An interferon-induced phosphodiesterase degrading (2'-5') oligoisoadenylate and the C-C-A terminus of tRNA.

Schmidt, Azriel; Chernajovsky, Yuti; Shulman, Lester M.; Federman, P.; Berissi, Hanna; Revel, Michel

doi:10.1073/pnas.76.10.4788

Cited by 181 publications

(70 citation statements)

References 34 publications

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“…The accumulation of the inhibitor continued for at least 20 h although the rate of accumulation was most rapid in the first 6 h (data not shown). Since the extracts are likely to contain, in addition to the (2' -5')A,, synthetase, non-specific phosphatases and a phosphodiesterase which destroy (2'-5')A, [39], the data shown in Table 2 give an index of the (2'-5')A, synthetase induction, rather than exact levels of (2' -5')A,! synthetase activity.…”

Section: Induction Of' (2'-s') a Synthetasementioning

confidence: 99%

A Mouse Cell Line, which Is Unprotected by Interferon against Lytic Virus Infection, Lacks Ribonuclease F Activity

Epstein

Czarniecki

Jacobsen

et al. 1981

European Journal of Biochemistry

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A mouse cell line, N I H 3T3, does not respond to some of the activities of interferon. Even after treatment with high concentrations of interferon the replication of lytic viruses, such as encephalomyocarditis virus (EMCV) and vesicular stomatitis virus (VSV) is not inhibited in these cells. In contrast, interferon treatment of these same cells results in the inhibition of Moloney murine leukemia virus (MMuLV) production. We have analyzed enzymatic pathways which are induced by interferon in these cells. After interferon treatment, the level of the (2'-5')oligoadenylate [(2'-5')A,] synthetase activity and the phosphorylation of the 67000-dalton protein (PI) are enhanced in NIH 3T3 cells to approximately the same level as interferon-sensitive mouse L-cells. Moreover, NIH 3T3 and L-cells contain approximately the same levels of enzymcs which inactivate (2'-5')A,. Both exogenously added (2'-5')Aj or double-stranded RNA (ds RNA) failed to inhibit protein synthesis in NIH 3T3 extracts even though they were potent inhibitors of L-cell extract-directed protein synthesis. Direct measurements of the (2'-S')A,-dependent ribonuclease F (RNase F) failed to detect such activity in NIH 3T3 cells. Our results, therefore, suggest that the presence of RNase F activity is necessary for the interferon-induced antiviral activity against EMCV and against VSV. The induction of protein kinase activity by interferon treatment of NIH 3T3 cells appears to have no direct effect on EMCV and VSV replication.

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Section: Induction Of' (2'-s') a Synthetasementioning

confidence: 99%

A Mouse Cell Line, which Is Unprotected by Interferon against Lytic Virus Infection, Lacks Ribonuclease F Activity

Epstein

Czarniecki

Jacobsen

et al. 1981

European Journal of Biochemistry

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“…Interferons exhibit a number of biological activities including establishment of an antiviral state, inhibition of cell multiplication and enhancement of natural killer cell activity (Masucci et al, 1980). At the biochemical level, IFN has been shown to induce the synthesis of HLA antigens and fie microglobulin (Heron et al, 1978;FeUous et al, 1979) and to enhance a number of pre-existing enzyme activities including (2'-5')oligoadenylate synthetase (Kerr & Brown, 1978), protein kinase (Zilberstein et al, 1978), and 2'-phosphodiesterase (Schmidt et al, 1979).…”

Section: Introductionmentioning

confidence: 99%

Biological Activities and Receptor Binding of Two Human Recombinant Interferons and their Hybrids

