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At least 505 records · Page 28Linked to original sources
PubMed2002

Reciprocal regulation of beta(1)-adrenergic receptor gene transcription by Sp1 and early growth response gene 1: induction of EGR-1 inhibits the expression of the beta(1)-adrenergic receptor gene.

The beta(1)-adrenergic receptor (beta(1)-AR) plays a key role in regulating heart rate and contractility in response to catecholamines. Our studies have focused on defining the factors that regulate the expression of the beta(1)-AR gene. We determined that a 65-base-pair (bp) region in the beta(1)-AR promoter between bp -394 and bp -330 directs basal transcription. An element located between -377 and -365 can bind Sp1 and Sp3. In Drosophila melanogaster SL2 cells, Sp1 stimulated the expression of the beta(1)-AR promoter, whereas Sp3 was unable to activate transcription. Site-directed mutagenesis indicated that an intact Sp1-binding site is essential for maintaining the activity of the basal promoter. In addition to binding Sp family members, the nucleotides between -381 and -367 can bind the zinc-finger transcription factor Egr-1. The Egr-1 and Sp1 binding sites are partially overlapping and their binding sequence is conserved among mammalian beta(1)-AR genes. The induction of Egr-1 in rat neonatal ventricular myocytes with phorbol-12-myristate-13-acetate or in HeLa S3 cells by regulated expression of Egr-1 in a tetracycline-responsive promoter, suppressed expression from the beta(1)-AR promoter. Overexpression of Sp1 in SK-N-MC cells increased beta(1)-AR mRNA by 2.4-fold, whereas overexpression of Egr-1 reduced beta(1)-AR mRNA by 40%. Coexpression of Egr-1 with Sp1 reduced Sp1-mediated up-regulation of beta(1)-AR mRNA by 60%. Mutagenesis revealed that an intact Sp1-binding site is essential for observing transcriptional repression by Egr-1 and that Egr-1 suppressed the transcription of the beta(1)-AR gene by competing with Sp1 for binding to their overlapping sites. These results reveal a novel physiologically relevant transcriptional mechanism for reciprocal regulation of beta(1)-AR gene expression.

Animals↗
PubMed1980

Identification of new genes in a cell envelope-cell division gene cluster of Escherichia coli: cell division gene ftsQ.

We report the identification, cloning, and mapping of a new cell division gene, ftsQ. This gene formed part of a cluster of three division genes (in the order ftsQ ftsA ftsZ) which itself formed part of a larger cluster of at least 10 genes, all of which were involved in some step in cell division, cell envelope synthesis, or both. The ftsQAZ group was transcribed from at least two independent promoters.

Cell Division↗
PubMed1997

A mouse gene (Dgcr6) related to the Drosophila gonadal gene is expressed in early embryogenesis and is the homolog of a human gene deleted in DiGeorge syndrome.

We report the identification of a mouse gene, Dgcr6, which shows high sequence similarity to gonadal (gdl), a Drosophila gene of unknown function. Dgcr6 is the mouse homolog of human DGCR6, previously shown to be deleted in DiGeorge syndrome, a developmental field defect affecting the derivatives of the pharyngeal arches which is associated with 22q11.2 deletions. The Dgcr6 transcript has a 594 nucleotide open reading frame (ORF) encoding 198 amino acids. We previously mapped Dgcr6 to mouse chromosome 16B1-B3, a region known to contain other mouse homologs of genes deleted in DiGeorge syndrome. Expression studies were performed by Northern blotting analysis on mouse embryo and adult tissues and by RNA in situ hybridization on mouse embryo sections. Results show that Dgcr6 transcripts are abundant during mouse embryogenesis, from at least 7 days post coitum. In particular, high expression was detected in the brain, spinal cord and pharyngeal arches. On adult tissues high expression was detected in testis. The function of Dgcr6 is to be determined, but its developmental expression suggests that this gene may play a role in the developmental defects associated with 22q11.2 deletions.

Amino Acid Sequence↗
PubMed2002

Cloning of the maltose phosphorylase gene from Bacillus sp. strain RK-1 and efficient production of the cloned gene and the trehalose phosphorylase gene from Bacillus stearothermophilus SK-1 in Bacillus subtilis.

