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

Transcription factor E2F binds to cellular promoters of certain growth- and cell cycle-controlling genes and forms distinct heteromeric complexes with other nuclear proteins. We show here that alpha and beta interferons (alpha, beta) and interleukin-6 abolished the E2F-containing DNA-binding complexes in Daudi Burkitt lymphoma cells and in M1 myeloblastic cells, which responded to the cytokines by suppression of c-myc transcription. Time kinetics studies showed that the abolishment of E2F complexes coincided with reduction of c-myc expression and that both molecular events preceded the cell cycle block in G0/G1 phase. In contrast, the pattern of E2F complexes remained unchanged in an interferon-treated growth-resistant Daudi cell mutant that displayed relaxed regulation of c-myc. All of the DNA-binding E2F complexes, including those containing the retinoblastoma protein (pRB), cyclin A-p33cdk2, and the free forms of E2F, were reduced by interferons or interleukin-6. Their abolishment was unperturbed by pharmacological treatments that alleviated the cyclin A and pRB responses to interferon. Thus, changes in cyclin A expression and pRB phosphorylation are not primary events that influence the pattern of E2F responses to cytokines. Addition of EDTA to cell extracts of interferon-treated Daudi cells restored the DNA-binding activity of E2F, resulting in the appearance of a single E2F complex that exclusively contained pRB. It is suggested that the regulation of E2F by growth-inhibitory cytokines that induce cell cycle exit takes place at the level of the DNA-binding activity, and by that mean it differs basically from the phase-specific regulation of E2F in cycling cells.
Mol Cell Biol 1993 Sep
PMID:Interferons and interleukin-6 suppress the DNA-binding activity of E2F in growth-sensitive hematopoietic cells. 768 48

A common feature of the Epstein-Barr virus (EBV)-associated malignancy, Burkitt's lymphoma, is chromosomal translocation affecting the c-myc oncogene. We report here that an EBV immediate-early (IE) protein, BRLF1 (R), transactivates the murine and human c-myc promoters. The R transactivator enhances expression from transiently transfected murine and human c-myc promoters as determined both at the CAT reporter and at the mRNA level. Transactivation of the human c-myc promoter by R occurs in several different cell lines, and this effect is reporter-gene independent. Both the P1 and P2 c-myc promoters can be activated by the EBV R IE protein, although the R-induced transactivation of P1 is greater than P2. The portion of the human c-myc promoter from -228 to -63 (relative to the P1 mRNA start site) is necessary, but not sufficient, for transactivation by R in the Louckes B-cell line. Binding of the R protein directly to the c-myc promoter could not be demonstrated, suggesting that the effect of R on c-myc activity occurs by an indirect mechanism. The ability of an EBV protein to activate c-myc expression is likely to facilitate productive viral infection and is also potentially relevant in the genesis of EBV-associated lymphomas.
Cell Mol Biol (Noisy-le-grand) 1994 Sep
PMID:The Epstein-Barr virus BRLF1 gene product transactivates the murine and human c-myc promoters. 781 82

The Burkitt's lymphoma receptor 1 (BLR1) identified initially in Burkitt lymphoma cells has been the first member of the superfamily of G-protein-coupled receptors with a lymphocyte specific expression pattern. BLR1 shows significant relationship to receptors for chemokines (IL-8, MIP-1 beta) and neuropeptides. The gene encoding the murine homologue of the human BLR1 receptor was isolated and used to study its tissue-specific expression. Blr-1 consists of two exons encoding a protein of 374 amino acid residues which shows 83% identity with the human homologue. Screening of normal tissues of adult BALB/c mice revealed that blr-1-specific RNA is detected consistently at low levels in secondary lymphatic organs. The blr-1 gene is expressed regularly and strongly in lymphomas of mature B cells but not in plasmacytomas. SCID mice deficient in the development of mature B cells have strongly reduced levels of blr-1-specific RNA in the spleen. Cytokine mediated induction (IL4, IL6) of terminal differentiation of resting B cells towards Ig-secreting plasma cells completely downregulates expression of blr-1. RNA in situ hybridization using brain sections demonstrates blr 1 transcription in the granule and Purkinje cell layer of the cerebellum. The precise delineation of the restricted expression pattern of the blr-1 gene will support the identification of its ligand and may provide a clue to understand how BLR1 exerts its biological function within the immune and nervous system.
Cell Mol Biol (Noisy-le-grand) 1994 May
PMID:Selective expression of the murine homologue of the G-protein-coupled receptor BLR1 in B cell differentiation, B cell neoplasia and defined areas of the cerebellum. 792 Jan 82

