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:3.1.30.2 (endonuclease)
18,621 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Erythropoietin (EPO) retards DNA breakdown characteristic of programmed cell death (apoptosis) and promotes survival in erythroid progenitor cells. The mechanism by which EPO inhibits programmed death is unknown. In the well-characterized model of glucocorticoid-treated thymocytes, activation of a Ca2+/Mg(2+)-sensitive endonuclease and new protein and RNA syntheses have been found necessary for apoptosis. We examined the effects of EPO on the free intracellular calcium ion concentration ([Ca2+]i), and the roles of Ca2+ and RNA and protein syntheses on DNA cleavage in erythroid progenitor cells. The murine model of erythroid differentiation using Friend leukemia virus-infected proerythroblasts (FVA cells) was used. EPO did not affect the [Ca2+]i in FVA cells. Decreasing [Ca2+]i by extracellular Ca2+ chelation with EGTA facilitated DNA breakdown. Increasing [Ca2+]i with the calcium ionophore 4-bromo-A23187 increased DNA cleavage; however, DNA fragments generated by high [Ca2+]i were much larger than those seen in the absence of EPO or presence of EGTA. Increased [Ca2+]i also inhibited DNA breakdown to small oligonucleosomal fragments characteristic of cells cultured without EPO. However, no concentration of ionophore protected the high molecular weight DNA as did EPO. Cycloheximide inhibited DNA breakdown in a dose dependent manner in cultures lacking EPO, but two other protein synthesis inhibitors, pactamycin and puromycin, did not prevent DNA breakdown. Inhibition of RNA synthesis with actinomycin D did not prevent DNA breakdown. Cells with morphological characteristics similar to those reported in other cells undergoing programmed death accumulated in EPO-derived cultures. These studies demonstrate that although DNA cleavage and morphological changes are common to apoptotic cells, the roles for Ca2+ and protein and RNA syntheses are not universal and suggest that apoptosis can be regulated by different biochemical mechanisms in different cell types.
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PMID:Regulation of programmed death in erythroid progenitor cells by erythropoietin: effects of calcium and of protein and RNA syntheses. 128 50

A number of Friend leukemia cell variants with a interferon-gamma (IFN-gamma)-resistant phenotype have been isolated. They appear resistant to the antiproliferative action of IFN-gamma and to the induction of the antiviral state assessed by Friend leukemia virus release and vesicular stomatitis virus yield. Selection was performed via a prolonged exposure to increasing amounts of highly purified recombinant IFN-gamma of wild-type Friend cells or of variant clones thereof already resistant to IFN-alpha/beta (Affabris et al., 1982, Virology 120, 441-452). Only the clones derived from IFN-alpha/beta-resistant variants showed a phenotype fully resistant to IFN-gamma treatment while keeping their previously acquired resistance to IFN-alpha/beta. These cells are not deficient in high-affinity receptors for IFN-gamma so that their resistant phenotype appears to be mediated by events distal to binding of IFN-gamma to its receptors. Furthermore, analysis of IFN-induced dsRNA-dependent 2-5A synthetase and 67K protein kinase enzymatic activities, biochemical markers for cellular responses to IFN, showed that both these activities were not induced in IFN-alpha/beta and IFN-gamma-resistant clones when treated with either type of IFN. Accordingly, no increased expression of 2-5A synthetase mRNA(s) could be detected by probing poly(A)+-enriched RNA from cells exposed to IFN-alpha/beta or IFN-gamma treatment with murine or human specific cDNAs. On the other hand, no major changes in restriction patterns of 2-5A synthetase gene(s) were observed in these variant cells by restriction endonuclease digestion and Southern blotting. In addition, analysis of 2-5A synthetase mRNA induction, performed on wild-type cells, showed that the kinetic of induction due to IFN-gamma treatment is slower than that obtained with IFN-alpha/beta.
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PMID:Interferons-alpha/beta- and -gamma-resistant Friend cell variants exhibiting receptor sites for interferons but no induction of 2-5A synthetase and 67K protein kinase. 296 42

An endonuclease activity shown to be associated with Friend leukemia virus has been characterized using double-stranded phi X174 DNA as substrate. In the presence of Mg2+, the endonuclease activity was able to convert supercoiled circular DNA duplexes to the relaxed form by introducing single-stranded nicks into the DNA. Most of the nicked DNA duplexes contained only one nick per strand, since unit length DNA was the predominant species obtained when the nicked DNA was analyzed by alkaline sucrose gradient centrifugation. The regions into which the nick could be introduced were evenly distributed around the circular DNA molecule. When Mn2+ was substituted for Mg2+ in the reaction mixture, the number of nicks introduced into circular DNA duplexes by the virus associated endonuclease was greatly increased. In contrast to circular duplexes, linear duplexes and single-stranded DNA functioned poorly as substrates for the virus-associated enzyme. The Friend leukemia virus-associated endonuclease activity is with respect to these characteristics very similar to the endonuclease activity associated with the p32 protein of the avian myeloblastosis virus [1]. The molecular weight of the Friend leukemia virus endonuclease was estimated by gel filtration on a Sephacryl S-200 column to be about 45 000.
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PMID:Characterization of an endonuclease activity associated with Friend-murine leukemia virus. 625 Jun 13