The maltose phosphorylase (MPase) gene of Bacillus sp. strain RK-1 was cloned by PCR with oligonucleotide primers designed on the basis of a partial N-terminal amino acid sequence of the purified enzyme. The MPase gene consisted of 2,655 bp encoding a theoretical protein with a Mr of 88,460, and had no secretion signal sequence, although most of the MPase activity was detected in the culture supernatant of RK-1. This cloned MPase gene and the trehalose phosphorylase (TPase) gene from Bacillus stearothermophilus SK-1 were efficiently expressed intracellularly under the control of the Bacillus amyloliquefaciens alpha-amylase promoter in Bacillus subtilis. The production yields were estimated to be more than 2 g of enzyme per liter of medium, about 250 times the production of the original strains, in a simple shake flask. About 60% of maltose was converted into trehalose by the simultaneous action of both enzymes produced in B. subtilis.

Amino Acid Sequence↗
PubMed2006

HVJ-based non-viral gene transfer method: successful gene therapy using HGF and VEGF genes in experimental ischemia.

VEGF and HGF are pleiotropic factors that regulate cell growth, cell motility, and morphogenesis of various types of cells. The receptors of these growth factors are expressed in neurons and endothelial cells, and are identified as neurotrophic, neuroprotective, and angiogenic factors. Indeed, gene therapy using viral vectors encoding the VEGF or HGF gene has been reported to be effective for preventing the expansion of ischemic injury. However, the safety issue of viral vectors is a major problem in clinical application. To overcome this problem, we have developed an HVJ-based non-viral vector, which achieves high-efficiency transfection rates of viral vectors with the safety of liposomes. This review discusses the feasibility of gene therapy using an HVJ-based non-viral vector containing the VEGF or HGF gene for cerebral ischemia.

Animals↗
PubMed1994

The rhesus macaque beta 1-adrenergic receptor gene: structure of the gene and comparison of the flanking sequences with the rat beta 1-adrenergic receptor gene.

We have cloned the gene for the rhesus macaque beta 1-adrenergic receptor. In addition to the protein coding block, we have sequenced its 5' (1424 bp) and 3' (1534 bp) flanking regions and aligned them with comparable sections of the rat beta 1-adrenergic receptor gene. The rhesus macaque gene contains a 1440 bp open reading frame which codes for a deduced protein of 480 amino acids that is 95% and 89% similar to the human and rat beta 1-adrenergic receptors, respectively. The rhesus macaque beta 1-adrenergic receptor contains conserved sites for potential N-linked glycosylation and cAMP-dependent protein kinase phosphorylation identified within the human and rat receptors, but differs in the structure and length of the third cytoplasmic loop. The 400 bases of 5' flanking sequence proximal to the protein coding block are highly conserved (84% similarity) between the rat and rhesus macaque genes. The entire 3' flanking sequence, which extends beyond two potential polyadenylation sites at 1050 and 1337 bp relative to the translation termination codon, is also highly conserved between the two species. Comparison of the flanking sequences of the two species reveals conserved regulatory sequences which may be important for beta 1-adrenergic receptor expression and transcriptional modulation.

Amino Acid Sequence↗
PubMedDate not supplied

Differential efficacy of suicide gene therapy by herpes simplex virus-thymidine kinase gene reflects the status of p53 gene in human esophageal cancer cells.

We examined the effect of herpes simplex virus-thymidine kinase gene (HSV-TK)-mediated suicide gene therapy on human esophageal cancer. Two human lines, T.Tn cells which bears truncated p53 and TE2 cells with wild-type p53, were transduced with the HSV-TK gene and tested for their sensitivities to a prodrug, ganciclovir (GCV). The transduced cells, T.Tn/TK and TE2/TK, increased in vitro sensitivity to GCV compared with that of respective wild-type cells. However, the growth suppression of T.Tn/TK tumors induced by GCV was marginal in nude mice and the tumors regrew thereafter. In contrast, the growth of TE2/TK tumors was significantly inhibited by GCV and all the tumors disappeared. The status of the p53 gene of tumor cells thereby may influence the efficacy of the HSV-TK/GCV system.

Animals↗
PubMed1991

[Gene diagnosis of adult polycystic kidney disease--linkage analysis between APKD gene and alpha-globin gene 3'HVR].

Genomic DNA PvuII fragments containing the 3'HVR from 52 unrelated Chinese of Han nationality varied between 1.7 kb and 10.0 kb and showed high polymorphism. The genomic DNA PvuII fragments from five families with adult polycystic kidney disease (APKD) were analyzed using the alpha-globin gene 3' HVR (hypervariable region) as probe. The results showed a close linkage between 3'HVR and the APKD gene and segregation according to Mendelian laws. The maximum Lod score for linkage between 3' HVR and APKD was 3.372 at a recombination fraction theta = 0.01. The alpha-globin gene 3'HVR probe can therefore be used for presymptomatic gene diagnosis and prenatal diagnosis in the Han ethnic group.

