The 2′5′ oligoadenylate synthetase has a multifunctional 2′5′ nucleotidyl-transferase activity

Ferbus, Didier; Justesen, Just; Besançon, Françoise; Thang, M.N.

doi:10.1016/s0006-291x(81)80251-3

Cited by 42 publications

(33 citation statements)

References 21 publications

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“…This is in contrast to Ferbus et al [15] who have found that NAD' and ATP are used with equal efficiencies by the enzyme from reticulocyte lysates. Good conversion to the putative products NADf2'p5'A and NAD+2'p5'A2'p5'A is obtained with 1 pM NAD' and 1 mM ATP, whereas with micromolar ATP alone very little ATP is converted to ppp(A2'p),A.…”

Section: Synthesis and Purfication Of Ppp(a2'pla Analoguescontrasting

confidence: 96%

“…Nejther NADP' (which has no free 2'-hydroxyl group on the adenine ribose) nor N M N is a primer for the ppp(A2'p)"A synthetase (see also [13,15,16]); this strongly suggests that the S'AMP is linked to the adenine ribose ring. Further evidence in favour of this was provided by the activity of the putative NADC2'p5'A2'p5'A in the radiobinding assay.…”

Section: Synthesis and Purfication Of Ppp(a2'pla Analoguesmentioning

confidence: 99%

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Synthesis, Characterisation and Biological Significance of (2′‐5′)Oiigoadenylate Derivatives of NAD⁺, ADP‐Ribose and Adenosine(5′)Tetraphosph0(5′)Adenosine

Cayley

Kerr

1982

European Journal of Biochemistry

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The (2′‐5′)oligoadenylate synthetase [ppp(A2′p)n,A synthetase] from interferon‐treated HeLa cells has been used to synthesize NAD+2′p5′A and NAD′2′p5′A2′p5′A. High‐performance liquid chromatography conditions have been developed for the separation of these products and the structures of the purified nucleotides confirmed by proton nuclear magnetic resonance spectroscopy. Using A5′p45′A and ADP‐ribose as primers the corresponding series of (2′‐5′)oligoadenylate products have been similarly synthesised and purified. All of the analogues whose structure includes pp(A2′p)2A were found to displace ppp(A2′p)3A[32P]pCp in the radiobinding assay for ppp(A2′p)nA (n = 2 to ≥ 4) [M. Knight et al. (1980) Nature (Lond.) 288, 189–192] at the same concentration (nanomolar) as does ppp(A2′p),A. They also have the same stability as ppp(A2′p)nA under protein‐synthesis conditions in Ehrlich ascites tumour cell extracts. A5′p,5′(A2′p)4A and A5′p45′(A2′p)3A inhibit protein synthesis in Ehrlich ascites tumour extracts as effectively as ppp(A2′p)2A. A5′p45′(A2′p)3A activates the ppp(A2′p),A‐dependent nuclease in reticulocyte lysates at the same concentration as ppp(A2′p)3A. The biological activity of these molecules may reflect their conversion to ppp(A2′p)nA. NAD+ is a preferred primer for the ppp(A2′p)nA synthetase in HeLa extracts. Despite this, using thc radiobinding assay in combination with high‐performance liquid chromatographic analysis, no evidence was found for the natural occurrence of NAD+2′p5′A2′p5′A or the corresponding A5′p45′A or ADP‐ribose derivatives in trichloroacetic acid/ether extracts froin interferon‐treated, encephalomyocarditis‐virus‐infected mouse L cells. In contrast ppp(A2′p)2A and ppp(A2′p)3A were detected at levels corresponding to approximately 100 nM in these cells. It appears therefore that none of the derivatives of NAD+ A5′p45′A and ADP‐ribose having two or more additional AMP residues in 2′‐5′ linkage, occurs naturally in these cells at concentrations ≥ 5 nM under conditions in which the ppp(A2′p)nA synthetase is actively synthesising ppp(A2′p)nA.