An endonuclease associated with the core of Friend leukemia virus (FLV) has been purified more than 10(3)-fold by ion exchange chromatography and gel filtration. Its molecular weight was determined by gel filtration to be about 40,000. Divalent cations were required for the endonuclease to function and KCl concentrations above 50 mM inhibited the enzyme activity. In the presence of Mg++ the purified enzyme nicked preferentially supercoiled circular DNA duplexes and in most of these molecules only one single-stranded nick was introduced per strand. The regions into which the nick could be introduced appeared to be randomly distributed on the circular molecule. When Mn++ was substituted for Mg++ the number of nicks introduced into DNA by the purified enzyme was greatly increased, and both relaxed circular and linear DNA duplexes were nicked as well as supercoiled circular DNA duplexes. Prior to its purification, however, in the presence of Mn++ the endonuclease activity in the virus extract was able to differentiate between circular and linear DNA duplexes, since both supercoiled and relaxed circular duplexes were nicked much more readily than linear duplexes. Single-stranded DNA functioned poorly as a substrate for the purified enzyme.
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PMID:Purification and properties of DNA endonucleases associated with Friend leukemia virus. 625 41

The integrated proviral DNA of the polycythemia-inducing isolate of Friend spleen focus-forming virus (SFFVp) has been identified in rat cell clones nonproductively infected with this replication-defective erythroleukemia virus and cloned in phage lambda vectors. These lambda SFFVp recombinants, lambda SFFVp502 and lambda SFFVp542, contain endonuclease EcoRI inserts of size 7.4 and 8.2 kilobases, respectively, and include full copies of the SFFVp genome, along with host flanking sequences. Infectivity of the cloned SFFVp genomes was tested by a two-step DNA transfer procedure involving transfection of the cloned DNA into 3T3 mouse fibroblasts or cotransfer of the cloned DNA into thymidine kinase-deficient 3T3 cells together with the cloned thymidine kinase gene of herpes simplex virus, followed by rescue of the transferred DNA by superinfection with a helper virus. Inoculation of the rescued virus into adult mice resulted in the appearance of spleen foci, rapid splenomegaly, and polycythemia. Early after infection, spleen cell populations contained large numbers of cells capable of forming small erythroid colonies in vitro (CFU-E) in the absence of erythropoietin. Late after infection, these mice contained cells capable of forming macroscopic colonies (CFU-FV) in vitro. These data indicate that molecular clones of SFFVp, in conjunction with a helper virus, induce the appearance of hemopoietic colony-forming cells characteristic of both the early and late stages of Friend leukemia.
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PMID:Clonal analysis of early and late stages of erythroleukemia induced by molecular clones of integrated spleen focus-forming virus. 627 94

Globin structural genes from a murine erythroleukemia cell line were analyzed by Southern blot hybridization of genomic DNA and after isolation of cloned globin genes from a genomic library. The globin genes isolated from the erythroid cell line did not differ, when analyzed by extensive restriction endonuclease digestion, from globin genes isolated from nonerythroid cells. No gross structural differences were seen between murine erythroleukemia globin genes, either before or after hexamethylene bisacetamide (HMBA)-mediated erythroid differentiation, and globin genes from normal mouse liver DNA. Whereas the murine erythroleukemia genome hybridizes extensively to cloned Friend leukemia virus probes, there was no evidence of viral integration into sequences adjacent to the globin genes.
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PMID:Analysis of globin genes from murine erythroleukemia cells. 630 19

We have identified a cellular target for proteasomal endonuclease activity. Thus, 20 S proteasomes interact with the 3'-untranslated region of certain cytoplasmic mRNAs in vivo, and 20 S proteasomes isolated from Friend leukemia virus-infected mouse spleen cells were found to be associated with a mRNA fragment showing great homology to the 3'-untranslated region of tumor necrosis factor-beta mRNA that contains AUUUA sequences. We furthermore demonstrate that 20 S proteasomes destabilize oligoribonucleotides corresponding to the 3'-untranslated region of tumor necrosis factor-alpha, creating a specific cleavage pattern. The cleavage reaction is accelerated with increasing number of AUUUA motifs, and major cleavage sites are localized at the 5' side of the A residues. These results strongly suggest that 20 S proteasomes could be involved in the destabilization of cytokine mRNAs such as tumor necrosis factor mRNAs and other short-lived mRNAs containing AUUUA sequences.
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PMID:Possible involvement of proteasomes (prosomes) in AUUUA-mediated mRNA decay. 1002 17

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