Elevated levels of mutant forms of the p53 tumor suppressor are a hallmark of many transformed cells. Multiple mechanisms such as increased stability of the protein and increased transcription of the gene can account for elevated p53 expression. Recent findings indicate that c-Myc/Max heterodimers can bind to an essential CA(C/T)GTG-containing site in the p53 promoter and elevate its expression. We have addressed the possibility that elevated mutant p53 expression is due to deregulated c-Myc expression. Here we demonstrate that the human p53 promoter is transactivated by high c-Myc expression and repressed by high Max expression. In examining the relative levels of c-Myc and p53 in human Burkitt's lymphomas and other B-lymphoid lines, we found that there is a correlation between the levels of c-Myc protein and p53 mRNA expression. In particular, cells that express very low levels of c-Myc protein also express low levels of p53 mRNA, while cells that express high levels of c-Myc tend to express high levels of p53 mRNA. To determine whether the p53 gene can be a target for c-Myc in vivo, we assayed the effects of antisense c-myc RNA on the levels of endogenous p53 mRNA. The results indicate that the presence of antisense c-myc RNA leads to a reduction in the levels of c-Myc protein, p53 mRNA, and expression from the p53 promoter. Taken together, our findings support a direct role for c-Myc in elevating expression of the mutant p53 gene in some tumors.
Mol Cell Biol 1994 Dec
PMID:Transactivation of the human p53 tumor suppressor gene by c-Myc/Max contributes to elevated mutant p53 expression in some tumors. 796 21

An in vivo footprint over a potential NF-kappa B site in the first exon of the c-myc gene has been identified on the translocated allele in the Ramos Burkitt's lymphoma cell line. The potential NF-kappa B site in the 5' flanking sequence of c-myc was found to be occupied on the translocated allele in the Raji Burkitt's cell line. Electrophoretic mobility shift assays with each of these sequences demonstrated complexes with mobilities identical to those of the NF-kappa B site from the kappa light-chain gene. A supershift was obtained with anti-p50 antibody with the exon site. The upstream-site shift complex disappeared with the addition of anti-p50 antibody. Binding of NF-kappa B proteins to the c-myc exon and upstream sites was demonstrated by induction of binding upon differentiation of pre-B 70Z/3 cells to B cells. UV cross-linking experiments revealed that a protein with a molecular mass of 50 kDa bound to the exon and upstream sites. Transfection experiments with Raji cells demonstrated that both sites functioned as positive regulatory regions, with a drop in activity level when either site was mutated. Access to these sites is blocked in the silent normal c-myc allele in Burkitt's lymphoma cells, while Rel family proteins bind to these sites in the translocated allele. We conclude that the two NF-kappa B sites function as positive regulatory regions for the translocated c-myc gene in Burkitt's lymphoma.
Mol Cell Biol 1994 Dec
PMID:NF-kappa B sites function as positive regulators of expression of the translocated c-myc allele in Burkitt's lymphoma. 796 36

Antisense RNA transcription of human c-myc gene has been examined in HeLa, Burkitt lymphoma BL-60 t(8;22) cells, and diploid fibroblasts. By means of the primer extension technique two startpoints of antisense transcription have been detected and mapped with the first (untranslated) exon of the c-myc gene. Similarity between the antisense nucleotide sequence of the first c-myc intron and the SV40 DNA fragment containing the binding sites for transcriptions factors GT-I, GT-II, TC-I, and TC-II has been revealed by computer analysis. It has been established that the DNA fragment of the first c-myc intron is able to form complexes with proteins from the HeLa cell extract. Three nucleotide sequences (TTTCTG, TTTTTA, and TGACTTGTC) are involved in the reactions. These data imply that the c-myc antisense transcripts might take part in the regulation of human c-myc gene expression.
Mol Biol (Mosk)
PMID:[Transcription of antisense RNA for the human c-myc gene]. 799 Aug 19

The proto-oncogene bmi-1 is frequently activated by Moloney murine leukemia proviral insertions in E mu-myc transgenic mice1,2. Using a mouse bmi-1 cDNA probe a transcript of 3.3 kb was detected on Northern blots of human Burkitt's lymphoma cell lines. We have isolated and sequenced cDNA clones from a human erythroleukemia cell line (K562) derived cDNA library, using different mouse bmi-1 cDNA fragments as a probe. Analysis of genomic BMI-1 sequences reveals a gene structure which is very similar to that of the mouse, consisting of at least 10 exons. The human cDNA is 3203 bp in length and shows 86% identity to the mouse nucleotide sequence. The open reading frame encodes a protein of 326 amino acids which shares 98% identity to the amino acid sequence of mouse bmi-1 protein. In vitro translation experiments show that human cDNA derived RNA translates into a protein with a mobility of 44-46 kD on SDS polyacrylamide gels. Fluorescence in situ hybridization (FISH) on metaphase chromosome spreads located the human BMI-1 gene to the short arm of chromosome 10 (10p13), a region known to be involved in translocations in various leukemias.
Hum Mol Genet 1993 Oct
PMID:Characterization and chromosomal localization of the human proto-oncogene BMI-1. 826 12

