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 method for binding tRNA to ribosomes, introduced by Watanabe [Watanabe, S. (1972) J. Mol. Biol. 67, 443-457], permits nonenzymatic binding of N-acetyl-Phe-tRNA(Phe) to either the ribosomal aminoacyl-tRNA (A) or peptidyl-tRNA (P) site with almost 100% specificity. We used this method to analyze a possible codon-anticodon interaction at the P site for NH(2)-blocked aminoacyl-tRNA and deacylated tRNA. N-Acetyl-Phe-tRNA(Phe) bound only to the P site of poly(U)-programmed 70S ribosomes, not to poly(A)-programmed ribosomes. The reverse mRNA dependence was found for N-acetyl-Lys-tRNA(Lys). A series of purified deacylated tRNAs was analyzed in the poly(U) and poly(A) system for abilities to block P-site binding of N-acetyl-aminoacyl-tRNA and to direct the N-acetyl-aminoacyl-tRNA to the A site. Only the cognate tRNA was as effective as the bulk tRNA at a concentration of less than 1/20th that of bulk tRNA. tRNAs whose corresponding codons are identical or similar (same base character) in the first two codon positions showed a low but significant effect. The other noncognate tRNAs were unable to direct the NH(2)-blocked aminoacyl-tRNAs to the A site. Chlortetracycline interfered neither with the P-site binding of NH(2)-blocked aminoacyl-tRNA nor with the effects of deacylated tRNAs. Furthermore, the translocation blocker viomycin affected neither the binding to the A site nor that to the P site. These effects of both antibiotics indicate that both kinds of tRNA do not bind transiently in the A site before filling the P site and that codon-anticodon interaction takes place at the P site.
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PMID:Codon-anticodon interaction at the ribosomal P (peptidyl-tRNA)site. 22 15

By genetic analysis we examined UV mutagenesis of the Escherichia coli glyU gene. When carried by M13 phage mp9, glyU is subject to induced UV mutagenesis which is dependent on the umuC+ and recF+ genes. When carried by M13 phage mp8, glyU is not subject to induced UV mutagenesis. This difference is correlated with the nature of the target nucleotides: CTC in the mp9 derivative and GAG in the mp8 derivative. Thus, we conclude that the induced (umuC and recF dependent) mutagenesis is locally targeted on pyrimidine cyclobutane or 6-4 dimers. glyU carried by M13 is equally subject to uninduced UV mutagenesis whether carried by mp8 or mp9. This uninduced mutagenesis is independent of the umuC+, recF+ and recA+ genes and we hypothesize that it is regionally targeted on pyrimidine cyclobutane or 6-4 dimers in the vicinity of the target CTC and GAG nucleotides. The role of recF in UV mutagenesis was tested in two ways. First, mutagenesis of glyU carried by M13 mp9 in a recA730 genetic background was found to be recF dependent. Because recA730 renders induced UV mutagenesis partially constitutive, we conclude that the RecF product plays a direct role in UV mutagenesis rather than, or in addition to, any indirect regulatory role it may play. Second, UV mutagenesis of E. coli chromosomal glyU was found to be recF independent while UV mutagenesis of M13-bourne glyU was recF dependent. We conclude that the mechanism of induced UV mutagenesis of the E. coli chromosome is at least partly different from that of M13 phage and we discuss the biochemical basis for such a difference.
Mol Gen Genet 1987 Apr
PMID:Genetic analysis of UV mutagenesis of the Escherichia coli glyU gene. 243 81

