Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Previous data indicated that Epstein-Barr virus DNA is terminated at both ends by direct or inverted repeats of from 1 to 12 copies of a 3 X 10(5)-dalton sequence. Thus, restriction endonuclease fragments which include either terminus vary in size by 3 X 10(5)-dalton increments (D. Given and E. Kieff, J. Virol. 28:524--542, 1978; S. D. Hayward and E. Kieff, J. Virol. 23:421--429, 1977). Furthermore, defined fragments containing either terminus hybridize to each other (Given and Kieff, J. Virol. 28:524--542, 1978). The 5' ends of the DNA are susceptible to lambda exonuclease digestion (Hayward and Kieff, J. Virol. 23:421--429, 1977). To determine whether the terminal DNA is a direct or inverted repeat, the structures formed after denaturation and reannealing of the DNA from one terminus and after annealing of lambda exonuclease-treated DNA were examined in the electron microscope. The data were as follows. (i) No inverted repeats were detected within the SalI D or EcoRI D terminal fragments of Epstein-Barr virus DNA. The absence of "hairpin- or pan-handle-like" structures in denatured and partially reannealed preparations of the SalI D or EcoRI D fragment and the absence of repetitive hairpin- or pan-handle-like structures in the free 5' tails of DNA treated with lambda exonuclease indicate that there is no inverted repeat within the 3 X 10(5)-dalton terminal reiteration. (ii) Denatured SalI D or EcoRI D fragments reanneal to form circles ranging in size from 3 X 10(5) to 2.5 X 1O(6) daltons, indicating the presence of multiple direct repeats within this terminus. (iii) Lambda exonuclease treatment of the DNA extracted from virus that had accumulated in the extracellular fluid resulted in asynchronous digestion of ends and extensive internal digestion, probably a consequence of nicks and gaps in the DNA. Most full-length molecules, after 5 min of lambda exonuclease digestion, annealed to form circles, indicating that there exists a direct repeat at both ends of the DNA. (iv) The finding of several circularized molecules with small, largely double-strand circles at the juncture of the ends indicates that the direct repeat at both ends is directly repeated within each end. Hybridization between the direct repeats at the termini is likely to be the mechanism by which Epstein-Barr virus DNA circularizes within infected cells (T. Lindahl, A. Adams, G. Bjursell, G. W. Bornkamm, C. Kaschka-Dierich, and U. Jehn, J. Mol. Biol. 102:511-530, 1976).
 ...
PMID:DNA of Epstein-Barr virus. V. Direct repeats of the ends of Epstein-Barr virus DNA. 22 46

Regulation of replicative functions in the Epstein-Barr virus (EBV) genome is mediated through activation of a virally encoded transcription factor, Z (BZLF1). We have shown that the Z gene product, which binds to AP-1 sites as a homodimer and has sequence similarity to c-Fos, can efficiently activate the EBV early promoter, BMRF1, in certain cell types (i.e., HeLa cells) but not others (i.e., Jurkat cells). Here we demonstrate that the c-myb proto-oncogene product, which is itself a DNA-binding protein and transcriptional transactivator, can interact synergistically with Z in activating the BMRF1 promoter in Jurkat cells (a T-cell line) or Raji cells (an EBV-positive B-cell), whereas the c-myb gene product by itself has little effect. The simian virus 40 early promoter is also synergistically activated by the Z/c-myb combination. Synergistic transactivation of the BMRF1 promoter by the Z/c-myb combination appears to involve direct binding by the Z protein but not the c-myb protein. A 30-bp sequence in the BMRF1 promoter which contains a Z binding site (a consensus AP-1 site) is sufficient to transfer high-level lymphoid-specific responsiveness to the Z/c-myb combination to a heterologous promoter. That the c-myb oncogene product can interact synergistically with an EBV-encoded member of the leucine zipper protein family suggests c-myb is likely to engage in similar interactions with cellularly encoded transcription factors.
Mol Cell Biol 1992 Jan
PMID:The cellular oncogene c-myb can interact synergistically with the Epstein-Barr virus BZLF1 transactivator in lymphoid cells. 130 87

In this study we addressed the question as to whether the mutagenesis by methylating agents is affected by the transcriptional activity of the damaged gene. An Epstein-Barr virus (EBV)-derived shuttle vector system was developed where the genetic target for mutation analysis, the bacterial gpt gene, is under the control of an eukaryotic inducible promoter in plasmid pF1-EBV and lacks the eukaryotic promoter in plasmid pF2-EBV. Two human cell lines that episomically maintain these shuttle vectors were established. In clone 6NT cells, which contain pF1-EBV plasmid, the gpt gene is actively transcribed and the transcription rate is regulated by zinc ions. In clone 3 cells, which harbor pF2-EBV plasmid, the gpt gene is not transcribed. Following treatment of both cell lines with the potent alkylating carcinogen N-methyl-N-nitrosourea (MNU), G.C to A.T transitions were the major mutagenic event, consistent with the miscoding potential of O6-methylguanine. The mutations were predominantly generated in the non-transcribed DNA strand of the active gpt gene. The same strand-bias was observed when the gpt gene was transcriptionally inactive, indicating that MNU-induced strand-specific formation of mutations is not due to transcription. Our data identify as major determinants of this phenomenon the sequence-specificity of MNU mutagenesis and the conformational properties of the target protein. Differences in mutation distribution were observed between the transcriptionally active and inactive gpt gene. This finding suggests that the organization of active genes in chromatin might modulate DNA alkylation and/or DNA repair.
J Mol Biol 1992 Feb 05
PMID:N-methyl-N-nitrosourea-induced mutations in human cells. Effects of the transcriptional activity of the target gene. 150 35

