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)

Four solid-colour revertants were isolated from the highly variegated niv-53::Tam1 mutant, in which the transposable element Tam1 is integrated in the promoter region of the chalcone synthase (chs) gene. DNA sequence analysis revealed that in all four lines the Tam1 element was deleted together with flanking nucleotides of the chs promoter. In one case the TATA box of the chs gene was removed resulting in extremely low expression of the gene, and initiation of transcription occurring at a new position. The other three deletions defined a sequence motif (TAC-CAT) which is apparently required for maximal gene expression. Thus transposable elements seem to be useful for probing gene structure, in this case the signal structure in the promoter region, by virtue of imprecise excision.
Mol Gen Genet 1988 Jan
PMID:Transposon-induced alterations in the promoter region affect transcription of the chalcone synthase gene of Antirrhinum majus. 283 Apr 68

The denV gene of bacteriophage T4 was reconstituted from two overlapping DNA fragments cloned in M13 vectors. The coding region of the intact gene was tailored into a series of plasmid vectors containing different promoters suitable for expression of the gene in E. coli and in yeast. Induction of the TAC promoter with IPTG resulted in overexpression of the gene, which was lethal to E. coli. Expression of the TACdenV gene in the absence of IPTG, or the use of the yeast GAL1 or ADH promoters resulted in partial complementation of the UV sensitivity of uvrA, uvrB, uvrC and recA mutants of E. coli and rad1, rad2, rad3, rad4 and rad10 mutants of S. cerevisiae. The extent of denV-mediated reactivation of excision-defective mutants was approximately equal to that of photoreactivation of such strains. Excision proficient E. coli cells transformed with a plasmid containing the denV gene were slightly more resistant to ultraviolet (UV) radiation than control cells without the denV gene. On the other hand, excision proficient yeast cells were slightly more sensitive to killing by UV radiation following transformation with a plasmid containing the denV gene. This effect was more pronounced in yeast mutants of the RAD52 epistasis group.
Mol Gen Genet 1986 Apr
PMID:Partial complementation of the UV sensitivity of E. coli and yeast excision repair mutants by the cloned denV gene of bacteriophage T4. 352 Feb 42

We investigated prolactin (PRL) degradation in rat liver lysosomes both in vivo and in vitro. In previous studies we showed that, in addition to the Golgi apparatus, PRL is internalized towards lysosomes and light, lysosome-like vesicles which we identified as 'prelysosomes'. Injected [125I]oPRL that localized in lysosomes and prelysosomes at times varying from 0 to 45 min showed significant differences from fresh and plasma membrane- (PM) or Golgi-bound hormone. First, it was more easily dissociable by 3 M MgCl2 than Golgi- but less than PM-bound [125I]oPRL. Second, it was only in lysosomal fractions that, as time following injection increased, a significant part of dissociable radioactivity became non-TAC-precipitable. When MgCl2-extracted [125I]oPRL was subjected to gel filtration on a Sephadex G-75 fine column, some of the radioactivity, and especially that extracted from prelysosomal or lysosomal fractions, eluted as a high molecular weight (HMW) entity, most co-migrated with fresh [125I]oPRL, and a little was found in small fragments. Only the central peak had any rebinding activity, which was comparable to that of fresh hormone. In an in vitro study we incubated [125I]hGH with lysosomal fractions for 16 h at 25 degrees C. After centrifugation, an aliquot of supernatant hormone was assayed for its binding capacity to standard receptor preparations and the rest subjected to gel filtration. Peak fractions were also tested in binding assay. [125I]hGH that had been in contact with prelysosomes lost almost all of its ability to bind to standard receptors and totally migrated in the HMW peak, at the void volume of the column.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Cell Endocrinol 1984 Apr
PMID:Intracellular transformation of prolactin following internalization into rat liver. 632 76

Mitochondrial mutants of the green alga Chlamydomonas reinhardtii that are inactivated in the cytochrome pathway of respiration have previously been isolated. Despite the fact that the alternative oxidase pathway is still active the mutants have lost the capacity to grow heterotrophically (dark + acetate) and display reduced growth under mixotrophic conditions (light + acetate). In crosses between wild-type and mutant cells, the meiotic progeny only inherit the character transmitted by the mt- parent, which indicates that the mutations are located in the 15.8 kb linear mitochondrial genome. Two new mutants (dum-18 and dum-19) have now been isolated and characterized genetically, biochemically and at the molecular level. In addition, two previously isolated mutants (dum-11 and dum-15) were characterized in more detail. dum-11 contains two types of deleted mitochondrial DNA molecules: 15.1 kb monomers lacking the subterminal part of the genome, downstream of codon 147 of the apocytochrome b (COB) gene, and dimers resulting from head-to-head fusion of asymmetrically deleted monomers (15.1 and 9.5 kb DNA molecules, respectively). As in the wild type, the three other mutants contain only 15.8 kb mitochondrial DNA molecules. dum-15 is mutated at codon 140 of the COB gene, a serine (TCT) being changed into a tyrosine (TAC). dum-18 and dum-19 both inactivate cytochrome c oxidase, as a result of frameshift mutations (addition or deletion of 1 bp) at codons 145 and 152, respectively, of the COX1 gene encoding subunit I of cytochrome c oxidase. In a total of ten respiratory deficient mitochondrial mutants characterized thus far, only mutations located in COB or COX1 have been isolated.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Gen Genet 1995 Nov 15
PMID:Mutations affecting the mitochondrial genes encoding the cytochrome oxidase subunit I and apocytochrome b of Chlamydomonas reinhardtii. 750 Sep 39

