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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two classes of amyloid beta-protein precursors which differ by the presence of a serine protease inhibitor domain have been described. We have used synthetic oligonucleotide probes to investigate the tissue distribution and cellular localization of mRNAs encoding the two classes of amyloid beta-protein precursors. RNA blot analysis showed that transcripts encoding the protease inhibitor sequence are ubiquitously expressed in peripheral and central tissues. By contrast, transcripts lacking the protease inhibitor domain were only found in the central nervous system. By in situ hybridization on cerebral cortex and hippocampal formation both types of transcripts were present exclusively in nerve cells and they appeared to be produced by the same cells. A reduction in the transcript lacking the protease inhibitor domain was observed in frontal cortex from Alzheimer's disease patients. The present results indicate that there exists no correlation between the distribution of amyloid amyloid beta-protein precursor mRNAs and the tissue and cellular pathology of Alzheimer's disease; they also suggest that an overproduction of amyloid beta-protein precursor mRNA is unlikely to be responsible for amyloid beta-protein deposition in Alzheimer's disease.
Brain Res Mol Brain Res 1989 Nov
PMID:Expression and cellular localization of amyloid beta-protein precursor transcripts in normal human brain and in Alzheimer's disease. 251 8

Streptomyces coelicolor A3(2) contains CCC DNA molecules, 2.6 kb in size, with an average copy number of less than one per ten chromosomes. Southern hybridisation revealed, in addition, two linear, integrated copies (A and B) of this "mini-circle" sequence per chromosome. The two integrated copies have similar (if not identical) ends and are present in the same locations in various S. coelicolor A3(2) derivatives. The mini-circle sequence is absent from S. lividans 66 and S. violaceolatus ISP5438 and from several Streptomyces species less closely related to S. coelicolor A3(2). None of a variety of Streptomyces plasmids tested contained homology to the mini-circle sequence. When a 1.8 kb fragment of the mini-circle lacking the ends of the integrated copies was inserted into KC515 (a derivative of the temperate phage phi C31 which is unable to lysogenise host strains by the natural route because the phage attachment site has been deleted) the resulting phage lysogenized S. coelicolor A3(2) (integrating into the genome of this host by homologous recombination with resident minicircle sequences) but not S. lividans or a variety of other phi C31 hosts. In contrast, a KC515 derivative (KC591) carrying the entire 2.6 kb mini-circle sequence linearized at its single BclI site (and therefore containing the integration site of the free mini-circle) lysogenized not only S. coelicolor A3(2) but also S. lividans 66 and most other strains normally lysogenized by phi C31. The KC591 lysogens of the eight Streptomyces species tested contained a linear, integrated prophage with termini apparently identical to those of the linear mini-circle copies of S. coelicolor.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Gen Genet 1986 Apr
PMID:A 2.6 kb DNA sequence of Streptomyces coelicolor A3(2) which functions as a transposable element. 301 83

We determined the physical and transcriptional organisation of the set of previously cloned biosynthetic genes involved in the production of the polyketide antibiotic actinorhodin by Streptomyces coelicolor A3(2). Complementation and mutational cloning analyses (in part using new phi C31 phage vectors incorporating a transcriptional terminator to block transcription from vector promoters into the cloned DNA) indicate that all the biosynthetic genes, including at least one regulatory (activator) gene, are clustered in a chromosomal region of about 26 kb. The genes are organised in at least four separate transcription units, ranging in size from 1 kb for the class III gene, to a polycistronic transcript of at least 5 kb for the class I, VII and IV genes. Indirect evidence shows that resistance to actinorhodin is also determined by the cloned DNA.
Mol Gen Genet 1986 Oct
PMID:Physical and genetic characterisation of the gene cluster for the antibiotic actinorhodin in Streptomyces coelicolor A3(2). 302 60

