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)

The promoter region of the IL2R alpha gene 5' flanking sequence contains enhancer elements crucial for binding nuclear factors which upregulate transcription following T lymphocyte activation. A 3' exonuclease resistant oligonucleotide (3'A-IL28p, terminated by a free amine group at its 3' end) was designed to bind to the IL2R alpha promoter region from -273 to -246, forming a collinear triplex spanning the kappa B enhancer (-266 to -256) as well as most of the serum response element (CArG box, -251 to -244). The binding site specificity of this oligonucleotide was demonstrated in electrophoretic mobility shift assays and by inhibition of restriction endonuclease (HinfI) cleavage within the segment of the target DNA predicted to form a triplex with the oligonucleotide. Intact normal lymphocytes, preincubated for 2h with 3'A-IL28p, accumulated less IL2Ralpha mRNA relative to other mRNAs (c-myc, beta-actin, IL2R beta, IL-6) for up to 12h after PHA stimulation, than did lymphocytes treated with a control oligomer of similar composition but different sequence. Nuclear run-on studies demonstrated that the rate of IL2R alpha mRNA synthesis relative to c-myc and beta-actin was also selectively diminished by treatment with 3'A-IL28p. These experiments suggest that transcription of individual genes can be selectively modulated in living cells by sequence specific collinear triplex formation in regulatory enhancer sequences.
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PMID:Oligonucleotide inhibition of IL2R alpha mRNA transcription by promoter region collinear triplex formation in lymphocytes. 206 58

Increased levels of soluble activity of all three enzymes involved in polyadenylic acid metabolism were measured in PHA-stimulated versus normal lymphocytes. Poly(A)-polymerase and poly(A)-exonuclease values increased significantly (from 25.7 +/- 4.2 (S.E.M.) to 53.5 +/- 10.6 (S.E.M.), and from 334.6 +/- 33.2 (S.E.M.) to 653.2 +/- 53.4 (S.E.M.) respectively), while a moderate increase was observed in poly(A)-endonuclease (from 299.2 +/- 33.8 (S.E.M.) to 403.0 +/- 77.1 (S.E.M.). The above differences persisted after two fractionations of the crude cell extracts by ion exchange chromatography and molecular sieving, and could not be attributed to the competitive action of all three enzymes in the untreated extracts. Fractionation of the extracts of resting and stimulated cells on Sephadex G-75 revealed two molecular forms of poly(A)-polymerase activity.
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PMID:Increase in the levels of activity of polyadenylic acid-metabolizing enzymes following phytohaemagglutinin stimulation of human lymphocytes. 304 Nov 99

Fludarabine phosphate selectively eliminates normal and malignant mononuclear cells in large animals and man through the inhibition of DNA synthesis. The drug depletes mononuclear cells from culture within 24 hours of initial exposure, CD4 and CD8 T cells being more sensitive than either CD20 B cells or CD34 bone marrow precursors. Mitogenic activation of lymphocytes enhances cellular elimination from culture. Fludarabine inhibits PHA-induced T-cell proliferation by >90 per cent and mixed lymphocyte reactions (allogeneic and xenogeneic) by >95 per cent. Fludarabine exerts its cytolytic effects through the induction of endonuclease-independent apoptosis. A 5-day course of fludarabine (50 mg/m2 intravenously once daily) induces both T- and B-cell lymphopenia in Cynomolgus monkeys and Papio baboons. Transient neutropenia was the only side-effect seen in experimental animals. Pretreatment of Cynomolgus monkeys with this regimen of fludarabine causes a prolongation of ABO-compatible skin allograft survival from 8 days (control) to 16 days (drug treated group). Secondary allotransplantation into presensitized recipients showed a similar prolongation of graft survival with fludarabine pretreatment (8 days vs 5 days control). Fludarabine promises to be a potent immunosuppressive agent with low clinical toxicity.
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PMID:Fludarabine phosphate: A DNA synthesis inhibitor with potent immunosuppressive activity and minimal clinical toxicity. 865 23

A collection of Pseudomonas corrugata and P. mediterranea strains, two closely related species, was evaluated for the presence and variability of pha loci. Using PCR methods that specifically amplify segments of medium-chain-length poly(hydroxyalkanoate) (mcl-PHA) synthase genes, we demonstrated the presence of phaC1 and phaC2 in all P. mediterranea strains tested and in six out of 56 strains of P. corrugata screened. The remaining 50 strains of P. corrugata yielded only the phaC2 subgene fragment on detection by a combined PCR-restriction endonuclease analysis method or a semi-nested PCR-amplification approach. A Southern hybridization study on a representative strain from this group, however, indicated the presence of the phaC1 gene. Nucleic acid sequences of the subgene phaC fragments of the representative strains from the three groups showed an overall similarity ranging from 95% to 100%. The major repeat-unit monomers of the mcl-PHAs isolated from these selected strains are beta-hydroxyoctanoate (33-47 mol%) and beta-hydroxydecanoate (26-36 mol%). These results differentiate for the first time the strains of P. corrugata into two pha-distinguishable groups. This study also documents for the first time the production of mcl-PHA in P. mediterranea.
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PMID:Poly(hydroxyalkanoate) synthase genotype and PHA production of Pseudomonas corrugata and P. mediterranea. 1572 40