Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.30.2 (endonuclease)
 18,621 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Of 17 Moloney murine leukemia virus (MoMuLV)-induced rat thymomas, 2 contained rearrangements in c-myc. In one of these tumors the observed rearrangement was not due to the insertion of an intact MoMuLV provirus. The rearranged c-myc DNA fragment from this thymoma was cloned and examined by restriction endonuclease mapping, hybridization to MoMuLV proviral DNA probes, and DNA sequence analysis. These analyses revealed that the c-myc rearrangement in this tumor was due to the presence of a partially duplicated MoMuLV long terminal repeat (LTR) 5' to c-myc exon 1. The orientation of this LTR structure was opposite to the transcriptional orientation of c-myc. The sequences at the 3' flanking side of the LTR structure were derived from a cellular DNA region which maps to the same chromosome as c-myc (chromosome 7), although to a site distant from this proto-oncogene. These findings present evidence for a homologous recombination event occurring between sequences of two proviruses integrated on the same chromosome, one of which was inserted near the c-myc proto-oncogene. The recombination product contains three copies of the MoMuLV LTR 72-base-pair direct repeat and is associated with a high level of c-myc expression. The reciprocal product of this recombination was not detected. We propose that recombination between homologous sequences may play a significant role in the generation of chromosomal rearrangements and therefore in tumor induction and progression.
 ...
PMID:Recombination between two integrated proviruses, one of which was inserted near c-myc in a retrovirus-induced rat thymoma: implications for tumor progression. 327 24

We determined a complete nucleotide sequence of an activated form of the c-H-ras-1 proto-oncogene cloned from the human cell line (QG56), using the DNA transfection technique and NIH3T3 cells as recipients. This cell line was established from a squamous-cell lung carcinoma of a Japanese patient, and the activated gene had 2 nucleotide substitutions. One substitution of a thymidine for an adenosine was found at position 1069 of the 2898 nucleotide sequence in a restriction endonuclease (SacI) fragment, which corresponds to the second base of the 61st codon of the gene encoding P21 protein. This nucleotide replacement was assumed to be responsible for the transforming activity. Another substitution of a guanosine for an adenosine which was detected at position 746 in the first intron was thought to be a genetic polymorphism unassociated with the transforming activity. Comparison of the various lengths of restricted fragments suggested that the activity was markedly influenced by certain sequences flanking the c-H-ras-1 gene.
 ...
PMID:Isolation and characterization of an activated C-H-ras-1 gene from a squamous-cell lung carcinoma cell line. 400 2

A mammalian apurinic/apyrimidinic endonuclease (AP endonuclease) is known to have two distinct functional domains. One domain is responsible for regulating the activity of Fos/Jun proto-oncogene products to bind to DNA at specific recognition sites. The other domain, which is highly conserved from bacteria to mammals, is responsible for repairing DNA damage caused by ionizing radiation, oxidative damage, and alkylating agents. This study reports on the isolation and characterization of the genomic structure of the mouse AP endonuclease gene (Apex). The genomic sequence of the Apex gene was 2.14 kb in length and contained four exons. Exon 1 contained a 0.24-kb untranslated 5' region upstream of the initiation codon. Consensus sequences for two CAAT boxes and a GC box were found upstream of the end of exon 1. A polymorphism was noted in the untranslated region of exon 1 in a comparison of a number of mouse strains. These data indicate that the 5' end of the mouse gene (Apex) differs from the previously isolated human gene (Ape), which has five exons and an untranslated region between exons 1 and 2. Data are also presented that suggest the presence of two pseudogenes in the mouse.
 ...
PMID:Genomic structure of the mouse apurinic/apyrimidinic endonuclease gene. 753 13

Past studies have shown that serum-free cultures of PC12 cells are a useful model system for studying the mechanisms of neuronal death after neurotrophic factor deprivation. These cultures, as well as NGF-deprived cultures of sympathetic neurons, manifest and endonuclease activity that leads to "apoptotic" internucleosomal DNA cleavage. Overexpression of the proto-oncogene bcl-2 blocks apoptotic death in various cell types. To study the actions of this protein in neuronal cells, we derived PC12 cell lines stably transfected with a cDNA encoding human bcl-2. It is reported here that lines expressing high levels of the exogenous bcl-2 protein are protected from both death and apoptotic DNA fragmentation caused by removal of trophic support. However, expression of high levels of exogenous bcl-2 neither mimics nor interferes with promotion of neurite outgrowth by NGF.
 ...
PMID:Bcl-2 affects survival but not neuronal differentiation of PC12 cells. 769 14