An in vitro model, called the Membrane Invasion Culture System (MICS), was used to study the invasive potential of an Epstein-Barr virus (EBV) positive lymphoblastoid cell line (LCL), an EBV-negative Burkitt lymphoma (BL) cell line of American origin and an EBV-positive BL of African origin. MICS measured the ability of these cell lines to invade reconstituted basement membrane-coated filters, which correlated with their tumorigenic and metastatic capabilities in a SCID mouse model. Furthermore, the significantly greater invasive behaviour of the EBV-positive LCL was directly correlated with the cells' ability to express and secrete human type IV collagenase (72 kDa), an important metalloproteinase responsible for the degradation of collagen IV in basement membranes. The data suggest that MICS and the SCID mouse are useful tests of tumorigenicity in lymphoid cells, with measurable effects in both systems related to human type IV collagenase activity. Both models allow further exploration of malignant phenotypes associated with EBV transformation of lymphoid tissues.
Mol Cell Probes 1992 Feb
PMID:Expression of type IV collagenase correlates with the invasion of human lymphoblastoid cell lines and pathogenesis in SCID mice. 131 23

Three distinct transcripts encoding two phosphatidylinositol (PI) linked isoforms of the neural cell adhesion molecule (NCAM) are induced during the differentiation of C2C12 myoblasts into myotubes. Corresponding NCAM clones were isolated from a mouse muscle cDNA library made in an Epstein-Barr virus shuttle vector that replicates extrachromosomally in human cells. Following transfection with the library, human cells expressing mouse NCAM were enriched using the fluorescence-activated cell sorter. Episomal NCAM clones recovered from sorted cells contain an 18-bp insert between exons 12 and 13. Two other NCAM cDNAs encode identical polypeptides containing a 108-bp insert homologous to the complete MSD1 domain, but differ in their 3' untranslated regions. Induction of MSD1-containing transcripts in advance of myotube formation suggests that muscle-specific NCAMs contribute to myogenesis from the earliest stages of differentiation. Moreover, our studies demonstrate the feasibility of cloning tissue-specific molecules by transfection and expression of cDNA libraries in episomal vectors.
Somat Cell Mol Genet 1992 Mar
PMID:Cloning muscle isoforms of neural cell adhesion molecule using an episomal shuttle vector. 131 56

Epstein-Barr virus/C3d receptor (CR2) is a glycoprotein of mol. wt 140,000 expressed on the surface of Raji cells. We previously isolated phosphorylated CR2 from purified Raji cell nuclei. We have analyzed the nuclear localization of CR2 by electron microscope immunochemistry of thin sections of Raji cells and we have compared the binding properties of CR2 expressed on purified plasma membranes or nuclei. Anti-CR2 mAb immunogold labeling of thin sections of Raji cells identified CR2 at the nuclear surface and also within the nucleus. Nuclear envelope associated CR2 was localized mainly at nuclear pores. Within the nucleus, CR2 was associated with ribonucleoprotein (RNP) interchromatin fibrils. This labeling was preserved in nuclear matrix preparations. CR2 expressed on the surfaces of purified nuclei or on the cell surface interacted with soluble and particle-bound C3bi/C3d. Monoclonal anti-CR2 antibodies, which recognized extracellular domains of CR2, reacted differently with CR2 depending on its subcellular localization. The presence of CR2 in nuclei may be due to translocation of the cell surface CR2 and/or the presence of two distinct intracellular pathways for mature CR2.
Mol Immunol 1992 Sep
PMID:Nuclear localization of the Epstein-Barr virus/C3d receptor (CR2) in the human Burkitt B lymphoma cell, Raji. 132 59

