Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0004135 (ATM)
13,001 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Herpes simplex virus type 1 (HSV-1) subgenomic sequences from 0.743 to 0.782 map units have been molecularly cloned as plasmid AT1 and shown to inhibit stable DNA-mediated gene transformation of Ltk- cells with the HSV-1 thymidine kinase (tk) gene. Here it is shown that AT1 also inhibits transient gene expression. Expression from the chloramphenicol acetyltransferase (CAT) gene under the control of either the HSV-1 tk gene or the Rous sarcoma virus (RSV) promoter was inhibited when cotransfected into Ltk- and CV-1 cells with equimolar amounts of AT1. AT1 was subcloned as three overlapping plasmids called AT1a, alpha 27 and AT1b. The alpha 27 plasmid encodes the HSV-1 immediate early gene, alpha 27; AT1a possesses sequences that specify an open reading frame in HSV-1 strain KOS used in these studies, although the significance of this open reading frame is unknown; AT1b possesses the sequences for UL55 and UL56, also genes for which no function has been reported. No single subclone or pair of subclones demonstrated significant inhibition of transient gene expression. Cotransfection of all three subclones did result in inhibition of RSV-CAT gene expression, suggesting that information from each subclone is necessary. One of the three subclones, alpha 27, contains the HSV-1 immediate early gene, alpha 27, so the possibility that other immediate early genes could substitute for alpha 27 was tested. Inhibition of RSV-CAT gene expression was also achieved by cotransfection of AT1a and AT1b with either an alpha 0- or alpha 4-containing plasmid, suggesting that the role of the alpha 27-containing plasmid can be replaced by other alpha genes with trans-regulating capability. Finally, AT1a and AT1b linker insertion mutants have been constructed and used to study the role these plasmids play in mediating inhibition. These results suggest that AT1 contains HSV-1 functions in addition to that of alpha 27 that interfere with gene expression.
J Gen Virol 1991 Jan
PMID:Inhibition of transient gene expression with plasmids encoding herpes simplex virus type 1 UL55 and alpha genes. 184 42

The Aspergillus nidulans gene coding for acetamidase (amdS) was introduced into A. niger by transformation. Twelve Amd+ transformants were analysed genetically. The amdS inserts were located in seven different linkage groups. In each transformant the plasmid was integrated in only a single chromosome. Our (non-transformed) A. niger strains do not grow on acetamide and are more resistant to fluoroacetamide than the transformants. Diploids hemizygous for the amdS insert have the Amd+ phenotype. We exploited the opportunity for two-way selection in A. niger: transformants can be isolated based on the Amd+ phenotype, whereas counter-selection can be performed using resistance to fluoroacetamide. On this basis we studied the phenotypic stability of the heterologous amdS gene in A. niger transformants as well as in diploids. Furthermore, we mapped the plasmid insert of transformant AT1 to the right arm of chromosome VI between pabA1 and cnxA1, providing evidence for a single transformational insert. The results also show that the amdS transformants of A. niger can be used to localize non-selectable recessive markers and that the method meets the prerequisites for efficient mitotic mapping. We suggest the use of amdS transformants for mitotic gene mapping in other fungi.
Mol Gen Genet 1990 Jul
PMID:Genetic analysis of amdS transformants of Aspergillus niger and their use in chromosome mapping. 227 31