RPE.40 mutant cells differ from wild-type Chinese hamster ovary (CHO-K1) cells in their increased resistance to Pseudomonas exotoxin A and their inability to process the insulin proreceptor and certain viral envelope proproteins. Northern analysis revealed that RPE.40 cells maintained a substantially lower steady-state level of 4.0 kb fur mRNA than did CHO-K1 cells. Analysis of fur cDNAs showed that RPE.40 cells were diploid at the fur locus, and RPE.40 cells had a Cys (TGC) to Tyr (TAC) mutation in codon 196 of one allele (allele I). Approximately 25-30% of the CHO-K1 cells were also heterozygous (Tyr/Cys) at codon 196, and pre-mRNAs transcribed from the second allele (allele II) in RPE.40 cells were defectively spliced. All other pre-mRNAs were correctly spliced. Rapid turnover of defectively spliced transcripts may account for the reduced steady-state level of fur mRNA observed in RPE.40 cells. Our results provide a mechanistic basis for the endoprotease-deficient phenotype of RPE.40 cells.
Somat Cell Mol Genet 1995 Jan
PMID:Analysis of mutations in alleles of the fur gene from an endoprotease-deficient Chinese hamster ovary cell strain. 760 55

All mitochondrial tRNAs in the protozoan Leishmania are believed to be encoded in the nuclear genome and imported selectively into the mitochondria by an as yet unknown mechanism. Previously, we reported that two tRNAs whose genes are tightly linked were imported by mitochondria. In contrast, a tRNA encoded by a lone tRNA gene was not detectable in mitochondria. The lone tRNA gene had flanking sequences that were different from the linked genes. These studies implied a possible correlation between tRNA gene organization and gene flanking sequence, and selective tRNA import into mitochondria. Here, we report the identification of a cluster of 10 tRNA genes and show the distribution of the corresponding tRNAs in cytosolic and mitochondrial fractions. tRNA(leu)(CAG) and tRNA2(arg)(TCG) are abundant in the cytosol, but relatively scarce in mitochondria. Conversely, tRNA(ile)(TAT) and tRNA1(lys)(TTT) are abundant in mitochondria, but relatively scarce in the cytosol. tRNA(val)(TAC) and tRNA2(thr)(TGT) are barely detectable in either cellular compartment, while tRNA(gln)(TTG), tRNA1(arg)(ACG), tRNA(gly)(TCC), and tRNA(trp)(CCA) are detected in approximately equal levels in both compartments. Sequencing of the 2600 bp that comprise the tRNA gene cluster also encoding the genes for 5S RNA and URNAB RNA indicates that nucleotide composition, length, and location of genes within the cluster do not clearly correlate with import characteristics. The unexpected presence of the tRNA(trp)(CCA)-gene transcript in mitochondria is also reported. Evidence suggests that this tRNA may have unidentified base modifications at the anticodon triplet.
Mol Biochem Parasitol 1994 May
PMID:A nuclear tRNA gene cluster in the protozoan Leishmania tarentolae and differential distribution of nuclear-encoded tRNAs between the cytosol and mitochondria. 793 26

Somatic mutations in the retinoblastoma-1 gene (RB1) and loss of RB1 protein function have been implicated in a number of human malignancies, but the role of RB1 gene and protein abnormalities in ductal pancreatic cancer (DPCA) is virtually unknown. We therefore analyzed expression of the RB1 protein immunohistochemically and/or by western blotting in a total of 54 sporadic and eight familial cases of archival and frozen DPCA and in 18 pancreatic carcinoma cell lines by using the antibodies RB-WL-1, 84-B3-1, and PMG3-245. Mutations in the RB1 promotor region and exons 13-21 of the RB1 gene were likewise examined by single-strand conformation polymorphism (SSCP) analyses and DNA sequencing of genomic DNA from 30 microdissected primary pancreatic tumors and the pancreatic carcinoma cell lines. Moreover, amplification and expression of a major regulatory component of RB1 function, cyclin D1, were assessed by southern and immunohistochemical analyses, respectively. The DPCAs were heterogeneous in both the intensity of RB1 nuclear staining and the percentage of immunoreactive cells. The tumors often had areas where RB1 staining was weak or absent adjacent to normal pancreatic tissue; however, only two of 32 archival cases and one of 30 frozen cases of DPCA completely lacked RB1 nuclear staining. Immunohistochemical and western blot analyses of 18 pancreatic carcinoma cell lines demonstrated the absence of RB1 expression in only two cell lines, Capan-1 and QGP-1. Analyses of the RB1 gene and promotor region by SSCP and DNA sequencing largely confirmed the immunochemical findings. Three of 30 primary carcinomas had abnormalities revealed by SSCP analyses. In one case a single base-pair deletion was confirmed in exon 18 and resulted in premature termination and the absence of detectable RB1 protein. A second case had TAC-->TTC missense mutation in exon 13. The third primary carcinoma could not be reliably sequenced because it had a low percentage of epithelial cells. The cyclin D1 gene was not amplified in any of the primary pancreatic tumors or cell lines examined. These immunochemical and molecular analyses of the RB1 tumor suppressor gene and cyclin D1 proto-oncogene in a large series of human pancreatic cancers and cell lines indicate that RB1 and cyclin D1 alterations occur during the development of some human DPCAs. Nevertheless, it is probable that alterations in cell-cycle regulation in DPCAs more frequently involve pathways other than those involving RB1 and cyclin D1.
Mol Carcinog 1996 Feb
PMID:Molecular and immunochemical analyses of RB1 and cyclin D1 in human ductal pancreatic carcinomas and cell lines. 859 83

