a modified form of beta 2 (trypsin-nicked beta 2) where this isomerization of F1 can be made to occur before the dimerization, the dimer is also shown to appear before the functional properties. It is concluded that a non-native dimer indeed exists as an obligatory intermediate on the folding pathway of nicked beta 2 and of beta 2, and that interdomain interactions are needed to force the polypeptide chains into their native conformations.
J Mol Biol 1985 Apr 20
PMID:Kinetics and importance of the dimerization step in the folding pathway of the beta 2 subunit of Escherichia coli tryptophan synthase. 389 16

Chronic treatment of neuroblastoma X glioma NG108-15 hybrid cells with the opiate agonist etorphine resulted in a decrease in both opiate receptor density (receptor down-regulation) and opiate ability to inhibit prostaglandin E1 (PGE1)-stimulated increases in cyclic AMP levels (receptor desensitization). Opiate receptor down-regulation and desensitization were homologous as indicated by the lack of apparent change in muscarinic, alpha 2-adrenergic, and PGE1 receptor binding and also retention, albeit modulation, of the ability of carbachol and norepinephrine to inhibit PGE1-stimulated increases in cyclic AMP levels after 24 hr of etorphine treatment. PGE1-stimulated increases in cyclic AMP levels remained identical in etorphine-treated and control cells. Several lines of evidence indicate that receptor desensitization and receptor down-regulation in NG108-15 cells are two separate cellular adaptation processes. (a) With an agonist which appears to be efficiently coupled, i.e., an agonist whose apparent Kd value is much larger than its apparent IC50 value for regulation of cyclic AMP levels (Ki), the concentration of ligand required to produce half-maximal down-regulation is analogous to its Ki value, whereas the concentration of ligand required to produce half-maximal desensitization is related to its Kd value; (b) receptor desensitization precedes receptor down-regulation; (c) only opiate agonists could produce receptor down-regulation, whereas both opiate agonists and partial agonists could desensitize post-receptor occupancy events. Still further evidence for dissociability of these processes was obtained by incubating NG108-15 cells with etorphine at 30 degrees for 2 hr. Under these conditions, there was a decrease in etorphine's ability to regulate adenylate cyclase while [3H]diprenorphine binding remained unaltered. IC50 values of D-Ala2-D-Leu5-enkephalin's competition for [3H]diprenorphine binding to intact cells increased 19.6-fold after etorphine treatment for 90 min, while naloxone IC50 values remained unaltered. This apparent increase in IC50 values was much lower, about 2-fold, when receptor binding was carried out in membranes isolated from cells treated with etorphine chronically. Furthermore, analysis of [3H]etorphine binding to such membranes in the presence of 10 mM Mg2+ indicated a loss of receptor binding sites with no change in apparent affinity, whereas [3H]diprenorphine binding revealed no significant alteration in either Bmax or Kd values. Therefore, during opiate receptor desensitization, a reduction of agonist high-affinity site occurs with no apparent alteration in total receptor number.
Mol Pharmacol 1983 Nov
PMID:Opiate receptor down-regulation and desensitization in neuroblastoma X glioma NG108-15 hybrid cells are two separate cellular adaptation processes. 631 14

The genomes of three main biovars of Yersinia pestis were subjected to restriction fragment length polymorphism analysis using I-CeuI endonuclease. I-CeuI which is encoded by a mobile intron in Chlamydomonas engamenans recognizes a 25-bp site in the ribosomal RNA rrl gene and cuts DNA of most representatives of Enterobacteriaceae into seven fragments corresponding to the presence of seven rrn-operons. Glycerol-positive Y. pestis strains (biovars antiqua and mediaevalis) contain seven ribosomal operons which can be recognized by I-CeuI endonuclease. However, glycerol-negative strains of Y. pestis biovar orientalis expose only six restriction sites for I-CeuI. The restriction fragment length polymorphism patterns obtained with I-CeuI make it possible to distinguish between three biovars of Y. pestis. Use of another rare cutting restriction enzyme, Bln/I, permits differentiation between pigment-adsorbing and avirulent non-pigment-adsorbing Y. pestis. Still, due to homologous recombination between the two copies of IS 100 insertion sequence bracketing the pgm-locus, the mechanism of deletions in the pgm-locus seems to be confined only to strains of biovars antiqua and mediaevalis, and can be different in Y. pestis strains of biovar orientalis. The I-CeuI restriction patterns of two Yersinia strains isolated within a ten-year period in the port of St. Petersburg and originally identified as Y. pseudotuberculosis 01 turned out to be related to typical representatives of Y. pestis biovar antiqua. These strains could be exported from the same source or circulate among Rattus norvegicus population of the port as non-pigment-adsorbing avirulent immunogenic clone.
Mol Gen Mikrobiol Virusol
PMID:The established Yersinia pestis biovars are characterized by typical patterns of I-CeuI restriction fragment length polymorphism. 747 35