DNA Probes↗
PubMed1988

Human creatine kinase genes on chromosomes 15 and 19, and proximity of the gene for the muscle form to the genes for apolipoprotein C2 and excision repair.

The human chromosomal assignments of genes of the creatine kinase (CK) family--loci for brain (CKBB), muscle (CKMM), and mitochondrial (CKMT) forms--were studied by Southern filter hybridization analysis of DNAs isolated from a human x rodent somatic cell hybrid clone panel. Probes for the 3'-noncoding sequences of human CKBB and CKMM hybridized concordantly only to DNAs from somatic cell hybrids containing chromosomes 14 and 19, respectively. Thus the earlier assignment of the gene coding for the CKBB isozyme to chromosome 14 was confirmed by molecular means, as was the provisional assignment of CKMM to the long arm of chromosome 19. A probe containing canine sequences for CKMM cross-hybridized with human sequences on chromosomes 14 and 19, a result consistent with the assignments of CKBB and CKMM. A probe containing human sequences for CKMT enabled the provisional assignment of CKMT to human chromosome 15. Independent hybrids with portions of the long arm of chromosome 19 missing indicated the order of genes on the long arm of chromosome 19 as being cen-GPI-(TGFB, CYP1)-[CKMM, (APOC2-ERCC1)]-(CGB, FTL). The unexpectedly more distal location of APOC2 among the genes on the long arm--and APOC2's close association with CKMM--is discussed with respect to the close linkage relationship of APOC2 to myotonic muscular dystrophy.

Animals↗
PubMedDate not supplied

Natural killer cells and gene therapy: potential of gene transfection for optimizing effector cell functions and for targeting gene products into tumor metastases.

Fluorescently labeled, adoptively transferred interleukin (IL)-2 activated natural killer (A-NK) cells have the ability to selectively accumulate within established pulmonary or hepatic metastases, binding to tumor cells and/or to microvascular endothelial cells. A-NK cells have also been shown to exert antimetastatic therapy in animal models and in the clinic. Transfection of genes for cytokines or possibly other molecules has the potential to improve the therapeutic potency and efficacy of the effector cells. Gene transfection to induce autocrine production of IL-2 and/or other cytokines is expected to augment their antimetastatic activities, while avoiding toxicity from systemic administration of high doses of cytokines. An alternative or complementary strategy for gene therapy is to transfect A-NK cells with genes for cytotoxic molecules, to selectively target them to metastatic sites.

Animals↗
PubMed1994

Identification of the gene encoding lipoate-protein ligase A of Escherichia coli. Molecular cloning and characterization of the lplA gene and gene product.

R(+)-Lipoic acid is a cofactor required for function of the alpha-keto acid dehydrogenase and glycine cleavage enzyme complexes. The naturally occurring form of lipoate is attached by amide linkage to the epsilon-amino group of a specific lysine residue within conserved lipoate-accepting protein domains. Lipoate-protein ligase(s) catalyze the formation of this amide bond between lipoyl groups and specific apoproteins. We report the isolation of the lplA gene which encodes an Escherichia coli lipoate-protein ligase. Strains with lplA null mutations transport lipoic acid normally but have severe defects in the incorporation and utilization of exogenously supplied lipoic acid and lipoic acid analogs. These strains are also highly resistant to selenolipoate (a growth-inhibiting lipoate analog) and contain no detectable lipoate-protein ligase activity in cell extracts. The lplA gene has been cloned, sequenced, and physically mapped to min 99.6 (4657 kilobases) of the E. coli chromosome. Upon overexpression, the 38-kDa lplA gene product was purified to homogeneity and shown to have a mass, N-terminal sequence and amino acid composition consistent with the deduced 337 residue primary sequence. Enzyme assays show that purified LplA catalyzes the ATP-dependent attachment of [35S]lipoic acid to apoprotein, thus confirming that lplA encodes lipoate-protein ligase A. Analysis of lplA null mutants also indicates the existence of a second (lplA-independent) lipoyl-ligase enzyme in E. coli. This is the first identification of a lipoate ligase gene and the first analysis of a purified lipoate ligase enzyme.

Amino Acid Sequence↗
PubMed1996

Increased expression of the insulin-like growth factor I (IGF-I) receptor gene in hepatocellular carcinoma cell lines: implications of IGF-I receptor gene activation by hepatitis B virus X gene product.

