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

c-myc mRNA contains at least two discrete sequence elements that account for its short half-life, one in the 3' untranslated region and the other in the carboxy-terminal coding region (coding-region determinant). To investigate the function of each determinant, one or both were fused in frame to portions of a gene encoding long-lived beta-globin mRNA. Each chimeric gene was stably transfected into HeLa and NIH 3T3 cells and was transcribed from a constitutive cytomegalovirus promoter or from a serum-regulated c-fos promoter, respectively. The steady-state levels of the chimeric mRNAs in exponentially growing HeLa cells were compared, and their half-lives were measured by two independent methods: (i) in actinomycin D-treated HeLa cells and (ii) after serum addition to starved 3T3 cells. By each method, mRNAs containing either instability determinant were less stable than beta-globin mRNA. mRNA containing only the c-myc 3' untranslated region was not significantly more stable than mRNA with both determinants. In a cell-free mRNA decay system containing polysomes from transfected HeLa cells, mRNA containing the coding-region determinant was destabilized by addition of a specific RNA competitor, whereas mRNA containing only the 3' untranslated region was unaffected. When a stop codon was inserted upstream of the coding-region determinant, the chimeric mRNA was stabilized approximately twofold. These and other data suggest that degradation involving the coding-region determinant occurs most efficiently when ribosomes are translating the determinant.
Mol Cell Biol 1994 Mar
PMID:The half-life of c-myc mRNA in growing and serum-stimulated cells: influence of the coding and 3' untranslated regions and role of ribosome translocation. 811 42

Latent cytomegalovirus (CMV) infection is often reactivated in the lung. We postulated that this reactivation could occur by stimulation of the CMV major immediate early (IE) promoter by other viruses that infect the lung. The specific aim of this study was to investigate whether adenovirus early proteins could stimulate the CMV IE promoter in inflammatory cells. We transfected the monocyte/macrophage THP-1 cell line and the T-lymphocyte Jurkat cell line with plasmids coding for adenovirus E1A 12S or 13S proteins, along with a plasmid containing the CMV IE promoter region linked to the chloramphenicol acetyltransferase (CAT) reporter gene. In unstimulated THP-1 cells, the E1A 13S gene product increased CMV IE CAT activity by 18-fold compared with cells containing the control E1A plasmid. This effect was not seen in cells transfected with the E1A 12S plasmid. There was a similar effect of the E1A 13S gene product in LPS-stimulated THP-1 cells. In unstimulated Jurkat cells, the E1A 13S gene product stimulated CMV IE CAT activity by 19-fold compared with cells containing the E1A control plasmid; the E1A 12S gene product had no effect. There was a similar effect of the 13S E1A gene product in phorbol myristate acetate-stimulated Jurkat cells. These findings demonstrate that the CMV IE promoter can be stimulated by early viral proteins of adenovirus in inflammatory cells. These observations could be important for understanding the reactivation of latent CMV infection.
Am J Respir Cell Mol Biol 1994 Apr
PMID:Adenovirus E1A 13S gene product up-regulates the cytomegalovirus major immediate early promoter. 813 60

Normal cells in culture exhibit limited division potential and have been used as a model for cellular senescence. In contrast, tumor-derived or carcinogen- or virus-transformed cells are capable of indefinite division. Fusion of normal human diploid fibroblasts with immortal human cells yielded hybrids having limited life spans, indicating that cellular senescence was dominant. Fusions of various immortal human cell lines with each other led to the identification of four complementation groups for indefinite division. The purpose of this study was to determine whether human chromosome 1 could complement the recessive immortal defect of human cell lines assigned to one of the four complementation groups. Using microcell fusion, we introduced a single normal human chromosome 1 into immortal human cell lines representing the complementation groups and determined that it caused loss of proliferative potential of an osteosarcoma-derived cell line (TE85), a cytomegalovirus-transformed lung fibroblast cell line (CMV-Mj-HEL-1), and a Ki-ras(+)-transformed derivative of TE85 (143B TK-), all of which were assigned to complementation group C. This chromosome 1 caused no change in proliferative potential of cell lines representing the other complementation groups. A derivative of human chromosome 1 that had lost most of the q arm by spontaneous deletion was unable to induce senescence in any of the immortal cell lines. This finding indicates that the q arm of human chromosome 1 carries a gene or set of genes which is altered in the cell lines assigned to complementation group C and is involved in the control of cellular senescence.
Mol Cell Biol 1994 Apr
PMID:A gene involved in control of human cellular senescence on human chromosome 1q. 813 34

