Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.7.7.48 (transcriptase)
9,479 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The ability of DNA polymerases (pols) to catalyze the template-directed synthesis of duplex oligonucleotides containing a nonstandard Watson-Crick base pair between a nucleotide bearing a 5-(2,4-diaminopyrimidine) heterocycle (d kappa) and a nucleotide bearing either deoxyxanthosine (dX) or N1-methyloxoformycin B (pi) has been investigated. The kappa-X and kappa-pi base pairs are jointed by a hydrogen bonding pattern different from and exclusive of those joining the AT and GC base pairs. Reverse transcriptase from human immunodeficiency virus type 1 (HIV-1) incorporates dXTP into an oligonucleotide opposite d kappa in a template with good fidelity. With lower efficiency and fidelity, HIV-1 reverse transcriptase also incorporates d kappa TP opposite dX in the template. With d pi in the template, no incorporation of d kappa TP was observed with HIV reverse transcriptase. The Klenow fragment of DNA pol I from Escherichia coli does not incorporate d kappa TP opposite dX in a template but does incorporate dXTP opposite d kappa. Bovine DNA pols alpha, beta, and epsilon accept neither dXTP opposite d kappa nor d kappa TP opposite d pi. DNA pols alpha and epsilon (but not beta) incorporate d kappa TP opposite dX in a template but discontinue elongation after incorporating a single additional base. These results are discussed in light of the crystal structure for pol beta and general considerations of how polymerases must interact with an incoming base pair to faithfully copy genetic information.
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PMID:Recognition by viral and cellular DNA polymerases of nucleosides bearing bases with nonstandard hydrogen bonding patterns. 754 38

In the present study, we analyzed human adult brain, fetal spinal cord, and an interleukin-2 (IL-2)-responsive human oligodendroglioma subclone, TC620.6A2, for the presence of mRNAs for the alpha, beta, and gamma chains of the interleukin-2 receptor (IL-2R alpha, IL-2R beta, and IL-2R gamma). IL-2R beta mRNA, but not IL-2R alpha or IL-2R gamma was detectable by Northern blot analysis in adult human brain tissues. Northern blot analysis of TC620.6A2 and human fetal tissues revealed mRNAs of 1.5 kb and 1.3 kb that hybridized to the IL-2R alpha cDNA at low to medium stringency. Reverse transcriptase-polymerase chain reaction (RT-PCR) experiments were done on the TC620.6A2 cell line utilizing primers to IL-2R alpha, IL-2R beta, and IL-2R gamma. Southern blot analysis of the TC620.6A2 RT-PCR reactions detected products identical in size to the peripheral blood lymphocyte (PBL) positive controls at high stringency. Several of the TC620.6A2 IL-2R alpha, IL-2R beta, and IL-2R gamma cDNAs were cloned and sequenced. The sequences were found to be identical to the known IL-2R sequences. To our knowledge, these experiments are the first to demonstrate the presence of authentic IL-2R mRNAs in a human oligodendrocyte-like cell line. Demonstration of mRNA for IL-2R beta in human adult brain, IL-2R alpha in fetal brain, and IL-2R alpha, IL-2R beta, and IL-2R gamma in a malignant neural cell line suggests the possibility of a role for IL-2/IL-2R interactions in development and disease.
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PMID:Molecular cloning of IL-2R alpha, IL-2R beta, and IL-2R gamma cDNAs from a human oligodendroglioma cell line: presence of IL-2R mRNAs in the human central nervous system. 853 Jan 86