The lymphocytes of one HLA-A11 positive individual (A1, A11, B49, B55) were stimulated in vitro with the autologous EBV transformed lymphoblastoid cell line (LCL). The culture contained HLA-A1, A11 and B55 restricted, LCL selective cytotoxic T cells (CTLs). In the T cell culture stimulated four times, the lysis of A11 and B55 carrying targets suggested that the subsets of the two latter CTL types had similar size. After further stimulations the B55 restricted CTLs were enriched in the culture. Earlier results suggested that in HLA-A11 positive individuals the A11-restricted LCL-selective CTL subset dominates. The sensitivity of a target panel including Burkitt lymphoma (BL) lines suggested that the peptide presented by the B55 molecule differs in A and B type EBV strain carrying cells.
Mol Immunol 1994 Jan
PMID:Generation of HLA-B55 restricted T lymphocyte mediated cytotoxicity against autologous LCL. 830 99

UV radiation is known to induce lymphocyte nonresponsiveness both in vitro and in vivo. We have found that UV radiation rapidly induced tyrosine phosphorylation and calcium signaling in normal human peripheral blood lymphocytes. In the leukemic T cell line Jurkat and the Burkitt's lymphoma cell line Ramos, UV rapidly induced tyrosine phosphorylation in a wavelength-dependent manner, giving strong signals after UVB and UVC, but not UVA, irradiation. Similarly, in Jurkat cells UV-induced calcium signals were dependent on the dose of UVB or UVC irradiation over a range of 150-1200 J/m2, but only a small signal was observed for UVA at a dose of 1200 J/m2. The UV-induced calcium signals were blocked by the tyrosine kinase inhibitor herbimycin A, indicating that they were dependent on tyrosine phosphorylation. Phospholipase C (PLC) gamma 1 was tyrosine phosphorylated in response to UV irradiation but to a lesser extent than observed after CD3 cross-linking. However, PLC gamma 1-associated proteins demonstrated to bind to the PLC gamma 1 SH2 domain were tyrosine phosphorylated strongly after UV irradiation. A similar dose response was observed for the inhibition by herbimycin A of UV-induced calcium signals and UV-induced tyrosine phosphorylation of PLC gamma 1 and associated proteins. We propose that in contrast to CD3/Ti stimulation, UV aberrantly triggers lymphocyte signal transduction pathways by a mechanism that bypasses normal receptor control.
Mol Biol Cell 1993 May
PMID:Ultraviolet radiation rapidly induces tyrosine phosphorylation and calcium signaling in lymphocytes. 833 6

Transcription of the human proto-oncogene c-myc is governed by two tandem principal promoters, termed P1 and P2. In general, the downstream promoter, P2, is predominant, which is in contrast to the promoter occlusion phenomenon usually observed in genes containing tandem promoters. A shift in human c-myc promoter usage has been observed in some tumor cells and in certain physiological conditions. However, the mechanisms that regulate promoter usage are not well understood. The present studies identify regulators which are required to promote transcription from both human c-myc promoters, P1 and P2, and have a role in determining their relative activities in vivo. A novel regulatory region located 101 bp upstream of P1 was characterized and contains five tandem repeats of the consensus sequence CCCTCCCC (CT element). The integrity of the region containing all five elements is required to promote transcription from P1 and for maximal activity from P2 in vivo. A single copy of this same element, designated CT-I2, also appears in an inverted orientation 53 bp upstream of the P2 transcription start site. This element has an inhibitory effect on P1 transcription and is required for P2 transcription. The transcription factor Sp1 was identified as the factor that binds specifically to the tandem CT elements upstream of P1 and to the CT-I2 element upstream of P2. In addition, the recently cloned zinc finger protein ZF87, or MAZ, was also able to bind these same elements in vitro. The five tandem CT elements can be functionally replaced by a heterologous enhancer that only in the absence of CT-I2 reverses the promoter usage, similar to what is observed in the translocated c-myc allele of Burkitt's lymphoma cells.
Mol Cell Biol 1993 Sep
PMID:Repeated CT elements bound by zinc finger proteins control the absolute and relative activities of the two principal human c-myc promoters. 835 12


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