In this study we report on some lines of ongoing research performed in our laboratory, in relation to the increased expression of FcR on tumor cells, as well as on cells present in the tumor-bearing host, and its possible role in tumor progression. In a previous study we have shown that a Polyoma virus (PyV)-induced anaplastic carcinoma (SEYF-a tumor) contained an FcR-expressing subpopulation of tumorigenic cells. We tested the effect of in vivo passaging of FcR-expressing and of non-FcR-expressing sub-populations of SEYF-a tumor cells on the expression of FcR, as revealed by the ability of these cells to bind the 2.4G2 monoclonal antibody, which is directed against mouse Fc gamma 2b/gamma 1R. It was found that upon in vivo passaging these two sub-populations became practically identical in their ability to bind anti-Fc gamma R antibody. On the other hand, in vitro passaging of FcR-expressing SEYF-a cells resulted in a gradual decrease in the expression of Fc gamma R. These results, indicating that the expression of Fc gamma R on tumor cells, per se, is dependent on a factor present in the in vivo environment were confirmed using 3T3 cells transformed in vitro by PyV (C) and forming tumors at first injection to mice (CTC). C cultures of various clones did not express Fc gamma R, while CTC cultures (cultures from tumors) became positive. We also detected an increase in the level of a soluble form of Fc gamma 2b/gamma 1R in the circulation of mice bearing PyV induced tumors. This increase paralleled the appearance of palpable tumors. A similar pattern of increase was observed in mice inoculated with the c-H-ras transformed tumorigenic clone 8/F/5, but not in mice inoculated with non-tumorigenic 3T3 cells. Data published by us show that metastatic breast cancer patients had significantly elevated Fc gamma R levels on their peripheral blood mononuclear cells (PBMC). Experiments presented here indicate a direct correlation between increased Fc gamma R levels on PBMC and tumor mass in colon, ovary and lung metastatic carcinoma patients. The possibility that malignantly transformed cells have the potential to cause proliferation of Fc gamma R expressing T cells was tested. It was found that extract derived from r-H-ras transformed 3T3 cells triggers the proliferation of a T cell hybridoma expressing Fc gamma R.
Mol Immunol 1988 Nov
PMID:Increased expression of Fc gamma receptor in cancer patients and tumor bearing mice. 285 35

A 25-kb DNA region, previously cloned from Pseudomonas syringae pv. syringae 61 in cosmid pHIR11, enables nonpathogenic bacteria such as Pseudomonas fluorescens and Escherichia coli to elicit the hypersensitive response (HR) in tobacco (Nicotiana tabacum). hrmA is located within this region, adjacent to a conserved cluster of hrp genes, and is essential for nonpathogens to elicit the HR. DNA sequence analysis suggested that hrmA was the second of two genes in an operon and was preceded by an open reading frame (ORF), ORF1, which is predicted to encode a 10.9-kDa protein. DNA gel blot analysis revealed that sequences hybridizing with a DNA fragment internal to hrmA were absent from P. syringae pv. syringae B728a, P. syringae pv. tabaci 11528, and P. syringae pv. glycinea race 4 U1, but present in P. syringae pv. tomato DC3000. A 2.4-kb BamHI-AvrII fragment carrying hrmA, ORF1, and native regulatory sequences was subcloned into broad-host-range vector pDSK519 and electroporated into P. syringae pv. syringae B728a and P. syringae pv. tabaci 11528. The presence of the hrmA locus had no apparent effect on the ability of P. syringae pv. syringae B728a to cause brown spot of bean, but it caused P. syringae pv. tabaci 11528 to elicit the defense-associated HR rather than disease in N. tabacum cvs. Xanthi N and Xanthi NC and N. clevelandii. Furthermore, N. debeyii, N. glutinosa, N. rustica, and N. tabacum cvs. Petit Havana and Samsun responded with the HR to P. fluorescens(pHIR11). In contrast, N. benthamiana-P. syringae pv. tabaci interactions were unaffected by the presence of HrmA, and P. fluorescens(pHIR11) did not elicit the HR in N. benthamiana. The hrmA ORF was subcloned into pFLAG-CTC, which expressed HrmA with a C-terminal FLAG synthetic epitope fusion. Escherichia coli MC4100 cells carrying the functional hrp cluster and the hrmA-FLAG derivative secreted the HrpZ harpin, but not HrmA-FLAG, to the medium, as indicated by immunoblot analysis with M2 anti-FLAG and polyclonal anti-HrpZ antibodies. The hrmA ORF was also subcloned into plant expression vector pFF19 and then biolistically delivered, along with pFF19G (expressing beta-glucuronidase), into suspension-cultured tobacco cells. Histochemical staining 24 h later revealed substantial beta-glucuronidase activity in cells receiving pFF19G and pFF19 but not in those receiving pFF19G and pFF19-HrmA. Thus, internal production of HrmA was deleterious to tobacco cells.
Mol Plant Microbe Interact 1997 Jul
PMID:Evidence that the Pseudomonas syringae pv. syringae hrp-linked hrmA gene encodes an Avr-like protein that acts in an hrp-dependent manner within tobacco cells. 920 63

