Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.5.4.4 (adenosine deaminase)
 5,136 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

2',5'-oligoadenylate synthetase (2-5OAS) has been studied in peripheral blood mononuclear cells from nine patients with hairy cell leukaemia (HCL) receiving therapy with the adenosine deaminase inhibitor deoxycoformycin (dCF) or alpha interferon (alpha-IFN). 2-5OAS mRNA was assayed by dot-blot hybridization. Increase of 2-5OAS mRNA level was seen in six patients with HCL treated with dCF and in one patient treated with alpha-IFN who responded to therapy. A patient with a variant form of HCL treated with dCF and the second patient treated with alpha-IFN did not show an increase of 2-5OAS mRNA and neither responded to therapy. The 15 other patients with T or B-chronic lymphoblastic leukaemia (CLL), T-acute lymphoblastic leukaemia (ALL), adult T-cell leukaemia lymphoma (ATLL), non-Hodgkins lymphoma (NHL), Sezary and T or B-prolymphocytic leukaemia (PLL) treated with dCF did not show an increase in 2-5OAS, though four patients, all with T-cell tumours, responded clinically. 2-5OAS activity is known to be stimulated by alpha-IFN and recent work suggests that this rise in 2-5OAS may result in increased cleavage of mRNA for tumour necrosis factor (TNF) and other cytokines on which autocrine growth and proliferation of the tumour cells are dependent. By analogy, we suggest that one mechanism of action of dCF in hairy cell leukaemia may be to break down an autocrine growth loop for TNF or other cytokines. An alternative explanation for these observations is that cytokines released from hairy cells in the bone marrow killed by dCF induce a rise in 2-5OAS in circulating leucocytes.
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PMID:Increase in 2',5'-oligoadenylate synthetase caused by deoxycoformycin in hairy cell leukaemia. 155 Jul 76

There is evidence that 2'-deoxycoformycin (DCF) functions as a differentiating agent. We examined the effects of DCF on the differentiation of HL-60 cells, a standard model of leukemic cell differentiation. DCF did not induce morphologic or histochemical evidence of differentiation, nor did it interact with retinoic acid, 1,25-dihydroxyvitamin D3, or interferon-gamma in inducing differentiation. Furthermore, DCF and agents that differentiated HL-60 cells had opposing effects on adenosine deaminase and 2',5'-oligoadenylate synthetase activity.
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PMID:Effects of 2'-deoxycoformycin on HL-60 cell differentiation, adenosine deaminase, and oligoadenylate synthetase. 231 12

Tremendous progress has been made in understanding the molecular basis of the antiviral actions of interferons (IFNs), as well as strategies evolved by viruses to antagonize the actions of IFNs. Furthermore, advances made while elucidating the IFN system have contributed significantly to our understanding in multiple areas of virology and molecular cell biology, ranging from pathways of signal transduction to the biochemical mechanisms of transcriptional and translational control to the molecular basis of viral pathogenesis. IFNs are approved therapeutics and have moved from the basic research laboratory to the clinic. Among the IFN-induced proteins important in the antiviral actions of IFNs are the RNA-dependent protein kinase (PKR), the 2',5'-oligoadenylate synthetase (OAS) and RNase L, and the Mx protein GTPases. Double-stranded RNA plays a central role in modulating protein phosphorylation and RNA degradation catalyzed by the IFN-inducible PKR kinase and the 2'-5'-oligoadenylate-dependent RNase L, respectively, and also in RNA editing by the IFN-inducible RNA-specific adenosine deaminase (ADAR1). IFN also induces a form of inducible nitric oxide synthase (iNOS2) and the major histocompatibility complex class I and II proteins, all of which play important roles in immune response to infections. Several additional genes whose expression profiles are altered in response to IFN treatment and virus infection have been identified by microarray analyses. The availability of cDNA and genomic clones for many of the components of the IFN system, including IFN-alpha, IFN-beta, and IFN-gamma, their receptors, Jak and Stat and IRF signal transduction components, and proteins such as PKR, 2',5'-OAS, Mx, and ADAR, whose expression is regulated by IFNs, has permitted the generation of mutant proteins, cells that overexpress different forms of the proteins, and animals in which their expression has been disrupted by targeted gene disruption. The use of these IFN system reagents, both in cell culture and in whole animals, continues to provide important contributions to our understanding of the virus-host interaction and cellular antiviral response.
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PMID:Antiviral actions of interferons. 1158 85