This study addresses the effect of transcription on replication, using a system based on autonomously replicating plasmids in human cells. We added transcriptional elements from the human cytomegalovirus promoter/enhancer and the human beta-actin promoter to autonomously replicating plasmids based on human sequences and found that the transcriptional elements inhibited plasmid replication. Furthermore, conditional inhibition of plasmid replication was demonstrated by using a tetracycline-responsive promoter. We found that replication activity of plasmids carrying this promoter was inversely correlated with promoter activity. Replication activity was partially restored on plasmids when a transcriptional termination sequence was placed directly downstream of the promoter element. Transcriptional activity of the promoters and the efficacy of the terminator sequence were confirmed by using steady-state RNA analysis. These experiments suggest that transcription inhibits DNA replication on these plasmids and that the degree of inhibition is dependent on transcription strength. The possible significance of these results for chromosomal DNA replication are discussed.
Mol Cell Biol 1994 Apr
PMID:Transcription inhibits the replication of autonomously replicating plasmids in human cells. 813 54

Groups of 5'-phosphonates of natural 2'-deoxynucleosides and ribonucleosides were synthesized by condensation of 3'-acetylated 2'-deoxynucleosides or 2',3'-substituted (2',3'-O-isopropylidene, 2',3'-O-methoxymethylene, or 2',3'-O-ethoxymethylene) ribonucleosides. As condensing agents, either N,N'-dicyclohexylcarbodiimide or 2,4,6-triisopropylbenzenesulphonyl chloride were used. Nucleoside 5'-ethoxycarbonyl-phosphonates were converted into corresponding nucleoside 5'-aminocarbonylphosphonates by the action of ammonia in methanol. All compounds were tested for inhibition of several viruses, including human herpes simplex virus type 2 and cytomegalovirus, but showed no activity. A few compounds insignificantly inhibited human immunodeficiency virus type 1 reproduction. Thymidine 5'-hydrogenphosphonate neutralized the anti HIV action of 3'-azido-3'-deoxythymidine, thus indirectly showing that it could be partly hydrolyzed in cell culture to corresponding thymidine.
Mol Biol (Mosk)
PMID:[Ribonucleoside and 2'-deoxyribonucleoside 5'-phosphonates: synthesis and antiviral activity]. 814 53

The human cytomegalovirus (HCMV) gene UL97 product was shown to play an important role in phosphorylation of ganciclovir (GCV) in HCMV-infected cells. The deletion of the 4 amino-acid sequence AACR confers resistance to a laboratory mutant. The aim of this study was to develop a rapid and simple method to detect mutations within the 12 base pair (bp) fragment encoding AACR, from isolates and clinical specimens (urine, bronchoalveolar lavage, cerebral spinal fluid samples). A target region encompassing this 12bp sequence was amplified by a single-step PCR assay from HCMV isolates and reference strains, and a two-step procedure from clinical specimens. Reaction products were submitted to restriction enzyme analysis and dot-blot hybridization assay. Two biotinylated probes were used: one probe (DL) overlapping the 12bp region; and a control probe with similar length and GC content. Hybridization was performed under conditions allowing the detection of one bp deletion (HCMV strain susceptibility to GCV was determined by a rapid late antigen synthesis reduction assay.) The control probe hybridized to the UL97 sequence amplified from all 23 tested isolates and the reference strains. The DL probe gave a positive signal with GCV-susceptible strains; no signal was obtained for five out of seven resistant isolates, and for a laboratory mutant derived from the strain AD169. Restriction analysis of amplification products showed different patterns suggesting this region can be involved in various DNA changes.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Cell Probes 1993 Dec
PMID:Rapid detection of cytomegalovirus strains resistant to ganciclovir through mutations within the gene UL97. 814 79

Cytomegalovirus (CMV) is a member of the herpes virus group. Infection results in a variety of disorders which depend largely on the immune status of the host. A well known property of CMV is that after primary infection the virus persists in the body of the host resulting in latency. Severe immunodepression or immunodeficiency can cause reactivation of the virus from its latent state, leading to endogenous reinfection. In contrast to other herpes viruses, such as herpes simplex virus which persists in neurons, and Epstein Barr virus which persists in B lymphocytes, little is known about the localization of latent CMV. In order to obtain more insight in the organ or cell type serving as a reservoir for latent CMV, it is important to know more about the course of natural infection and the cells and organs involved. When more information is available about the localization of latent virus, studies concerning the physical state of viral DNA or the extent of viral transcription and/or translation will follow in the near future. In this review some properties of the epidemiology and transmission of human CMV, as well as data about acute infection will be given. In addition, some characteristics of the localization of latent CMV and the physical state of the virus will be discussed. Where necessary, particularly regarding insight into CMV-host interactions, knowledge of animal, particularly murine, rat and guinea pig CMV infections, will be discussed.
Virchows Arch B Cell Pathol Incl Mol Pathol 1993
PMID:Cytomegalovirus and latency: an overview. 814 53