The allotype of human immunoglobulin kappa light chain constant region gene (IGKC) has been identified by the serological assay or DNA typing method. The three allotypes Km*1, Km*1,2 and Km*3 have amino acid substitutions at positions of codons 153 and 191 in the kappa light chain constant region. The Km allotypes were designated as follows: Km*1 has valine (GTC) at position 153 and leucine (CTC) at 191; Km*1,2 has Ala153 (GCC) and Leu191 (CTC); Km*3 has Ala153 (GCC) and Val191 (GTC). In this study, polymerase chain reaction-allele specific oligonucleotide (PCR-ASO) was used to provide a specific allelic typing system for the IGKC gene in 213 unrelated Koreans. For Km genotyping, the IGKC coding regions plus 35 bp of the 3' untranslated regions were amplified with specific primers. Amplified genes were hybridized with Km ASO probes at positions of codons 153 and 191 and were detected using a colorimetric detection method. The frequencies of Km*1,2/Km*1,2, Km*1,2/Km*3, and Km*3/Km*3 were 17.8% (n=38), 51.7% (n=110), and 30.5% (n=65), respectively. The estimated allele frequencies for Km*1,2 and Km*3 were 0.44 and 0.56, respectively. The homozygote or the heterozygote of Km*1 was not observed in this study. The PCR-ASO method distinguished the alleles Km*3, Km*1,2, and Km*1 and also distinguished the homozygote from heterozygote. Km frequencies vary significantly among various populations. Km*3 in Koreans was very similar to those observed in northern Chinese, Japanese, and the native people of British Columbia. It was lower than that reported in Caucasian, Indian, or southern Chinese.
Mol Cells 1997 Aug 31
PMID:Km genotyping using polymerase chain reaction-allele specific oligonucleotide in Koreans. 933 90

The base pair substitution mutational profiles induced by the heterocyclic amine cooked food mutagens PhlP and IQ in Salmonella typhimurium strains TA100 and TA1535 were determined by colony hybridization analysis. Both PhlP and IQ induced predominantly GC-->TA transversions in strain TA100 (rfa,delta uvrB/pKM101) with a pronounced preference for the second codon position (CCC--> CAC; 72% of total). PhlP also reverted strain TA1535 (rfa, delta uvrB) efficiently at concentrations similar to those required for strain TA100. In contrast to the PhlP-induced mutational profile observed in strain TA100, in strain TA1535 PhlP induced exclusively GC-->AT transitions at the second codon position (CCC-->CTC; 96-99% of total). Base substitution mutagenesis induced by heterocyclic amines related to PhlP is generally SOS-dependent, requiring the presence of plasmid pKM101 in Salmonella hisG46 strains. Thus, the SOS dependent reversion of S. typhimurium strain TA100 probably reflects error-prone lesion bypass at the major PhlP- guanosine adduct at the C-8 position. The GC-->AT transition mutations induced by PhlP in strain TA1535 appear to be SOS-independent, however, suggesting that these mutations may arise from the formation of PhlP-DNA adducts other than the replication-blocking C8-dG lesion.
Environ Mol Mutagen 1998
PMID:Specificity of base substitution mutations induced by the dietary carcinogens 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhlP) and 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) in Salmonella. 965 41

We recently described an untranslated CTG expansion that causes a previously undescribed form of spinocerebellar ataxia (SCA8). The SCA8 CTG repeat is preceded by a polymorphic but stable CTA tract, with the configuration (CTA)(1-21)(CTG)(n). The CTG portion of the repeat is elongated on pathogenic alleles, which nearly always change in size when transmitted from generation to generation. To better understand the reduced penetrance and maternal penetrance bias associated with SCA8 we analyzed the sequence configurations and instability patterns of the CTG repeat in affected and unaffected family members. In contrast to other triplet repeat diseases, expanded alleles found in affected SCA8 individuals can have either a pure uninterrupted CTG repeat tract or an allele with one or more CCG, CTA, CTC, CCA or CTT interruptions. Surprisingly, we found six different sequence configurations of the CTG repeat on expanded alleles in a seven generation family. In two instances duplication of CCG interruptions occurred over a single generation and in other instances duplications that had occurred in different branches of the family could be inferred. We also evaluated SCA8 instability in sperm samples from individuals with expansions ranging in size from 80 to 800 repeats in blood. Surprisingly the SCA8 repeat tract in sperm underwent contractions, with nearly all of the resulting expanded alleles having repeat lengths of <100 CTGs, a size that is not often associated with disease. These en masse repeat contractions in sperm likely underlie the reduced penetrance associated with paternal transmission.
Hum Mol Genet 2000 Sep 01
PMID:SCA8 CTG repeat: en masse contractions in sperm and intergenerational sequence changes may play a role in reduced penetrance. 1095 51