C-erbB-2(HER-2/neu) proto-oncogene is mainly expressed in epithelial tissue and activated due to its amplification. Amplification of the C-erbB-2 proto-oncogene has been associated with poor prognosis in human ovarian cancer. Our study was to examine whether amplification is more frequently observed in ovarian cancer, or it is associated with poor prognosis of human ovarian cancer in China. The DNA of ovarian cancers was extracted and consequently digested with restriction endonuclease EcoRI, electrophoresed in 0.8% agarose gels and blotted onto nitrocellulose filter with Southern transferring method. It was then hybridized with a 32P-labelled C-erbB-2 probe and subsequently underwent autoradiography. The result has shown that the C-erbB-2(HER-2/neu) gene was amplified in 8 of 26 human ovarian cancers (30.8%). The clinical data showed that all of the 8 cases with the amplified C-erbB-2 were in their advanced stage (III-IV). Five of the patients died from 2 to 4 months after operation. These data suggest that amplification of the C-erbB-2 gene may play a role in the pathogenesis of ovarian carcinoma; it is frequently observed in advanced ovarian cancer and is associated with poor prognosis for these patients.
 ...
PMID:Amplification of the C-erbB-2(HER-2/neu) proto-oncogene in ovarian carcinomas. 780 42

C-erbB-2 (HER-2/neu) proto-oncogene is mainly expressed in epithelial tissue and activated due to its amplification. Amplification of the C-erbB-2 proto-oncogene is associated with poor prognosis in human ovarian cancer. We examined whether amplification of C-erbB-2 is common in ovarian carcinoma or is associated with poor prognosis. The DNA of ovarian carcinoma was extracted and consequently digested with restriction endonuclease EcoRI, electrophoresed in 0.8% agarose gels and blotted onto nitrocellulose filter with Southern transfering method. It was hybridized with a 32p-labelled C-erbB-2 probe and subsequently underwent autoradiography. It was shown that the C-erbB-2 (HER-2/neu) gene was amplified in 8 of 26 human ovarian carcinomas (30.8%). Clinically the 8 patients with the amplified C-erbB-2 were in their advanced stage (III-IV). Five of the patients died from 2 to 4 months after operation. These findings suggest that amplification of the C-erbB-2 gene may play a role in the pathogenesis of ovarian carcinoma, it is frequently observed in advanced ovarian carcinoma and associated with poor prognosis for these patients.
 ...
PMID:[The relation between prognosis and amplification of the c-erB-2 (HER-2/neu) proto-oncogene in ovarian carcinomas]. 786 5

The phenomenon of superinduction refers to the process by which high concentrations of protein synthesis inhibitors augment and stabilize mRNA transcript levels, e.g. 36-180 microM of Puromycin (PM) has been found to elicit c-myc mRNA superinduction. The expression of the proto-oncogene c-myc has been strongly variously implicated in the regulation of the apoptotic cascade. Since we recently found that a low dose of the protein synthesis inhibitor PM activated the apoptotic cascade in HL-60 leukaemic cells, the current study was undertaken to examine c-myc mRNA transcript levels in such cells, and to assess the relationship, if any, between PM-elicited c-myc mRNA superinduction and subsequent activation of the apoptotic cascade. PM was employed in vitro at doses of 0.9 microM and 2 microM. Dose-dependent c-myc mRNA superinduction was present at 1 hour of PM-exposure, and was associated with subsequent activation of the apoptotic cascade at 24 hours of exposure. Apoptosis was confirmed morphologically as evidenced by chromatin condensation, nuclear fragmentation and the formation of apoptotic bodies, and by DNA agarose gel electrophoresis which showed the pattern of double-stranded DNA fragments that result from the activation of an endogenous endonuclease. [C14]Leucine incorporation studies at 1 hour demonstrated minimal protein synthesis inhibition at doses used, suggesting that c-myc mRNA superinduction in this context may have been the result of mechanisms which were independent of the inhibition of synthesis of new proteins, such as interruptions in signal transduction.
 ...
PMID:Puromycin-elicited c-myc mRNA superinduction precedes apoptosis in HL-60 leukaemic cells. 829 42