Microtubules play an essential role in cell division. Little is known about possible variations of total tubulin and tubulin isotype expression during the cell cycle. We analyzed the total tubulin content, tubulin polymerization status and tubulin isotype content in resting and dividing human K562 leukemic cells and human MES-SA sarcoma cells. Although the total cellular tubulin content increases as the cells progress toward mitosis, the total tubulin/total protein ratio is stable during the cell cycle. Reverse transcriptase-polymerase chain reaction was applied to analyze the levels of expression of alpha, beta, and gamma-tubulin isotypes. Whereas alpha-tubulin isotype and gamma-tubulin transcripts were found to be expressed at constant levels throughout the cell cycle, some of the beta-tubulin isotype transcripts were found to be more highly expressed in dividing then in resting cells. Both of the class IV beta-tubulin isotype transcripts (human 5 beta and beta 2, Class IVa and IVb, respectively) were expressed in dividing K562 and MES-SA cells at twice the levels found in resting cells. Increased expression of the class IV isotype proteins in dividing cells was confirmed by immunoblotting, both in K562 and in MES-SA cells. A larger fraction of total cell tubulin was found to be polymerized in dividing cells (36-40%) than in resting cells (27-30%). The degree of polymerization of class IV tubulin in dividing and resting cells was similar to that of total tubulin. These results show that total tubulin is expressed as constant levels throughout the cell cycle but that the degree of polymerization is increased as cells are committed to division. The relative overexpression of the two class IV beta-tubulin isotypes in dividing cells suggests functional specificity for these isotypes and a regulatory role of these isotypes on the microtubule network during mitosis.
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PMID:Differential expression of tubulin isotypes during the cell cycle. 887 65

Protein kinase C (PKC), a key component of the signaling pathways leading to proliferation and differentiation, consists of a family closely related serine/threonine protein kinases. The mRNA expression of these PKC isoforms has been characterized during hematopoietic differentiation. Using the reverse-transcriptase polymerase chain reaction technique, we have analyzed the levels of isoform transcripts in bone marrow CD34(+) hematopoietic progenitors and their progeny differentiated along erythroid, megakaryocyte, or granulocyte/monocyte lineages, upon exposure to growth factors. In contrast with isoforms alpha, beta(I), beta(II), delta, and epsilon, ubiquitously expressed, isoforms theta, eta/L, zeta, and iota/lambda exhibited a lineage-restricted expression. These qualitative changes, which allow to distinguish the erythroid and megakaryocyte phenotypes from the granulocyte/monocyte phenotype, include zeta exclusively upregulated in granulocytes/monocytes and theta, eta/L, and iota/lambda exclusively expressed in megakaryocytes and erythroblasts. In contrast, erythroblasts and megakaryocytes, which supposedly share a common bipotential progenitor, displayed only quantitative changes. These results evidence the selective expression of PKC isoforms at transcriptional and/or posttranscriptional levels in hematopoietic progenitors induced to differentiate, which may suggest a differential contribution of individual isoforms to cellular signaling.
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PMID:Differential expression of protein kinase C isoform transcripts in human hematopoietic progenitors undergoing differentiation. 1051 25

Laminins are a family of disulfide-linked heterotrimeric proteins consisting of 3 different subunits termed alpha, beta, and gamma chains. Combinations of 11 characterized laminin subunits (alpha 1-alpha 5, beta 1-beta 3, and gamma 1-gamma 3) generate at least 12 laminin isoforms, which can serve different functions. Although expression of laminin in the hematopoietic microenvironment has been known for many years, the nature of the laminin isoforms present in the human bone marrow is poorly characterized. The present study attempts to clarify this issue. Reverse transcriptase-polymerase chain reaction analysis of human bone marrow stromal cells suggested the expression of many laminin isoforms in the marrow. Northern blot and immunoblot analysis, however, showed that laminin-8/9 and laminin-10/11 are the most abundant laminin isoforms synthesized by human bone marrow stromal cells. Other isoforms, if present, certainly play a minor role in the hematopoietic microenvironment. Functionally, laminin-10/11 preparations showed strong adhesive interactions with human CD34(+) cell lines. Antibodies against the beta 1 integrin subunit inhibited these interactions. Other laminin isoforms, especially laminin-1 and laminin-2/4, showed only weak or no adhesive interactions with the hematopoietic cell lines tested, explaining former negative results. In addition to its adhesion-mediating properties, laminin-10/11 preparations also showed a mitogenic activity for human hematopoietic progenitor cells. Taken together, these data suggest that laminin in the bone marrow plays a hitherto unexpected important function in the development of hematopoietic progenitor cells. (Blood. 2000;96:4194-4203)
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PMID:Characterization and functional analysis of laminin isoforms in human bone marrow. 1111 Jun 91