A number of deletions in the glucose kinase (glk) region of the Streptomyces coelicolor chromosome were found among spontaneous glk mutants. The deletions were identified by probing Southern blots of chromosomal DNA from glk mutants with cloned glk DNA. The deletions ranged in size from 0.3 kb to greater than 2.9 kb. When cloned glk DNA was introduced on a phi C31 phage vector into a glk mutant that contained a deletion of the entire homologous chromosomal glk region, glucose kinase activity was detected in extracts of these cells. The entire coding information for at least a subunit of glucose kinase is therefore present on the cloned glk DNA. The 0.3 kb glk chromosomal deletion was used to demonstrate that transfer of chromosomal glk mutations on to the phi C31::glk phage could occur by recombination in vivo. Since glk mutations frequently arise from deletion events, a method was devised for inserting the cloned glk DNA at sites in the chromosome for which cloned DNA is available, and thus facilitating the isolation of deletions in those DNA regions. phi C31::glk vectors containing a deletion of the phage att site cannot lysogenize S. coelicolor recipients containing a deletion of the glk chromosomal gene unless these phages contain S. coelicolor chromosomal DNA. In such lysogens, the glk gene becomes integrated into the chromosome by homologous recombination directed by the chromosomal insert on the phage DNA. In appropriate selective conditions, mutants which contain deletions of the glk gene that extend into the adjacent host DNA can be easily isolated. This method was used to insert glk into the methylenomycin biosynthetic genes, and isolate derivatives with deletions of host DNA from within the prophage into the adjacent host DNA. Phenotypic and Southern blot analysis of the deletions showed that there are no genes essential for methylenomycin biosynthesis for at least 13 kb to the left of a region concerned with negative regulation of methylenomycin biosynthesis. Many of the deletions also removed part of the phi C31 prophage.
Mol Gen Genet 1987 Jan
PMID:The glucose kinase gene of Streptomyces coelicolor and its use in selecting spontaneous deletions for desired regions of the genome. 303 39

Rodent-human somatic cell hybrids have been constructed which contain fragments of human chromosome 21 as their only human material. This was done by irradiating rodent-human somatic cell hybrids containing a complete chromosome 21 to fragment the genome and then rescuing human GAR synthetase and various amounts of flanking chromosome 21 DNA by fusing with GAR synthetase-deficient hamster cells and selecting for growth in purine-free medium. Four irradiation-reduction hybrids were produced by this method and contain the distal, proximal, and central portions of the long arm of human chromosome 21, all centered about GAR synthetase. These irradiation-reduction hybrids were used as a panel to regionally map single-copy and individual copies of repetitive sequences. Using these hybrids along with another independently constructed hybrid, the GAR synthetase gene was mapped distal to SOD-1 and proximal to CP21G1(D21S60). Of special interest is the regional mapping of the gene for the amyloid beta-protein distal to pPW236B(D21S11) and proximal to SOD-1.
Somat Cell Mol Genet 1988 May
PMID:Irradiation-reduced human chromosome 21 hybrids. 316 26

A concept that considers the causative nature of the so-called "slow virus infections", causing syndromes of spongiform encephalopathies in man and animals as a chain autocatalytic process is put forward. According to this concept, PrP(27-30) protein, isolated recently from the brains of scrapie-infected animals, is a C-terminal domain of the normal protein component of brain tissue which is a latent zimogen. Certain clinical and experimental data are discussed within the framework of this concept. Exogenous proteinases are presumed to be capable of triggering such a chain autocatalytic process in the brains of susceptible animals. Indeed, in one of our experiments, a subtoxic dose of pronase injected into mouse brain induced the development of a syndrome indistinguishable from spongiform encephalopathy in its clinical and pathomorphological manifestations. The probable role of neuron-specific proteins of intermediate filaments in such pathological processes is discussed. It seems possible that spongiform encephalopathies are particular cases of pathological processes that have catalytic nature. Presumably, the Alzheimer disease has such a catalytic causative nature.
Mol Biol (Mosk)
PMID:[Autocatalytic nature of "slow virus infections"]. 354 57

