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

The nuclear transcription factor c-Myb, which is highly expressed in hematopoietic cells, has been shown to be functional in NIH 3T3 cells: cells that do not possess detectable levels of c-Myb. To identify endogenous target genes of c-Myb in fibroblasts, RNA isolated from NIH 3T3 cells stably transfected with a full-length or a dominant negative c-myb construct (GREMyb and GREMEn, respectively) was subjected to differential display analysis. 5'-Rapid amplification of cDNA ends of a selected band, sequencing, and a nucleotide homology search led to the identification of thrombospondin 2 (TSP 2) as the gene product repressed in GREMyb and induced in GREMEn cells. The pattern of TSP 2 expression during the cell cycle was consistent with c-myb-dependent regulation. The possibility that the identified transcript was TSP 1, a homologous product known to be repressed by v-Src, c-Jun, and v-Myc, was ruled out by using a TSP 2-specific DNA probe and by showing a distinct pattern of regulation of TSP 1 and TSP 2 expression. Nuclear run-on and TSP 2 promoter-reporter (chloramphenicol acetyltransferase) assays showed similar transcriptional levels in GREMyb and NIH 3T3 cells. However, mRNA stability studies showed a much shorter TSP 2 mRNA half-life in GREMyb compared with wild type NIH 3T3 cells, suggesting that c-myb affects TSP 2 expression via a post-transcriptional mechanism. The implications of a protooncogene-mediated suppression of TSP expression are discussed.
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PMID:Myb-dependent regulation of thrombospondin 2 expression. Role of mRNA stability. 969 6

The preferential expression of the protooncogene c-myb in hematopoietic cells is in part regulated by a mechanism of transcriptional block in the first intron. By electrophoresis mobility shift assays using probes corresponding to different segments of the putative human c-myb intron 1 transcription pause region and nuclear extracts from myeloid leukemia HL 60 and fibroblast WI 38 cells, we detected a HL-60-specific DNA-protein complex with a 123-bp fragment containing binding sites for the interferon regulatory factors (IRFs) nuclear proteins. Formation of the DNA-protein complex was abrogated by competition with an oligomer containing the wild-type, but not the mutated, IRF binding site and the complex was specifically supershifted by the anti-IRF-1 or the anti-IRF-2 antibody. Moreover, in vitro translated IRF-1 or IRF-2 protein did interact with the 123-bp c-myb intron 1 fragment. Upon TPA-induced differentiation, c-myb expression was readily down-modulated in parental HL 60 cells, but not in cells transfected with an antisense IRF-1 plasmid. Moreover, chloramphenicol acetyltransferase activity driven by a c-myb promoter containing the entire intron 1 was suppressed upon IRF-1, but not IRF-2 expression. Together, these results are consistent with the existence of a functional relationship between IRF-1 and c-myb in which IRF-1 negatively regulates c-myb expression at the transcriptional level by a mechanism that may depend on the interaction of IRF-1 with a segment of the c-myb gene implicated in transcription pausing.
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PMID:The interferon regulatory factors 1 and 2 bind to a segment of the human c-myb first intron: possible role in the regulation of c-myb expression. 1073 71

We previously reported that expression of the T-cell receptor (TCR) alpha and lck genes is extinguished in hybrids between mouse T-lymphoma EL4 cells and mouse fibroblast B82 cells. In the present study, we found that the activities of the TCRalpha minimum enhancer and the lck promoter monitored by the luciferase or chloramphenicol acetyltransferase (CAT) assays were markedly inhibited in the hybrids. Expression of the TCF-1, LEF-1, GATA-3, Ikaros, c-myb and Fli-1 genes, which encode the haematopoietic cell-restricted transcription factors that appear to be responsible for the activities of the enhancer and the promoter, was fully extinguished or markedly suppressed in the hybrids. On the other hand, expression of the transcription factor genes observed in both parental cells, such as the AML1 and c-ets-1 genes, and that of the genes encoding ubiquitously expressed transcription factors, such as the E2A, CREB and c-ets-2 genes, was not significantly suppressed in the hybrids. These results suggest that the genes encoding haematopoietic cell-restricted transcription factors are targets for negative regulation in fibroblastic background and that the repression of these genes may consequently lead to suppression of the promoter and/or enhancer activities of several T-cell-specific structural genes in T-lymphoma x fibroblast cell hybrids.
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PMID:Extinction of expression of the genes encoding haematopoietic cell-restricted transcription factors in T-lymphoma x fibroblast cell hybrids. 1168 56


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