Systemic pseudohypoaldosteronism type I (PHAI) is an autosomal recessive disorder that arises from loss of function mutations of the alpha, beta, or gamma subunit of Epithelial Na(+) Channel (ENaC). In addition to a severe renal phenotype in the neonatal period, patients with PHAI develop a childhood pulmonary syndrome characterized by cough and frequent respiratory infections. We tested a patient, born to consanguineous parents, who presented with dehydration, metabolic acidosis, hyperkalemia, elevated renin and aldosterone levels at birth, and recurrent respiratory symptoms in his first year. He demonstrated defective epithelial Na(+) transport in multiple organs (raised sweat Cl(-), 120 mM; raised salivary Na(+) and Cl(-), 118 and 111 mM, respectively; and little nasal amiloride-sensitive potential difference). No deleterious mutation was identified in the coding region of the three ENaC subunits. Reverse transcriptase-polymerase chain reaction of nasal epithelial RNA showed reduced betaENaC expression, and inability to amplify promoter elements indicated the possibility of a deletion in the 5' region. Using a probe that corresponded to exon 1A of betaENaC, we confirmed a large deletion (> 1,300 bp). In summary, a homozygous mutation in the promoter region of betaENaC leads to PHAI, the first description of a mutation in the regulatory regions of an ENaC subunit leading to a clinical phenotype.
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PMID:Systemic pseudohypoaldosteronism from deletion of the promoter region of the human Beta epithelial na(+) channel subunit. 1220 93

Previous studies using whole-cell recording methods suggest that human B lymphocytes express an amiloride-sensitive, sodium-permeable channel. The present studies aim to determine whether this channel has biophysical properties and a molecular structure related to the alpha, beta, and gamma subunits of the epithelial sodium channel (ENaC). Reverse transcriptase polymerase chain reaction and Northern blots showed that human B lymphocytes express messages for both alpha- and beta- but not gamma-ENaC. Western blots showed that both alpha- and beta- but not gamma-ENaC proteins are expressed and strongly reduced by antisense oligonucleotides. Patch clamp experiments demonstrated that lymphocyte sodium channels are not active in cell-attached patches. However, membrane stretch can activate a 21-pS nonselective cation channel. The frequency of observance of this channel was significantly reduced by antisense oligonucleotide against alpha-ENaC but not by antisense oligonucleotide against beta-ENaC, indicating that only the alpha subunit of ENaC is necessary to form stretch-activated cation channels. Aldosterone (1.5 microm) reduced the frequency of observance of 21-pS alpha-ENaC channels and simultaneously induced the appearance of spontaneously active 10-pS channels. Antisense oligonucleotide experiments showed that this 10-pS channel is formed from alpha- and beta-ENaC. After expression of exogenous gamma-ENaC, aldosterone again reduced the frequency of observance of the 21-pS alpha-ENaC channel but induced the appearance of a 5-pS channel, presumably a alphabetagamma-ENaC channel. In the absence of aldosterone, the alpha subunit forms an alpha-cryptic channel that is activated by stretch, and in the presence of aldosterone, beta and alpha subunits together form an active channel that is modulated by aldosterone.
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PMID:Steroids and exogenous gamma-ENaC subunit modulate cation channels formed by alpha-ENaC in human B lymphocytes. 1518 80