Glucose kinase in Streptomyces coelicolor has a molecular weight of about 110,000. In crude extracts, the enzyme exhibited apparent Km values of 0.20 mM for ATP, 0.27 mM for glucose, and 2.2 mM for the glucose analogue 2-deoxyglucose. Mutations (glk) to 2-deoxyglucose-resistance, which greatly reduce glucose kinase activity and result in relief of glucose repression of utilisation of various carbon sources, were mapped between proA and hisA in the S. coelicolor linkage map. Glucose kinase activity, 2-deoxyglucose-sensitivity, glucose utilisation and glucose repression, were all restored to glk mutants by a 3.5 kb DNA fragment cloned from S. coelicolor into a phage vector (phi C31 KC515), and by larger (10-30 kb) fragments cloned into a low copy number plasmid vector (pIJ916). The glk gene was further localised to a 2.9 kb BclI fragment of the cloned DNA by sub-cloning. Part or all of this fragment was present in each of five primary plasmid clones tested.
Mol Gen Genet 1984
PMID:Genetic mapping, cloning and physiological aspects of the glucose kinase gene of Streptomyces coelicolor. 609 78

Nonessential region responsible for G function has been identified in theta C31 phage genome by means of deletion mutants. The mutant phenotype is expressed upon theta C31 phage propagation in Streptomyces albus G strains differing in functioning of restriction and modification systems. Based on their increased resistance to EDTA, deletions were located in theta C31 delta 10 and theta C31 delta 65 phage mutants. Data are presented on physical mapping of nonessention region of theta C31 phage. The total length of this region is 24.1% of the overall length of DNA molecules. The DNA segment of 19.1% of the whole genome contains overlapped deletions. Theta C31 actinophage is proposed to be used as a cloning vector for Streptomyces. Various deletion mutants obtained, with the capacity of about 3 thousands base pairs may serve as "insertion vectors". The presence of the stretched nonessential genome region allows to use theta C31 phage as a "replacement vector". Then, insertion of foreign DNA to replace the EcoRI--C fragment of theta C31 DNA of 6.4 x 10(3) base pairs is possible. The phages comprising hybrid molecules may be selected for G and Lyg phenotypes.
Mol Biol (Mosk)
PMID:[Physical mapping of actinophage Streptomyces coelicolor A3(2). VI. The use of deletion mutants of actinophage phi C31 for construction of phage vectors]. 628 84

Glycerol-3-phosphate dehydrogenase (gylB) mutations (which cause glycerol sensitivity), and presumed glycerol kinase (gylA) and/or regulatory mutations eliminating both glycerol-3-phosphate dehydrogenase and glycerol kinase activities, map close to the argA locus of Streptomyces coelicolor A3(2). Using the plasmid vector pIJ702 and restriction enzymes BglII and SstI, extensively overlapping S. coelicolor DNA fragments of 2.74 kb and 2.84 kb were isolated, either of which could restore the wild-type phenotype to gylB and some gylA mutants. Genetic and biochemical analyses of mutants carrying the cloned gyl DNA suggested that a functional gyl promoter had not been cloned, and that restoration of the Gyl+ phenotype was achieved by recombination between the cloned and chromosomal gyl DNA sequences. After subcloning parts of this DNA into the phage vector phi C31 KC400, "gene disruption" analysis was carried out, which confirmed the absence of the gyl promoter, and indicated that a polycistronic mRNA traverses gylA and then gylB.
Mol Gen Genet 1984
PMID:The glycerol utilization operon of Streptomyces coelicolor: genetic mapping of gyl mutations and the analysis of cloned gylDNA. 631 46

Mutants of temperate actinophage phi C31 Streptomyces coelicolor A3(2) having an increased resistance to chelating agents (sodium EDTA and sodium citrate) were isolated. Most of these mutants were not able to lysogenize sensitive cultures (c-mutants). DNA molecules of four c-mutants resistant to chelating agents were shown to be deleted by electron microscopy of DNA heteroduplexes. The four deletions were located in the central region of phi C31 DNA molecule. The deleted segment of 1000 base pairs common for molecules of all c-mutants is located in a region 47,2--49,9% and indicates the position of c-region on the physical map of phi C31 actinophage. The size of the region containing delections of all analyzed c-mutants is 1700 base pairs. The c-region on the heteroduplex map was oriented in relation to the known genetic map of phi C31.
Mol Biol (Mosk)
PMID:[Physical mapping of Streptomyces coelicolor A3(2) actinophage DNA. I. Location of the c-region of actinophage phiC31]. 677 85


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