Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.1.30.1 (S1 nuclease)
3,660 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Transcription of the c-myc gene is initiated mainly from two promoters, P1 and P2. By S1 nuclease analysis we found that there is 8 times more P2- than P1-initiated RNA in total RNA from HL60 cells. The half-lives of P1- and P2-initiated transcripts are 26 and 18 min, respectively, so the difference in the relative abundance of the mRNAs is not due to differences in their stabilities. The relative rates of transcription from the P1 and P2 promoters, estimated by in vitro nuclear run-on analysis, were found to differ by about 10-fold, sufficient to account for the difference in the steady-state levels of the two mRNAs. The abundance of c-myc mRNA changes dramatically during differentiation of HL60 cells. Dimethyl sulphoxide causes a very rapid reduction in total c-myc mRNA, while with phorbol ester a transient increase occurs followed by a more gradual decline. At no time during these dramatic alterations were significant changes detected in the relative abundance of P1- and P2-initiated mRNAs, or in their stabilities.
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PMID:Regulation of the relative abundances of c-myc mRNAs in human promyelocytic HL60 cells. 229 63

During post-natal cerebellar development the steady-state levels of c-myc transcripts exhibit characteristic changes. As determined by the S1 nuclease protection assay the level of c-myc transcript, which is very high in the late embryonic cerebellum, decreased to low levels shortly after birth. One week later there is a second period of c-myc mRNA accumulation followed by a marked decline to finally reach the low adult value. The second peak of high c-myc mRNA level correlates well with the proliferation of granule cell precursors, and it is characterized by a marked change in the ratio of the two types of transcripts started at the known c-myc promoters 1 and 2. This indicates a change in the cell population involved in the transcription of the c-myc gene. In situ hybridization shows transiently elevated c-myc mRNA levels in neurons of the cerebellar cortex. At post-natal days 3 and 10 (P3 and P10) c-myc transcripts are detectable in the superficial external granular layer composed primarily of mitotically active (neural precursor) cells. Purkinje cell somata show cytoplasmic label at P10. These large postmitotic neurons undergo rapid differentiation at this developmental stage. In the adult cerebellum the low c-myc mRNA level is apparently due to Purkinje cells with barely detectable amounts of c-myc transcripts. The vast majority of mature cerebellar neurons, the internal granule cells, have no specific hybridization signal for c-myc. We conclude that neurons in vivo can accumulate c-myc messenger during proliferation and/or differentiation, perhaps as a cellular response to an external signal.
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PMID:Proto-oncogene c-myc is expressed in cerebellar neurons at different developmental stages. 242 14

A tumorigenic human hepatoma cell line, Hep G2, has been shown to have high steady-state levels of c-myc transcripts compared to normal human liver. We have now characterized c-myc expression in Hep G2 cells with regard to message stability, gene rearrangements, gene amplification, chromosomal translocations, promoter utilization, and the effects of protein synthesis inhibitors. We have determined that the half-life of the Hep G2 c-myc transcript is approximately 20 min and conclude that the high steady-state level of c-myc mRNA is not the result of a specific stabilization of the c-myc message but probably results from increased c-myc gene transcription. c-myc expression in Hep G2 cells appears to be constitutive, since it remains constant in different cell growth states (log phase versus nondividing cells). The high constitutive expression of the c-myc gene in Hep G2 cells could not be explained by gene amplification, gene rearrangements, or chromosomal translocations. However, based on an S1 nuclease protection assay, the P1/P2 promoter utilization ratio is approximately 1/1 which differs from the 1/5 P1/P2 ratio observed in normal human liver. Treatment with cycloheximide, a protein synthesis inhibitor, does not superinduce Hep G2 c-myc transcription based on transcription "run on" and RNA slot blot analysis. However, cycloheximide treatment does exert a posttranscriptional effect involving the specific stabilization of the c-myc message.
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PMID:Analysis of c-myc expression in a human hepatoma cell line. 303 14