Hepatitis B virus infection is associated with acute and chronic liver disease and the development of hepatocellular carcinoma (hcc). Several lines of evidence have suggested that hepatitis B virus X protein (HBx), which is a transcriptional trans-activator, plays a role in the process of liver carcinogenesis. We have investigated the expression of insulin-like growth factor I (IGF-I) receptor in human hepatocellular carcinoma cell lines using SNU368 cells containing HBx and SNU387 cells, which lack HBx gene transcript (J-G. Park et al., Int. J. Cancer, 62: 276-282, 1995), in an attempt to understand its possible relationship to the HBx-induced hcc. The binding of 125I-labeled IGF-I to the SNU368 cells was 5-fold higher than that of SNU387 cells. The Scatchard analysis of the binding data revealed a single class binding site for IGF-I with Kd of 7.6 and 8.8 nM and maximum binding capacities of 169 and 33 fmol/10(5) cells, respectively. Therefore, the difference observed in 125I-labeled IGF-I binding between SNU368 and SNU387 cells was due to an increase in the number of IGF-I binding sites with no change in affinity for the IGF-I receptor. An enhanced level of IGF-I receptors in SNU368 cells was also observed by fluorescence-activated cell sorting analysis using a monoclonal antibody against human IGF-I receptor, alpha IR3. The level of IGF-I receptor RNA and the basal IGF-I receptor gene promoter activity in SNU368 cells were 5 and 10 times higher than those observed in SNU387 cells, respectively. To substantiate further that HBx could transactivate the expression of the endogenous IGF-I receptor gene, Hep G2 cells were transiently transfected with a HBx expression vector. The transfection of Hep G2 cells with an HBx expression vector resulted in increased levels of IGF-I receptor RNA, promoter activity, and 125I-labeled IGF-I binding by 2.6-, 2.8-, and 2-fold, respectively. As a result of higher levels of IGF-I receptor, the mitogenic effect of IGFs (IGF-I and IGF-II) on SNU368 cells was 6 times higher than that of SNU387 cells. These results suggest that HBx may play a role in the process of hcc by activating IGF-I receptor gene expression.

Carcinoma, Hepatocellular↗
PubMed1999

Search for susceptibility genes, gene x gene interactions, and gene x environment interactions utilizing nonparametric linkage analysis.

There may be a different genetic basis for the two forms of the disease simulated in Problem 2 and the complex disease may be affected by environmental factors. Hence, we investigate the effects of two environmental factors. We selected 400 nuclear families from the data generated for Problem 2. Affection status was investigated in several ways. Individuals with severe and mild forms of the disease were both considered affected, individuals with only the severe form were considered affected while those with the mild form were considered unknown, and individuals with only the mild form were considered affected while those with the severe form were considered unknown. We found evidence of linkage between putative disease loci and markers in the D3G042-D3G049 and D5G031-D5G042 regions when we considered severely and mildly affected individuals as affected and also in the region D1G004-D1G013 when mildly affected individuals were considered unknown. We observed interactions between the first environmental factor and D1G043 among healthy sib pairs.

Environment↗
PubMed2000

Disruption of six novel genes from chromosome VII of Saccharomyces cerevisiae reveals one essential gene and one gene which affects the growth rate.

Six ORFs of unknown function located on chromosome VII of Saccharomyces cerevisiae were disrupted in two different genetic backgrounds, and the phenotype of the generated mutants was analysed. Disruptions of ORFs YGR256w, YGR272c, YGR273c, YGR275w and YGR276c were carried out using the disruption marker kanMX4 flanked by short homology regions, whereas ORF YGR255c was inactivated with a long flanking homology (LFH) disruption cassette (Wach et al., 1994). Tetrad analysis of the heterozygous disruptants revealed that ORF YGR255c, previously identified as COQ6 and encoding a protein involved in the biosynthesis of coenzime Q (Tzagoloff and Dieckmann, 1990), is an essential gene. The same analysis also revealed that sporulation of the ygr272cDelta heterozygous diploid produced two small colonies per ascus that were also G418-resistant, indicating that the inactivation of ORF YGR272c could result in a slower growth rate. This result was confirmed by growth tests of the haploid disruptants and by complementation of the phenotype after transformation with a plasmid carrying the cognate gene. No phenotypes could be associated to the inactivation of ORFs YGR256w, YGR273c, YGR275w and YGR276c. Two of these genes have recently been further characterized: ORF YGR255w, renamed RTT102, encodes a regulator of the Ty1-element transposition, whereas ORF YGR276c was found to encode the 70 kDa RNase H activity and was renamed RNH70 (Frank et al., 1999).

Chromosomes, Fungal↗