Mutations of the Smad2 and Smad4 genes, identified as mediators of the transforming growth factor-beta pathway, were investigated in lung adenocarcinomas induced by N-nitrosobis(2-hydroxypropyl)amine (BHP) in rats. Male Wistar rats, 6 wk old, were given 2000 ppm BHP in their drinking water for 12 wk and maintained without additional treatment until killed at week 25. Total RNA was extracted from 12 adenocarcinomas, and mutations in Smad2 and Smad4 were investigated by reverse transcription-polymerase chain reaction restriction single-strand conformation polymorphism analysis followed by sequencing analysis. In Smad2, single adenocarcinomas showed a GGC to GAC (Gly to Asp) transition at codon 100 and an AAG to GAG (Lys to Glu) transition at codon 383. In Smad4, one adenocarcinoma exhibited a TTC to CTC (Phe to Leu) transition at codon 214. These results suggest that mutations of Smad2 and Smad4 may play roles in a limited fraction of lung adenocarcinomas induced by BHP in rats.
Mol Carcinog 2000 Oct
PMID:Mutations of the Smad2 and Smad4 genes in lung adenocarcinomas induced by N-nitrosobis(2-hydroxypropyl)amine in rats. 1107 5

Calcium level in organelles of the slime mold Physarum polycephalum was monitored by chlortetracycline, a low-affinity calcium indicator. It was found that 2,5'-di(tertbutyl)-1,4,-benzohydroquinone (BHQ) at a concentration of 100 microM, but not the highly specific inhibitor of sarco-endoplasmic reticulum Ca2+-ATPase (SERCA), thapsigargin (1-10 microM), elicited calcium release from the CTC-stained intracellular calcium pool. Ionomycin also caused a calcium release (23.7+/-5.1%), which was less than that induced by BHQ (30.1+/-6.0%). Procaine (10 mM), a blocker of ryanodine receptor, completely abolished the responses to BHQ and ionomycin. Another blocker, ryanodine (100 microM), only slightly diminished the responses to ionomycin and BHQ. Apparently, BHQ and ionomycin acting as a Ca2+-ATPase inhibitor and an ionophore, respectively, elicit an increase in [Ca2+]i, which in turn triggers a calcium-induced calcium release (CICR) via the ryanodine receptor. Caffeine, an activator of ryanodine receptor, at a concentration of 25-50 mM produced a Ca2+-release (5.6-16.0%), which was not similar in magnitude to CICR. The response to 25 mM caffeine was only moderately inhibited by 25 mM procaine, and almost completely abolished by 50 mM procaine and 100 microM ryanodine.
Comp Biochem Physiol A Mol Integr Physiol 2001 Feb
PMID:Ionomycin and 2,5'-di(tertbutyl)-1,4,-benzohydroquinone elicit Ca2+-induced Ca2+ release from intracellular pools in Physarum polycephalum. 1122 89

This study was designed to localize adenosine receptors and to provide evidence that specific receptors are active only in either uncapacitated or capacitated mouse spermatozoa, where they play a role in regulating cAMP production. Using specific antibodies, stimulatory A(2A) receptors were localized primarily on the acrosomal cap region and the flagellar principal piece. Interestingly, the staining was much more pronounced in uncapacitated than in capacitated spermatozoa, suggesting capacitation-dependent changes in epitope accessibility. A(1) receptors showed a very similar distribution, but the staining was markedly greater in capacitated than in uncapacitated cells. After addition of purified decapacitation factor (DF) to capacitated cells, strong staining for A(2A) was regained, suggesting reversibility in epitope accessibility. Chlortetracycline analysis revealed that an agonist specific for A(2A) receptors had no detectable effect on capacitated cells, but after DF-induced decapacitation, the agonist then stimulated capacitation. That agonist also significantly stimulated cAMP production in uncapacitated cells, had no effect on capacitated cells, but regained the ability to stimulate cAMP in the latter following DF treatment. In contrast, an A(1) agonist inhibited cAMP in capacitated cells. These results indicate that specific adenosine receptors function in a reversible manner in one or other capacitation state, resulting in regulation of cAMP.
Mol Reprod Dev 2002 Oct
PMID:Capacitation state-dependent changes in adenosine receptors and their regulation of adenylyl cyclase/cAMP. 1220 35


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