To gain further insight into the mechanism of age-associated loss of T cell proliferative responses to mitogenic lectins, we measured c-myc specific mRNA accumulation in Con A-stimulated cultures of spleen cells from old and young mice using Northern blot and S1 nuclease protection analyses. Aging led to a consistent decline (an average of approximately 60%) in the level of c-myc mRNA in stimulated cells. The time course for c-myc RNA accumulation was similar for old and young mice. Nuclear runoff experiments showed that mitogen stimulation leads to an equivalent increase in transcription of the c-myc gene in T cells from old and young mice. Furthermore, in the presence of 5,6-dichlorobenzimidazole riboside, a selective inhibitor of RNA polymerase II, c-myc mRNA decayed with equal kinetics in cells from mice of different ages. These results show that lymphocytes from aged mice exhibit defects in gene expression very early in the activation process and suggest that these deficits may involve, at least for some genes, alterations in post-transcriptional processing.
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PMID:Defective T lymphocytes in old mice. Diminished production of mature c-myc RNA after mitogen exposure not attributable to alterations in transcription or RNA stability. 328 Jun 82

We have investigated whether the translocated and the untranslocated human c-myc oncogenes of Burkitt lymphoma cells are equally or differentially expressed in host mouse B cells. The human c-myc mRNA levels in somatic cell hybrids between mouse plasmacytoma cells and Burkitt lymphoma cells with either the t(8;14) or the t(2;8) chromosome translocation were determined by using the nuclease S1 protection procedure. Although both the human parental lines and the hybrid cells carrying the translocated c-muc oncogene expressed high levels of human specific c-myc transcripts, the hybrid cells carrying the untranslocated c-myc gene on normal chromosome 8 did not contain human specific c-myc mRNA. These results suggest that the translocated human c-myc oncogene has escaped the normal transcriptional control to which the untranslocated c-myc gene remains subjected. This interpretation is also supported by the finding that the expression of the c-myc genes of lymphoblastoid cells and of HL-60 promyelocytic leukemia cells are repressed when they are transferred into a mouse plasmacytoma background. The ability of the translocated c-myc oncogene to escape the normal transcriptional control occurring in B cells may be important for the expression of B cell neoplasia in mouse and man. We have also transferred the Burkitt 14q+ chromosome carrying a translocated c-myc oncogene into mouse LM-TK- fibroblasts and studied the levels of human c-myc transcripts in the hybrids. Because the levels of human c-myc transcripts in the fibroblast hybrids are dramatically decreased in comparison to the plasmacytoma hybrids, we conclude that the levels of transcripts of the translocated c-myc oncogene depend on the differentiated state of the cells harboring the translocated chromosome.
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PMID:Differential expression of the normal and of the translocated human c-myc oncogenes in B cells. 630 54

We have established the structure and nucleotide sequence of the 5' end of the human c-myc oncogene, using a cloned genomic fragment isolated from a fetal liver library (clone lambda MC41) and cloned cDNA from the human leukemic cell line K562. The human c-myc oncogene consists of three exons and two introns. Primer extension of the human c-myc mRNA of three different cell lines and S1 nuclease protection experiments served to establish the position of two transcription initiation sites. The splicing site of the first exon-intron boundary was determined by comparative analysis of the sequences of the genomic and cDNA clones. The first exon contains termination codons in all three reading frames and no translation initiation signals, confirming our previous observation that the c-myc mRNA has a long 5' noncoding sequence. This first exon also was found to be utilized in the formation of c-myc mRNAs in a variety of human cell lines.
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PMID:The structure and nucleotide sequence of the 5' end of the human c-myc oncogene. 657 11

In contrast to small-cell lung cancer, few data are available on the role of oncogene overexpression in non-small-cell lung cancers (NSCLC). To determine the prevalence and extent of the transcriptional activation of cancer genes in NSCLC we investigated the level of mRNA of the three important cellular oncogenes--erbB2, Ki-ras, and c-myc--in 39 surgically or endoscopically obtained tumor samples and 24 samples of normal bronchopulmonary tissue taken from the same patients. Tissue RNA was prepared and the specific mRNA analyzed by the highly sensitive nuclease S1 protection assay. Oncogene mRNA in the tumors was quantified by comparison with the homogeneously weak signals in normal lung tissue preparations with densitometry. The presence of two- to four-fold excess RNA was defined as moderate and a greater than fourfold RNA amount as strong gene overexpression. In contrast to normal tissue the oncogene mRNA amount varied considerably among tumors, showing increases up to 64-fold in erbB2, 13-fold in Ki-ras, and 57-fold in c-myc. Moderate and strong (in brackets) mRNA overexpression occurred with 33% (33%) in erbB2, 36% (18%) in Ki-ras, and 18% (23%) in c-myc. Simultaneous overexpression of two genes was observed with 41% and increased mRNA of all genes tested with 20% of the NSCLC samples. Augmented oncogene mRNA was observed most frequently in large-cell carcinoma. The c-myc overexpression was significantly more prevalent in large-cell cancer than in adenocarcinoma. Tumor differentiation was negatively correlated with c-myc mRNA amounts.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Oncogene overexpression in non-small-cell lung cancer tissue: prevalence and clinicopathological significance. 818 64