Anucleate cells can be induced to undergo programmed cell death (PCD), indicating the existence of a cytoplasmic PCD pathway that functions independently from the nucleus. Cytoplasmic structures including mitochondria have been shown to participate in the control of apoptotic nuclear disintegration. Before cells exhibit common signs of nuclear apoptosis (chromatin condensation and endonuclease-mediated DNA fragmentation), they undergo a reduction of the mitochondrial transmembrane potential (delta psi m) that may be due to the opening of mitochondrial permeability transition (PT) pores. Here, we present direct evidence indicating that mitochondrial PT constitutes a critical early event of the apoptotic process. In a cell-free system combining purified mitochondria and nuclei, mitochondria undergoing PT suffice to induce chromatin condensation and DNA fragmentation. Induction of PT by pharmacological agents augments the apoptosis-inducing potential of mitochondria. In contrast, prevention of PT by pharmacological agents impedes nuclear apoptosis, both in vitro and in vivo. Mitochondria from hepatocytes or lymphoid cells undergoing apoptosis, but not those from normal cells, induce disintegration of isolated Hela nuclei. A specific ligand of the mitochondrial adenine nucleotide translocator (ANT), bongkreik acid, inhibits PT and reduces apoptosis induction by mitochondria in a cell-free system. Moreover, it inhibits the induction of apoptosis in intact cells. Several pieces of evidence suggest that the proto-oncogene product Bcl-2 inhibits apoptosis by preventing mitochondrial PT. First, to inhibit nuclear apoptosis, Bcl-2 must be localized in mitochondrial but not nuclear membranes. Second, transfection-enforced hyperexpression of Bcl-2 directly abolishes the induction of mitochondrial PT in response to a protonophore, a pro-oxidant, as well as to the ANT ligand atractyloside, correlating with its apoptosis-inhibitory effect. In conclusion, mitochondrial PT appears to be a critical step of the apoptotic cascade.
 ...
PMID:Mitochondrial control of nuclear apoptosis. 866 86

The development of atherosclerotic plaques is characterised by the accumulation of lipids and the proliferation of smooth muscle cells. At the subcellular level, the abnormal expression of cytokines and growth factors, as well as the presence of transforming oncogenes, has been recognised and associated with the disease. The aim of the present study was to investigate whether instability at a minisatellite region located downstream of the H-ras proto-oncogene possessing enhancer activity, is a detectable phenomenon in atherosclerotic plaques. Thirty specimens were analysed by polymerase chain reaction (PCR) in order to reveal alterations of the repetition number and by restriction fragment length polymorphism (RFLP) with BstNI restriction endonuclease for the detection of point mutations within the 28 bp core repetitive element. No point mutations were found among the 30 cases tested; however, alterations of the repetition number of the core were detected in 5 (17%) cases. Our results suggest that instability at the H-ras minisatellite may be associated with development of the disease.
 ...
PMID:Instability at the H-ras minisatellite in human atherosclerotic plaques. 883 26

We describe the case of a 69-year-old man with systemic mastocytosis and severe osteopetrosis who carries a somatic activating mutation in the c-kit proto-oncogene. The patient initially presented with urticaria pigmentosa, progressing to systemic mast cell disease with severe anemia due to bone marrow involvement, chronic diarrhea, and hepatosplenomegaly. Direct sequencing using amplimers from reverse transcriptase-polymerase chain reactions (RT-PCR) from skin mast cell-derived RNA revealed a point mutation in the c-kit proto-oncogene at position 2468, introducing a new recognition site for the restriction endonuclease HinfI. Treatment with interferon-alpha 2a, prednisone, and erythropoietin was initiated. Subsequently, clinical symptoms improved significantly and hemoglobin levels are now stable at 13 g/dl.
 ...
PMID:c-kit mutation and osteopetrosis-like osteopathy in a patient with systemic mast cell disease. 979 83


<< Previous 1 2 3 Next >>