Tris-hydroxymethyl-amino-methane telomers bearing a fluorinated end have recently been proposed as potential drug carriers. Using ion microscopy, we have investigated the cell uptake and subcellular distribution of a perfluorinated telomere, called F-TAC, in two cell lines, malignant murine B16 melanoma and normal rat skin fibroblasts. Single layer cell cultures on gold plates were incubated with F-TAC at different concentrations. Ion microscopy using mass spectrometry enabled the detection of Fluorine 19 atoms entering into F-TAC constitution. This microanalytical study showed an elective cytoplasmic localization of the molecule, wherein the distribution is relatively homogeneous. Within same culture and incubation conditions, intercellular variations in F-TAC content were very low. In the malignant line, the intracellular concentration remains practically identical when increasing F-TAC concentration in the culture medium above 0.2 mg/ml, indicating that the uptake phenomenon is saturable. In conclusion, the F-TAC telomer easily crosses the plasma membrane, however, it has difficulties in crossing the nuclear membrane. It is likely that intracellular penetration is essentially due to rapid endocytosis of the telomer.
Cell Mol Biol (Noisy-le-grand) 1996 May
PMID:Subcellular distribution of a new fluorinated, biocompatible, non-ionic telomeric carrier: a study in cultured B16 melanoma and rat skin fibroblasts. 879 88

Androgen insensitivity syndrome (AIS) is associated with a wide range of quantitative or qualitative defects in the androgen receptor (AR). In some patients with AIS, however, no defects are detectable in the ligand-binding properties of the AR. We have analyzed the ARs of two unrelated patients with this category (termed 'receptor-positive type') of AIS. Sequence analysis of these patients' AR gene revealed single amino acid substitutions (579Cys(TGC)-->Phe(TTC) and 582Phe(TTC)-->Tyr(TAC)) in exon B encoding the first zinc finger of the DNA-binding domain of the AR. These mutations have not been previously reported. Moreover, cotransfection assays and mobility shift assays revealed that these patients' mutant ARs had defective transcriptional activity of the target gene because of impaired DNA-binding ability to the androgen-responsive element. These findings strongly indicate that these mutations are responsible for the pathogenesis of AIS in these patients.
Mol Cell Endocrinol 1996 Jun 18
PMID:Androgen insensitivity syndrome due to new mutations in the DNA-binding domain of the androgen receptor. 880 34

The sequence specificity of DNA-binding by monoaza- and diaza-anthracenedione analogues of mitoxantrone (MX) has been investigated by DNase 1 footprinting and spectroscopic techniques. More than 100 sites cut by the enzyme were sequenced on three pBR 322 and simian virus 40 DNA restriction fragments. Different inhibition and stimulation effects were observed as a function of the structural properties of each drug. A gradual change was found from MX to monoaza derivatives and from these to diaza derivatives, corresponding to a broader distribution of drug-inhibited regions. In addition to almost all sites found with MX (38 of 44), 29 new inhibition sites were observed using the diaza compound BBR 2894. The sequence analyses in terms of base doublets or triplets confirm the preference of MX for alternating pyrimidine-purine sites, the most significant triplet sequences being (5' to 3') CTA, GCA, TAC, ACT, CAC and TTA. In addition to MX sites, BBR 2894 seemed to bind efficiently to pyrimidine-pyrimidine-pyrimidine or purine-pyrimidine-pyrimidine triplets containing CT or TC motifs. Differential cleavage plots essentially confirmed the above results. Spectrophotometric and chiroptical studies showed a decreased DNA-binding affinity and a modified geometry of intercalation when nitrogen replaces carbon in the anthraquinone ring. These results can be useful for understanding the substantially different biological responses exhibited by aza-substituted anthracenedlones when compared with their non-substituted, pharmacologically relevant congeners.
Mol Pharmacol 1996 Oct
PMID:Aza-bioisosteres of 9, 10-anthracenedione: a modulation of DNA sequence specificity. 886 28


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