Much of our knowledge about the regulation of the c-myc proto-oncogene expression has come from studies of c-myc gene expression in several well defined ex vivo systems, including differentiation systems and tumor cells. However, very few investigations have been performed to determine the factors and cis-acting sequences that regulate c-myc expression in vivo. In order to obtain information on the sequences required to regulate c-myc gene transcription from the two major P1 and P2 initiation sites in the mouse, we have generated several constructs containing human or murine c-myc genomic sequences with various 5' flanking sequences and derived corresponding transgenic mice. A sensitive S1 nuclease protection assay was performed to analyse and to compare transgene expression with that of the endogenous c-myc mRNA, either in adult organs, or during development. None of the transgenic mice expressed the construct appropriately, although several strains exhibited unexpected expression most probably due to position effects. Our results indicate that the cis-acting elements described to regulate c-myc expression ex vivo are not sufficient to drive the correct expression of c-myc gene in vivo and strongly suggest that additional regulatory elements located upstream from -3500 (with respect to mouse P1 promoter) and downstream 1500 bp from polyadenylation sites are required.
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PMID:The cis-acting elements known to regulate c-myc expression ex vivo are not sufficient for correct transcription in vivo. 829 Feb 63

We have previously shown that in vivo the steady-state level of c-myc mRNA in different quiescent organs and its induction in the early stages of hepatic regeneration and after inhibition of protein synthesis are mainly controlled by post-transcriptional mechanisms. In order to localize the target sequences for these mechanisms, transgenic lines expressing various versions of the human c-myc proto-oncogene have been constructed. To avoid all possible transcriptional controls due to the c-myc 5' regulatory region, the c-myc genomic sequences were fused to MHC H-2Kb class I regulatory sequences, which have previously been shown to be able to drive reporter gene expression in most adult tissues. The transgenes contained either all human c-myc genomic sequences or were deleted for one of the sequences which have been shown in in vitro experiments to play a role in c-myc mRNA stabilization, in particular exon 1, intron 1 and the 3' non-coding region. Several independent transgenic lines were derived for each construct. Using S1 nuclease protection analysis, we have monitored H-2K, mouse c-myc and transgene mRNA expression in several quiescent adult organs, at the start of liver regeneration and after inhibition of protein synthesis in each transgenic line. Our results indicate that the 5' non-coding sequences, including exon 1 and intron 1, and the 3' untranslated region are all dispensable in the different aspects of c-myc post-transcriptional regulation.
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PMID:The 5' and 3' non-coding sequences of the c-myc gene, required in vitro for its post-transcriptional regulation, are dispensable in vivo. 851 Sep 35

Recently, it has been suggested that c-myc expression might correlate with estrogen receptor (ER) status and metastatic spread in ovarian cancer. In this study, expression of c-myc mRNA in 90 epithelial ovarian carcinomas was determined using the S1 nuclease protection assay. Expression of c-myc mRNA was detectable in 27 of 90 tumors. There was no significant association between c-myc mRNA expression and metastatic spread, survival time, FIGO stage, or histologic grade and type. C-myc mRNA was expressed in 45% of ER-positive tumors but only 24% of ER-negative tumors (p = 0.094; Fisher's exact test). Similarly, 44% of progesterone receptor (PR)-positive and 23% of PR-negative tumors expressed c-myc mRNA (p = 0.098). However, the association between c-myc mRNA expression and ER and PR status was not statistically significant. The ratio of mean expression of c-myc mRNA in patients with FIGO stages III/IV compared with patients with FIGO stages I/II was 2.1:1, an insignificant difference (p = 0.57, Wilcoxon rank sum test). In conclusion, c-myc was not significantly associated with the clinical parameters investigated in this study.
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PMID:C-myc mRNA expression in epithelial ovarian carcinomas in relation to estrogen receptor status, metastatic spread, survival time, FIGO stage, and histologic grade and type. 947 95


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