The proto-oncogenes c-jun, junB, junD, and c-fos recently have been shown to encode for transcription factors with a leucine zipper that mediates dimerization to constitute active transcription factors; juns were shown to dimerize with each other and with c-fos, whereas fos was shown to dimerize only with juns. After birth, hematopoietic cells of the myeloid lineage, and some other terminally differentiated cell types, express high levels of c-fos. Still, the role of fos/jun transcription factors in normal myelopoiesis or in leukemogenesis has not been established. Recently, c-jun, junB, and junD were identified as myeloid differentiation primary response genes stably expressed following induction of terminal differentiation of myeloblastic leukemia M1 cells. Intriguingly, c-fos, though induced during normal myelopoiesis, was not induced upon M1 differentiation. To gain further insights into the role of fos/jun in normal myelopoiesis and leukemogenicity, M1fos and M1junB cell lines, which constitutively express c-fos and junB, respectively, were established. It was shown that enforced expression of c-fos, and to a lesser extent junB, in M1 cells results in both an increased propensity to differentiate and a reduction in the aggressiveness of the M1 leukemic phenotype. M1fos cells constitutively expressed immediate-early and late genetic markers of differentiated M1 cells. The in vitro differentiation of normal myeloblasts into mature macrophages and granulocytes, as well as the increased propensity of M1fos leukemic myeloblasts to be induced for terminal differentiation, was dramatically impaired with use of c-fos antisense oligomers in the culture media. Taken together, these observations show that the proto-oncogenes which encode for fos/jun transcription factors play important roles in promoting myeloid differentiation. The ability of the M1 leukemic myeloblasts to be induced for terminal differentiation in the absence of apparent fos expression indicates that there is some redundancy among the fos/jun family of transcription factors in promoting myeloid differentiation; however, juns alone cannot completely compensate for the lack of fos. Thus, genetic lesions affecting fos/jun expression may play a role in the development of "preleukemic" myelodysplastic syndromes and their further progression to leukemias.
Mol Cell Biol 1993 Feb
PMID:Proto-oncogenes of the fos/jun family of transcription factors are positive regulators of myeloid differentiation. 842 6

The immune state of insects is defined by a set of proteins that is absent in the naive state. To explore the immune system of Trichoplusia ni in more detail we have employed a PCR differential display technique to compare the mRNA population of untreated last instar larvae to that of immunized animals. In the primary display, more than one hundred bands seemed induced upon bacterial challenge. When they were used as probes in Northern blots, 35% of these probes detected inducible mRNA species. Such probes were used to screen a cDNA library from immunized larvae. We isolated clones for T. ni homologs of cecropin A, lysozyme and attacin. One differentially expressed band hybridized to clones for BJHSP1, a hemacy-anin-related protein which is hormonally up-regulated in last instar larvae; this induction is probably not related to the bacterial infection. Still other probes recognized inducible mRNAs of 1.6 and 1.0 kb. The corresponding cDNA clones did not show strong sequence homology to any known proteins. We have demonstrated the potential of this PCR technique to display both known and unknown genes specific for the immune state of whole insects against a background of genes involved in larval development.
Insect Biochem Mol Biol 1996 Feb
PMID:PCR differential display of immune gene expression in Trichoplusia ni. 888 60

Maturation of tRNA and rRNA and the assembly of the ribosome in all organisms occurs in vivo in a complex pathway in which various proteins such as endo- and exonucleases, tRNA and rRNA modifying enzymes and ribosomal proteins, act concomitantly and temporarily during the maturation process. One class of RNA binding proteins are the tRNA modifying enzymes, which catalyse the formation of various modified nucleosides present in tRNA. Here we analyse the consequences of various alterations in a tRNA on the formation of modified nucleosides in the tRNA and the aminoacylation of it under true in vivo conditions, i.e. in a cell with normal amounts of the tRNA substrate and the tRNA binding protein. We have devised a selection method to obtain mutants of tRNA(Pro)GGG in Salmonella typhimurium that may no longer be a substrate inl vivo for the tRNA(m1G37)methyltransferase. These mutant tRNAs were purified from cells in balanced growth by a solid phase hybridisation technique and the presence of 1-methylguanosine (m1G) in position 37 next to the anticodon was monitored. Of 13 different mutant tRNA(Pro)GGG species analysed, eight of them had a drastically reduced level of m1G. Some of these mutant tRNA species had alterations far from the nucleotide G37 modified by the enzyme; e.g. base-pair disruptions in the first, fourth and eighth (last) base-pair of the acceptor stem, in the D-stem, and in the top of the anticodon stem. The structure of all the mutant tRNA(Pro)GGG species must deviate from the wild-type form, since they all induced +1 frameshifting. Still, tRNA(Pro)GGG from five of the mutants had normal levels of m1G. Thus, only a subset of mutations, all inducing an altered tRNA structure, resulted in m1G deficiency. However, those alterations in tRNA(Pro)GGG, which influenced the tRNA(m1G37)methyltransferase activity, did not affect in vivo the formation of four other modified nucleosides and the aminoacylation of tRNA(Pro)GGG, demonstrating the extreme dependence of the tRNA(m1G37)methyltransferase on an almost perfect three-dimensional structure of the tRNA. We discuss that the conformation of the anticodon loop may be a major determining element for the formation of m1G37 in vivo.
J Mol Biol 1997 Feb 21
PMID:Structural requirements for the formation of 1-methylguanosine in vivo in tRNA(Pro)GGG of Salmonella typhimurium. 904 63


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