Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.3.1.28 (chloramphenicol acetyltransferase)
 5,100 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Transfection of a plasmid encoding the Epstein-Barr virus (EBV) nuclear antigen 2 (EBNA2) gene confers resistance to the antiproliferative effect of alpha interferon (IFN-alpha) in EBV-negative U968 cells (P. Aman and A. von Gabain, EMBO J. 9:147-152, 1990). We studied the expression of IFN-stimulated genes (ISGs) in two pairs of Burkitt's lymphoma cell lines, differing in the expression of the putative immortalizing gene of EBV, EBNA2. In EBNA2-expressing cells, the induction of four ISGs by IFN-alpha was strongly reduced or, in some cases, abolished. Chloramphenicol acetyltransferase reporter gene constructs containing different IFN-stimulated response elements were transfected into EBNA2-negative and EBNA2-positive cells. Induction of chloramphenicol acetyltransferase activity by IFN was impaired in EBNA2-positive cells. Also, a reporter gene construct driven by an IFN-gamma-sensitive promoter element was affected. However, as revealed by gel shift assays, EBNA2-positive and EBNA2-negative cells exhibited a nearly identical pattern of IFN-stimulated response element-binding proteins. Most important, activation of the factor ISGF-3, which previously has been shown to be required and sufficient for transcriptional activation of IFN-induced genes, was not inhibited in IFN-resistant cells expressing EBNA2. The mechanism of the EBNA2-related IFN resistance seems to be distinct both from the resistance mediated by hepatitis virus and adenovirus gene products and from the IFN resistance in Daudi cell variants. In these three cases, the transcriptional block of IFN-induced genes is due to inhibition of ISGF-3 activation and binding. Our data suggest that the EBNA2-related IFN resistance in Burkitt's lymphoma cells acts downstream of the activation of ISGF-3.
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PMID:The EBNA2-related resistance towards alpha interferon (IFN-alpha) in Burkitt's lymphoma cells effects induction of IFN-induced genes but not the activation of transcription factor ISGF-3. 140 70

Treatment of Daudi or HeLa cells with human interferon (IFN) alpha 8 before induction with either poly(I)-poly(C) or Sendai virus resulted in an 8- to 100-fold increase in IFN production. The extent of priming in Daudi cells paralleled the increase in the intracellular content of IFN-beta mRNA. IFN-alpha mRNA remained undetectable in poly(I)-poly(C)-treated Daudi cells either before or after priming. An IFN-resistant clone of Daudi cells was found to produce 4- to 20-fold more IFN after priming, indicating that priming was unrelated to the phenotype of IFN sensitivity. IFN treatment of either Daudi or HeLa cells transfected with the human IFN-beta promoter (-282 to -37) linked to the chloramphenicol acetyltransferase (CAT) gene resulted in an increase in CAT activity after induction with poly(I)-poly(C) or Sendai virus. A synthetic double-stranded oligonucleotide corresponding to an authentic 30-base-pair (bp) region of the human IFN-beta promoter between positions -91 and -62 was found to confer virus inducibility upon the reporter CAT gene in HeLa cells. IFN treatment of HeLa cells transfected with this 30-bp region of the IFN-beta promoter in either the correct or reversed orientation also increased CAT activity upon subsequent induction. IFN treatment alone had no detectable effect on the activity of either the 30-bp region or the complete human IFN promoter.
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PMID:Priming affects the activity of a specific region of the promoter of the human beta interferon gene. 215 28

Several lines of evidence are compatible with the hypothesis that Epstein-Barr virus (EBV) nuclear antigen 2 (EBNA-2) or leader protein (EBNA-LP) affects expression of the EBV latent infection membrane protein LMP1. We now demonstrate the following. (i) Acute transfection and expression of EBNA-2 under control of simian virus 40 or Moloney murine leukemia virus promoters resulted in increased LMP1 expression in P3HR-1-infected Burkitt's lymphoma cells and the P3HR-1 or Daudi cell line. (ii) Transfection and expression of EBNA-LP alone had no effect on LMP1 expression and did not act synergistically with EBNA-2 to affect LMP1 expression. (iii) LMP1 expression in Daudi and P3HR-1-infected cells was controlled at the mRNA level, and EBNA-2 expression in Daudi cells increased LMP1 mRNA. (iv) No other EBV genes were required for EBNA-2 transactivation of LMP1 since cotransfection of recombinant EBNA-2 expression vectors and genomic LMP1 DNA fragments enhanced LMP1 expression in the EBV-negative B-lymphoma cell lines BJAB, Louckes, and BL30. (v) An EBNA-2-responsive element was found within the -512 to +40 LMP1 DNA since this DNA linked to a chloramphenicol acetyltransferase reporter gene was transactivated by cotransfection with an EBNA-2 expression vector. (vi) The EBV type 2 EBNA-2 transactivated LMP1 as well as the EBV type 1 EBNA-2. (vii) Two deletions within the EBNA-2 gene which rendered EBV transformation incompetent did not transactivate LMP1, whereas a transformation-competent EBNA-2 deletion mutant did transactivate LMP1. LMP1 is a potent effector of B-lymphocyte activation and can act synergistically with EBNA-2 to induce cellular CD23 gene expression. Thus, EBNA-2 transactivation of LMP1 amplifies the biological impact of EBNA-2 and underscores its central role in EBV-induced growth transformation.
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PMID:Epstein-Barr virus nuclear antigen 2 transactivates latent membrane protein LMP1. 235 28