Retinoids have shown significant activities in cancer prevention and therapy. Many of their effects are mediated by nuclear retinoid receptors including retinoic acid receptors (RARs alpha, beta and gamma) and retinoid X receptors (RXRs alpha, beta and gamma). Human retinoic acid receptor beta (RARbeta) has three different isoforms: beta1, beta2 and beta4. The tumor suppressive characteristics of RARbeta2, its silencing by promoter hypermethylation, and its reexpression following demethylation have been reported. In contrast, RARbeta1, an embryonic isoform with restricted expression in adult tissues has been linked to carcinogenesis. However, factors regulating RARbeta1 expression have not yet been clarified. During studies on the head and neck squamous cell carcinoma cells, we found that the expression of RARbeta increased in cells grown to high density. Real-time reverse-transcriptase polymerase chain reaction revealed that the isoform increased in these cells was RARbeta1. Epigenetic modifications of this isoform were tested using combined bisulfite restriction analysis and chromatin immunoprecipitation assays. The UMSCC38 cell line showed significant RARbeta1 expression (p < 0.001), which was dependent on cell density and culture duration. The increased expression of RARbeta1 was not due to demethylation of its promoter. However, higher cell densities were associated with increased acetylation of histone 3 at lysine 9 in RARbeta1 but not in RARbeta2. These findings reveal that the expression of RARbeta1 is regulated by cell density through changes in histone acetylation.
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PMID:Regulation of RARbeta1 expression in head and neck cancer cells by cell density-dependent chromatin remodeling. 1546 35

In researches involving in vitro protein synthesis and self-replication system, Qbeta replicase is one of the key enzymes, which are demanded for the high availability. Qbeta replicase is a RNA-dependent RNA polymerase of Qbeta coliphage. It consists of four subunits (alpha, beta, gamma, and delta subunit), where the beta-subunit is encoded by the viral genome, while the other three subunits are host proteins normally involved in protein synthesis, namely, ribosomal protein S1 (alpha), elongation factors EF-Tu (gamma) and EF-Ts (delta). To increase the production of the Qbeta replicase holoenzyme, several types of expression vectors, including pKK, pET and others, were employed to produce Qbeta replicase. However, the beta-subunit was almost in the precipitate fraction. Considering that the four subunits of Qbeta replicase holoenzyme are in equivalent molar ratio and the amount of the subunits, ribosomal S1 and EF-Ts, being produced by the host cells is relatively low, co-expression of beta-subunit with the other three subunits was performed to know whether the availability of the host subunits is the contributing factor for the solubility of the Qbeta replicase. pBAD33-rep was constructed by cloning the beta-subunit gene into pBAD 33, a pACYC derivative, and pET21a(+) was employed as expression vector for the three other subunits. Among the different combinations of co-expression experiments, solubility was found to slightly increase by SDS-PAGE analysis when the beta-subunit was co-expressed with EF-Tu-Ts. And the replicase activity assay showed this soluble enzyme is in active form. The expression of beta-subunit was enhanced by decreasing the level of inducer IPTG in co-expression, and more soluble enzyme were obtained.
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PMID:[Co-expression of beta-subunit with other subunits of Qbeta replicase]. 1611 Sep 60

The transcription factors CCAAT enhancer-binding protein alpha, beta, and delta, and peroxisome proliferator-activated receptor gamma are known to be crucial to the differentiation of adipocytes and are expressed in sebaceous gland cells. As lipogenesis is key to both adipocyte and sebocyte differentiation we hypothesize that sebocytes follow a similar program of differentiation to adipocytes. We have investigated the expression of known adipogenic factors resistin, galectin-12, sterol response-element-binding protein-1 (SREBP-1) and stearoyl-CoA desaturase in the immortalized sebaceous gland cell line SZ95 and whole skin. Reverse transcriptase-PCR analysis showed the expression of galectin-12, resistin, SREBP-1, and stearoyl-CoA desaturase mRNAs in SZ95 sebocytes. Immunoreactivity was observed for galectin-12 and SREBP-1 in the nuclei and resistin in the cytoplasm of basal sebocytes, and stearoyl CoA desaturase in the cytoplasm of basal and luminal sebocytes of human scalp skin. Expression of galectin-12, resistin, and SREBP-1 in SZ95 sebocytes was confirmed by Western blot analysis. These data provide further evidence that pathways of differentiation in adipocytes and sebocytes could be similar and therefore further understanding of sebaceous gland differentiation and lipogenesis and potential therapies for sebaceous gland disorders may be obtained from our knowledge of adipocyte differentiation.
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PMID:Expression of lipogenic factors galectin-12, resistin, SREBP-1, and SCD in human sebaceous glands and cultured sebocytes. 1736 19


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