Thromboxane A2, a potent platelet agonist and vasoconstrictor, exerts its actions via specific G protein-coupled receptors. cDNAs encoding the full length thromboxane receptor have been isolated from human placenta mRNA by reverse transcriptase-polymerase chain reaction. An expression construct, under control of the cytomegalovirus promoter, was introduced into human embryonic kidney 293 cells. Membranes from transfected cells bound the thromboxane antagonist SQ29,548 and the agonist [15-(1 alpha,2 beta(5z)-3 alpha(1E,3S)-4 alpha)]-7-[3-(3-hydroxy-4-(p- iodophenoxy)-1-butenyl)-7-oxabicyclo[2,2,1]hept-2-yl]-5-heptenoic acid) with high affinities, and significantly more receptors were expressed in these cells, compared with platelet preparations. The putative seventh transmembrane segment is highly related in all cloned members of the eicosanoid receptor family and forms a critical portion of the ligand binding pocket for G protein-coupled receptors. Several point mutations in this segment were generated. Binding of SQ29,548 was virtually abolished in cells transfected with all the variant receptor constructs. However, one receptor variant (TxR-W299L), in which a tryptophan at position 299 was substituted for a leucine residue, allowed a definite discrimination between agonist and antagonist binding sites in competition and saturation binding experiments. An antibody directed toward the third intracellular loop of the thromboxane receptor was able to immunoprecipitate native thromboxane receptor in solubilized membranes from human erythroleukemia cells and transfected cells.
Mol Pharmacol 1993 Nov
PMID:Point mutation in the seventh hydrophobic domain of the human thromboxane A2 receptor allows discrimination between agonist and antagonist binding sites. 824 16

There have been conflicting reports regarding the association of cytomegalovirus (CMV) and recurrent spontaneous abortions. It is difficult to assess the role of CMV in the endometrium by histology alone, since the characteristic cytomegalic virocytes are often scarce or absent in this site. Our purpose was to use the polymerase chain reaction (PCR) to detect cytomegalovirus in gestational tissue of women with recurrent spontaneous abortions. DNA was extracted from 25 samples of paraffin-embedded, formalin-fixed gestational tissue from 21 women with at least three unexplained spontaneous abortions (mean, 3.4). DNA from an unstained paraffin section of each specimen was amplified using nested, multiplex PCR specific for the late antigen and the major immediate early genes of CMV. The assay used has a demonstrated level of sensitivity on the order of 10(-2) virocytes per square centimeter of 4-microM paraffin section. Intact DNA was successfully isolated from 21 specimens in 18 patients. Histologic features of CMV infection were completely absent from these cases, and none of these specimens contained evidence of cytomegalovirus DNA. These findings suggest that CMV infection of gestational tissue is not a common direct cause of recurrent spontaneous abortions.
Diagn Mol Pathol 1993 Jun
PMID:Absence of cytomegalovirus in gestational tissue in recurrent spontaneous abortion. 826 75

The purpose of this study was to determine the occurrence and histologic correlates of viral infections in immunocompromised patients with pneumonia. Of the 44 immunocompromised patients studied, 37 had AIDS. Lung tissue from these patients, including 34 with pneumocystis pneumonia, was evaluated by in situ hybridization for the presence of cytomegalovirus (CMV), adenovirus, Epstein-Barr virus, and herpes simplex virus. Fifteen of the 44 patients were positive for at least one virus (34%); CMV (13 cases) was the most common. In an additional seven cases, CMV DNA was detected using the polymerase chain reaction (PCR), for an overall viral detection rate of 22 of 44 (50%). Histologic features were diagnostic of a viral infection in nine of 15 cases (60%) of the in situ positive cases and in nine of 22 (41%) of the tissues where viral DNA was detected by PCR. Mortality rate was significantly correlated with viral detection: 77% for the viral-positive cases and 27% for the viral-negative cases (p < 0.05). We concluded that in immunocompromised patients with pneumonitis, the detection of viral DNA is strongly correlated with survival and that histologic features of the inflamed lung tissue are a specific but insensitive means of diagnosing viral presence.
Diagn Mol Pathol 1993 Sep
PMID:Correlation of viral infection, histology, and mortality in immunocompromised patients with pneumonia. Analysis by in situ hybridization and the polymerase chain reaction. 828 33


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