Polymerase chain reaction (PCR) was prospectively performed with cerebrospinal fluid (CSF) from 51 patients whose CSF was available for analysis and was submitted for viral culture and/or herpes simplex virus (HSV) serology and 20 patients whose CSF was submitted exclusively to the Clinical Biochemistry Laboratory. Primers were used that flanked a 92 bp segment of the HSV DNA polymerase gene (35 cycles). Amplified products were electrophoresed on agarose gel, blotted onto nylon membrane, and probed with a 32P-labelled sequence internal to the primers. For nested PCR, 1 microliter of PCR product was amplified for an additional 35 cycles before electrophoresis and Southern blot analysis. Review of the clinical records revealed that 15 patients had central nervous system (CNS) infections. Specific HSV DNA sequences were detected in CSF specimens of three of the individuals [PCR(2), nested PCR(1)]. Two of these patients had disseminated HSV infection including encephalitis and one patient had aseptic meningitis. The diagnoses of the 12 patients with CNS infection who did not have HSV DNA detected in CSF included encephalitis [varicella-zoster virus (1), cytomegalovirus (1), Mycoplasma pneumoniae (1)], meningitis [Neisseria meningitidis (1), Coccidioides immitis (1), Enterovirus (1), aseptic meningitis (1)], varicella-zoster radiculitis (2), human immunodeficiency virus dementia (2), and transverse myelitis due to Epstein-Barr virus (1). Importantly, HSV DNA was also not detected in the CSF of the 36 patients who did not have CNS infection and 20 samples submitted exclusively to the Clinical Biochemistry Laboratory. Our findings demonstrate the utility of PCR as a rapid, non-invasive method for the routine laboratory diagnosis of CNS infection due to HSV.
Mol Cell Probes 1992 Oct
PMID:A prospective study of the polymerase chain reaction for detection of herpes simplex virus in cerebrospinal fluid submitted to the clinical virology laboratory. 133 47

The Epstein-Barr virus (EBV) is associated with undifferentiated nasopharyngeal carcinomas (NPCs). Recently, EBV DNA has been demonstrated also in some cases of gastric carcinoma with similar morphology as undifferentiated NPC. Here we report on the expression of EBV genes in a gastric undifferentiated carcinoma of nasopharyngeal type (UCNT). The small EBV-encoded nuclear RNAs, EBERs, were expressed in all tumor cells. The BZLF1 transactivator protein, which disrupts viral latency, was detectable in a small subset of tumor cells. The latent membrane protein and the nuclear antigen EBNA2 were not expressed. These results indicate that lytic EBV infection may be possible in undifferentiated epithelial cells. Our findings add to the growing body of evidence suggesting a strong association of gastric UCNT with EBV and point to the possibility of an involvement of the virus in the pathogenesis of this neoplasm.
Diagn Mol Pathol 1992 Jun
PMID:Epstein-Barr virus and carcinomas. Expression of the viral genome in an undifferentiated gastric carcinoma. 134 57

The authors describe a highly sensitive and practical in situ hybridization method using an oligonucleotide probe for EBER1 RNA for the detection of Epstein-Barr virus (EBV) in formalin-fixed, paraffin-embedded tissue sections. Paraffin-embedded tissues from 793 cases of normal and neoplastic tissues were studied. Nuclear staining for EBV RNA was uniformly present in all or virtually all neoplastic cells in a variety of known EBV-positive tumors. We also demonstrate rare EBV-infected cells in normal lymphoid tissues. RNAase predigestion, competitive inhibition, and control probe studies confirmed the specificity of the staining. In addition, cross-reactivity of EBV RNA staining with other viruses was not present. Additionally, the distribution of EBV in a wide variety of other normal and neoplastic tissues is reported.
Diagn Mol Pathol 1992 Dec
PMID:Description of an in situ hybridization methodology for detection of Epstein-Barr virus RNA in paraffin-embedded tissues, with a survey of normal and neoplastic tissues. 134 73

The Epstein-Barr virus (EBV)-encoded membrane protein, LMP, is expressed in a proportion of undifferentiated nasopharyngeal carcinomas (NPC). Previous studies have shown that the transfection of the gene encoding LMP into a human keratinocyte line, RHEK-1, induces morphological alterations and a reduced expression of cytokeratins. We have analyzed immunophenotypic changes in the RHEK-1 line following LMP-transfection and compared these changes with the phenotype of NPC biopsies. We demonstrate a downregulation of two epithelial markers, an epithelial glycoprotein (EGP) defined by the monoclonal antibody Ber-EP4 and the epithelial membrane antigen (EMA). Furthermore, a lymphocyte activation-associated antigen, CDw70 antigen, which was absent from the parental line was expressed in virtually all LMP-transfected cells, whereas no similar effect was seen with respect to the CD30 activation antigen. Nine EBV-positive human NPCs, six of which were LMP-positive expressed the EGP and EMA. The CDw70 antigen, which is not normally present in epithelial cells, was expressed in eight biopsies, whereas the CD30 antigen was not detectable. Our findings are in keeping with the notion that LMP expression may contribute to the immunophenotype of human NPCs.
Virchows Arch B Cell Pathol Incl Mol Pathol 1992
PMID:The Epstein-Barr virus encoded membrane protein (LMP) induces phenotypic changes in epithelial cells. 135 76


1 2 3 4 5 6 7 8 9 10 Next >>