Two plasmids that overproduce the colicin A lysis proteins, Cal, are described. Plasmid AT1 was constructed by a deletion in the colicin A operon, which placed the cal gene near a truncated caa gene in such a way that both gene products wer synthesized at high levels following induction. Plasmid CK4 was constructed by insertion of the cal gene downstream from the tac promoter of an expression vector. Overproduction of Cal was obtained after mitomycin C induction of pAT1 cells and after IPTG induction of pCK4 cells. The kinetics of Cal synthesis were examined with [35S] methionine and [2-3H] glycerol in lpp or lpp+ host strains. Each of the steps of the lipid modification and maturation pathway of Cal was demonstrated. The modified precursor form of overproduced Cal was not chased as efficiently as when it is produced in pColA cells. After treatment with globomycin, a significant amount of this modified precursor form accumulated and was degraded with time into smaller acylated proteins, but without release of the signal peptide. Release of cellular proteins and quasi-lysis were observed after about 1 hour of induction for cells containing either plasmid. In addition, in Cal-overproducing cells, the rate of quasi-lysis was increased but not its extent. In pldA cells, quasi-lysis was reduced but not abolished. Lethality of the Cal induction in the overproducing cells was in th same range as that in wild-type cells.
Mol Gen Genet 1989 Jun
PMID:High-level expression of the colicin A lysis protein. 250 57

A subclone of an SV40-transformed fibroblast cell line from a patient with Ataxia telangiectasia (AT) with a relatively high rate of DNA uptake was isolated. However, more than 65000 independent genomic transfectants (using wild-type human DNA) did not contain the functional AT gene. This number represents the statistical distribution of an amount of DNA equivalent to more than three times the haploid human genome. The transfectants were screened by an X ray selection protocol that could rescue a single wild-type cell out of a population of 10(6) AT cells. This suggests a reversion frequency for AT of below 10(-8). The DNA uptake into human cells is compared with that into NIH3T3 cells and future possibilities for the isolation of human repair genes are discussed.
Mol Gen Genet 1988 Jun
PMID:Ataxia telangiectasia resists gene cloning: an account of parameters determining gene transfer into human recipient cells. 284 42

Methylnitronitrosoguanidine (MNNG) is reported to inhibit DNA synthesis in intact human cells, in the cells from patients with ataxia telangiectasia (AT) or the cells from two rodent species. DNA synthesis in different cell lines exhibits varying sensitivity to MNNG inhibitory effect. 4-5-fold higher concentrations of MNNG are required for 50% inhibition of DNA synthesis in AT cells or in field vole cells as compared with the concentration required for human cells or Chinese hamster. The different compactness of two chromatin fractions might possibly result in lower sensitivity of DNA synthesis in heterochromatin to MNNG-induced inhibition as compared with the sensitivity of euchromatin. The genetic expression of AT defect on the cellular level is supposed to be connected with changes in supramolecular packaging of chromatin in interphase nuclei.
Mol Gen Mikrobiol Virusol 1985 Sep
PMID:[The effect of methylnitronitrosoguanidine on DNA synthesis in human and animal cells. Inhibition of DNA synthesis in asynchronous and synchronous cultured cells]. 391 33

Recombination frequencies for two sets of genetic markers of herpes simplex virus were determined in various host cells with and without ultraviolet irradiation of the virus. UV irradiation increased the recombination frequency in all the cell types studied in direct proportion to the unrepaired lethal damage. In human skin fibroblasts derived from a patient with xeroderma pigmentosum (XP) of complementation group A, a given dose of UV stimulated recombination more than that in fibroblasts from normal individuals. On the other hand, UV stimulation of HSV recombination was slightly less than normal in fibroblasts derived from a patient with a variant form XP and from an ataxia telangiectasia patient. Caffeine, an agent known to inhibit repair of UV damage, reduced recombination in most of the cell types studied and did not suppress the UV-induced increase in recombination. These findings suggest that for virus DNA with the same number of unrepaired UV-lesions, each of the tested cell types promoted HSV-recombination to an equivalent extent.
Mol Gen Genet 1980
PMID:Genetic recombination of herpes simplex virus, the role of the host cell and UV-irradiation of the virus. 624 34

Human skin fibroblasts derived from a healthy individual and from a child with the genetic disorder ataxia telangiectasia were infected with herpes simplex virus type 1 (HSV-1). The virus infection did not affect the synthesis of procollagen but inhibited its release from the cells.
J Gen Virol 1980 Nov
PMID:HSV-1 infection inhibits procollagen and protein secretion from normal and ataxia telangiectasia cultured skin fibroblasts. 625 35