Meister

Uzé

Mogensen

et al. 1986

Journal of General Virology

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SUMMARYTwo human recombinant lymphoblastoid interferon-0t subtypes, LylFN-B (~ts) and LyIFN-D (~q), and 10 hybrids generated therefrom were produced in Escherichia coli and purified. The antiviral and antiproliferative activities and the induction of (2'-5")oligoadenylate synthetase were compared to their receptor binding affinities. The IFN subtypes and their hybrids had similar specific antiviral activities on bovine cells. On human cells both the specific antiviral and antiproliferative activities of LylFN-B were about 30-fold higher than those of LyIFN-D. This difference in activity could be attributed partly to the N-terminal amino acids 1 to 60 and partly to amino acids 61 to 92. A third domain affecting the biological activities was found within the carboxyproximal segment from amino acids 93 to 150. The differences in these activities were found to correlate with their ability to bind the receptor, suggesting that the differences in activity might be due to altered binding of the IFNs to the cellular receptors. In contrast, the induction of (2'-5')oligoadenylate synthetase did not follow the same activity profile. On mouse cells, the efficiency of the hybrids was affected by at least four sites on the IFN protein. A hybrid with the N-terminal segment 1 to 60 from IFN-B and amino acids 61 to 166 from IFN-D had a specific antiviral activity on mouse cells as high as on human cells corresponding to a 500-and 5000-fold increase in specific activity compared to IFN-D and IFN-B, respectively. We suggest that on mouse cells the IFN activity may be more dependent on conformational differences than on human cells, which in turn might reflect a less precise fit to the mouse receptor than to the human receptor.

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“…Although characterization of 2Ј-PDE such as substrate specificity using a purified enzyme has been investigated (27,28), molecular characterization of 2Ј-PDE has remained to be elucidated. To understand the molecular mechanism and biological role of the 2-5A system more precisely, identification of 2Ј-PDE is indispensable.…”

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confidence: 99%

Identification of 2′-Phosphodiesterase, Which Plays a Role in the 2-5A System Regulated by Interferon

Kubota

Nakahara

Ohtsuka

et al. 2004

Journal of Biological Chemistry

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The 2-5A system is one of the major pathways for antiviral and antitumor functions that can be induced by interferons (IFNs). The 2-5A system is modulated by 5-triphosphorylated, 2,5-phosphodiester-linked oligoadenylates (2-5A), which are synthesized by 2,5-oligoadenylate synthetases (2,5-OASs), inactivated by 5-phosphatase and completely degraded by 2-phosphodiesterase (2-PDE). Generated 2-5A activates 2-5A-dependent endoribonuclease, RNase L, which induces RNA degradation in cells and finally apoptosis. Although 2,5-OASs and RNase L have been molecularly cloned and studied well, the identification of 2-PDE has remained elusive. Here, we describe the first identification of 2-PDE, the third key enzyme of the 2-5A system. We found a putative 2-PDE band on SDS-PAGE by successive six-step chromatographies from ammonium sulfate precipitates of bovine liver and identified a partial amino acid sequence of the human 2-PDE by mass spectrometry. Based on the full-length sequence of the human 2-PDE obtained by in silico expressed sequence tag assembly, the gene was cloned by reverse transcription-PCR. The recombinant human 2-PDE expressed in mammalian cells certainly cleaved the 2,5-phosphodiester bond of 2-5A trimer and 2-5A analogs. Because no sequences with high homology to this human 2-PDE were found, the human 2-PDE was considered to be a unique enzyme without isoform. Suppression of 2-PDE by a small interfering RNA and a 2-PDE inhibitor resulted in significant reduction of viral replication, whereas overexpression of 2-PDE protected cells from IFN-induced antiproliferative activity. These observations identify 2-PDE as a key regulator of the 2-5A system and as a potential novel target for antiviral and antitumor treatments.

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An interferon-induced phosphodiesterase degrading (2'-5') oligoisoadenylate and the C-C-A terminus of tRNA.

Abstract: A phosphodiesterase characterized by a generally higher activity on 2'-5' than on 3'-5' phosphodiester bonds was isolated from mouse L cells treated with interferon.

Cited by 181 publications

References 34 publications

A Mouse Cell Line, which Is Unprotected by Interferon against Lytic Virus Infection, Lacks Ribonuclease F Activity

A Mouse Cell Line, which Is Unprotected by Interferon against Lytic Virus Infection, Lacks Ribonuclease F Activity

Biological Activities and Receptor Binding of Two Human Recombinant Interferons and their Hybrids

Identification of 2′-Phosphodiesterase, Which Plays a Role in the 2-5A System Regulated by Interferon

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