The p53 is a nuclear protein that is associated with normal cellular proliferation and can cooperate with Ha-ras in causing cellular transformation in vitro. Lineage association is known to exist between p53 expression and normal lymphopoiesis, but not myelopoiesis. We studied the expression of p53 using chronic myelogenous leukemia (CML) cell lines, somatic hybrids of these cells, and leukemic cells from CML patients. Lymphoid CML lines expressed both p53 mRNA and protein. We also analyzed p53 synthesis by two B-lymphoid lines from the same CML patient; cells of one line were derived from the neoplastic clone, cells of the other were derived from the normal clone. Both synthesized equal amounts of a phosphorylated p53 protein. None of the myeloid CML lines expressed detectable p53 protein and two of four expressed negligible p53 mRNA. Two other myeloid CML lines and myeloid cells from three of four patients expressed p53 mRNA. These findings suggest that expression of the gene is not regulated normally in CML. Several approaches were pursued to explore the differential expression of p53. Southern blot analyses showed no gross alterations in the p53 gene from cells of either the expressing or the nonexpressing lines. No difference in the pattern of demethylated CpG sites was noted in the region of the p53 gene in cells from K562 (myeloid p53 nonexpressor) and in BV173 (lymphoid p53 expressor). The sites of demethylation clustered in and around the p53 promoter in both cell lines. Somatic hybrids formed between a p53 mRNA nonexpressor myeloid line (K562) and the parental p53 expressor lymphoid lines (Daudi, PUT) produced p53 mRNA and protein, suggesting that p53 is a dominantly expressed protein and that lack of expression in myeloid cells is not mediated by a trans-acting negative regulatory protein. DNA transfection experiments performed using the indicator gene chloramphenicol acetyltransferase attached to promoter sequences of p53 showed that these constructs were equally activated in BV173 (p53 expressor) and K562 (p53 mRNA nonexpressor). The mechanism of p53 regulation in CML remains unclear.
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PMID:p53 in chronic myelogenous leukemia. Study of mechanisms of differential expression. 328 Jul 26

E2F is a heterodimeric transcription factor that controls transcription of several growth-regulatory genes including cdc2. To investigate the mechanism of interferon-alpha (IFN-alpha)-mediated growth suppression of hematopoietic cells, we examined the effect of IFN-alpha on the expression and function of E2F using IFN-sensitive Daudi cells. Down-regulation of E2F-1, a subunit of E2F, was observed after 8 h of culture with IFN-alpha; expression of E2F-4, another subunit of E2F, and DP-1, a heterodimeric partner of E2F, was unaffected. Gel shift assays revealed that the DNA binding activity of free E2F, which is composed of E2F-1 and E2F-4, was inhibited by IFN-alpha. In contrast, IFN-alpha did not affect the DNA binding ability of E2F-1 and E2F-4 in a complex with retinoblastoma (RB) susceptibility gene family proteins including pRB, p107, and p130. IFN-alpha could induce dephosphorylation of pRB, thereby turning active E2F-pRB complexes into transcriptional repressors. Transient chloramphenicol acetyltransferase assays revealed that the activity of the E2F-dependent cdc2 promoter was suppressed by IFN-alpha. These results suggest that the antiproliferative action of IFN-alpha is mediated through the modulation of E2F activity in two different ways: down-regulation of transcriptionally active free E2F and conversion of E2F-pRB complexes into transcriptional repressors.
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PMID:Modulation of E2F activity is linked to interferon-induced growth suppression of hematopoietic cells. 913 87

Interleukin-12 is produced in response to infection with bacteria or parasites or to bacterial constituents such as LPS in monocytes/macrophages and dendritic cells, and also generated by the interaction between activated T cells and antigen-presenting cells via CD40-CD40 ligand (CD40L). So far, transcriptional analyses of p40 have been carried out only using bacterial constituents such as LPS as stimuli. In the present study, we have characterized the transcriptional induction of p40 by CD40 ligation in a human B lymphoblastoid cell line, Daudi, and a human acute monocytic leukemia cell line, THP-1. These cells, stimulated by an agonistic monoclonal antibody against CD40 or by transfection with a CD40L expression vector, secreted p40 and showed enhanced p40 mRNA expression. Sequence analysis of the p40 promoter region identified two potential nuclear factor (NF)-kappaB binding sites conserved between mouse and human. Electrophoretic mobility shift assay revealed that the potential NF-kappaB binding sequence which is located around 120 bp upstream of the transcription initiation site in murine and human p40 genes formed an NF-kappaB complex with nuclear extract from Daudi cells stimulated by CD40 ligation. Moreover, transfection of Daudi cells with the polymerized NF-kappaB binding sequence ligated to a thymidine kinase/chloramphenicol acetyltransferase (CAT) reporter plasmid greatly induced CAT activity, but transfection with the polymerized mutated NF-kappaB binding sequence did not. These results suggest that the NF-kappaB binding site located around 120 bp upstream of the transcription initiation site in murine and human p40 promoter regions could be important for the p40 induction by CD40 ligation via activation of NF-kappaB.
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PMID:Induction of interleukin-12 p40 transcript by CD40 ligation via activation of nuclear factor-kappaB. 946 36