Isolated glomeruli from the rainbow trout Oncorhynchus mykiss have been examined for the presence of receptors specific for angiotensin II (AII). Specific binding of 125I-Asp1Val5-AII was saturable, plateaued after 20 min, and increased with glomerular protein. Saralasin (Sar1Val5Ala8-AII), a nonselective peptide AII receptor antagonist of AII binding to mammalian tissues, was a poor inhibitor of 125I-Asn1Val5-AII binding to trout glomeruli. However, the nonpeptide antagonist, Losartan (= DuP 753), which is specific for AII subtype AT1 receptors in mammalian tissues, was an effective inhibitor of binding of both 125I-Asp1Val5-AII and 125I-Asn1Val5-AII to trout glomeruli. The IC50 for Losartan inhibition of binding of Asp1Val5-AII was 1.25 +/- 0.07 x 10(-8) M while that for inhibition of binding of Asn1Val5-AII was 2.73 +/- 0.45 x 10(-8) M. Statistical analysis of logistic curve fits confirmed the easier displacement of Asp1Val5-AII than of Asn1Val5-AII. PD 123177, a nonpeptide antagonist specific for AII subtype AT2 receptors in mammalian systems, was ineffective as an antagonist of AII binding to trout glomeruli. These results are consistent with the presence of a specific AII receptor in the trout glomerulus and imply a novel receptor configuration.
Gen Comp Endocrinol 1993 Oct
PMID:Characterization of putative glomerular receptors for angiotensin II in the rainbow trout Oncorhynchus mykiss using the antagonists Losartan, PD 123177, and saralasin. 826 54

Angiotensin II exerts its action via at least two distinct receptor subtypes designated AT1 and AT2. AT1 receptors seem to be responsible for most of the known angiotensin II effects while the role of AT2 receptors is not yet clear. Adipocytes of adult rats express exclusively the AT1 subtype. Angiotensin II stimulates prostacyclin release in adult rat adipocytes and in mouse preadipocytes. In the latter prostacyclin release is completely blocked by an AT2 receptor antagonist. Adipocyte angiotensin II receptors seem to be regulated by age and fat mass. Blockade of these receptors by an AT1 antagonist seems to prevent adipose tissue hypertrophy. Moreover, adipose tissue contains all the main components of the renin-angiotensin system such as angiotensinogen, angiotensin converting enzyme, angiotensin II and angiotensin II receptors. Angiotensinogen expression in adipocytes is stimulated by a high fat diet concurrent with enlargement of fat mass, associated with insulin resistance. Angiotensin converting enzyme inhibitors improve insulin sensitivity. Taken together, there is evidence of interaction between insulin and angiotensin II in regulation of adipose tissue metabolism and cellularity. Clarification of these interactions could lead to significant progress in pharmacological treatment of obesity and its comorbidity.
Gen Physiol Biophys 1995 Oct
PMID:The role of angiotensin II and its receptors in regulation of adipose tissue metabolism and cellularity. 878 38

Two genes that are highly expressed in the tomato shoot apex have been cloned by differential hybridization. One of the deduced polypeptides (AT1) shows significant similarities to class II proteinase inhibitors, while the other (AT2) displays similarities to defensins. Transcripts of both genes are also detectable in the developing flower and are present only in minor amounts in other tissues tested. In situ hybridization analysis revealed that both genes are expressed in non-overlapping subsets of cells in the shoot apex, as well as in the developing flower. The potential use of these genes as markers for certain cell types and the possible biological function of the encoded proteins are discussed.
Mol Gen Genet 1996 Aug 27
PMID:Expression of genes for a defensin and a proteinase inhibitor in specific areas of the shoot apex and the developing flower in tomato. 880 87


1 2 3 Next >>