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Section: Synthesis and Purfication Of Ppp(a2'pla Analoguescontrasting

confidence: 96%

Section: Synthesis and Purfication Of Ppp(a2'pla Analoguesmentioning

confidence: 99%

Synthesis, Characterisation and Biological Significance of (2′‐5′)Oiigoadenylate Derivatives of NAD⁺, ADP‐Ribose and Adenosine(5′)Tetraphosph0(5′)Adenosine

Cayley

Kerr

1982

European Journal of Biochemistry

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“…2-5A synthetase is a nonprocessive enzyme, as evidenced by the formation of a series of 2Ј,5Ј-oligoadenylates of the formula, 2Ј,5Ј-A(pA) n in which n Ն 1 (10,11). Two nucleotide binding sites on 2-5A synthetase have been suggested as requirements for formation of 2-5A, i.e.…”

Section: Interferon (Ifn)mentioning

confidence: 99%

“…The donor site binds ATP, 2-5A, NAD ϩ , or other nucleotides with AMP moieties (10 -12). The acceptor site binds ATP, thereby providing the substrate for 2Ј-adenylation (10,11). Kinetic studies suggest a high affinity (K d ϭ 9 M) and a lower affinity (K d ϭ 1000 M) binding site (12).…”

Section: Interferon (Ifn)mentioning

confidence: 99%

Identification of the ATP Binding Domain of Recombinant Human 40-kDa 2′,5′-Oligoadenylate Synthetase by Photoaffinity Labeling with 8-Azido-[α-32P]ATP

Kon

Suhadolnik

1996

Journal of Biological Chemistry

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Three isoforms of the interferon-inducible 2,5-oligoadenylate (2-5A) synthetase that require doublestranded RNA have been isolated and cloned. However, identification of the amino acid(s) of 2-5A synthetase directly interacting with ATP is crucial to the elucidation of the mechanism of the enzymatic conversion of ATP to 2,5-oligoadenylates by 2-5A synthetase. Recombinant human 40-kDa 2-5A synthetase has been expressed as a glutathione S-transferase fusion protein in

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“…DISCUSSION The natural occurrence of (2'-5')A was established in interferon-treated and interferon-treated EMCV-or mengovirus-infected L cells (9,21,23), reovirus-infected (24) or EMCV-infected (25) interferon-treated Hela cells, and in Hela cell nuclei (12); here we clearly demonstrate its presence, mainly as trimer and tetramer, in rat liver cells. In spite of the (2'-5')A synthetase capacity to add p5'A2'p5'A to several substrates such as NAD+, ADP-ribose, and (A5'p)45'A in vitro (26,27), such derivatives were not detected in extracts of interferon-treated EMCV-infected mouse L cells (21,28). These analogues displace the radioactive probe in the RB assay at the same concentration as does (2'-5')A (28), but they do not activate the endonuclease activity except for the (A5'p)45'A derivatives.…”

Section: Resultsmentioning

confidence: 99%

(2'-5')Oligoadenylate in rat liver: modulation after partial hepatectomy.

Etienne-Smekens¹,

Vandenbussche²,

Dumont³

1983

Proc. Natl. Acad. Sci. U.S.A.

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(2'-5')Oligoadenylate synthetase [(2'-5')A synthetase], which synthesizes a series of oligoadenylates ppp-(A2'p)n5'A [collectively referred to as (2'-5')A], has been described previously in rat liver cells, where its concentration varied with the growth status of this organ--i.e., it decreased during the early phase of rat liver regeneration after partial hepatectomy. Because double-stranded RNA, the only known activator of this enzyme, has been detected in rat liver nuclei, (2'-5')A synthesis could occur in this tissue in vivo. Analysis of rat liver cell extract after HPLC by the endonuclease-based radiobinding assay revealed several components with retention times similar to (2'-5')A trimer- and tetramer-like material. A further characterization of these compounds by their susceptibility to alkaline phosphatase and snake venom phosphodiesterase, their resistance to micrococcal nuclease, and their ability to activate an endonuclease indicated the natural occurrence of oligonucleotides indistinguishable from authentic (2'-5')A in rat liver cells. Using the combination of the radiobinding assay and a simplified (2'-5')A extraction procedure that does not involve HPLC, we further show that the early drop of (2'-5')A synthetase activity during rat liver regeneration was accompanied by a similar decrease in intracellular (2'-5')A concentration. The three characteristic phases of the (2'-5')A synthetase kinetics during the first 40 hr of liver regeneration were mimicked by the kinetics of the synthesis of the (2'-5')A oligonucleotides themselves: between 6 and 20 hr after hepatectomy, there was a sharp decrease in (2'-5')A concentration; between 20 and 24 hr, the concentration of (2'-5')A reached a minimum; at 36 hr or after the first wave of DNA synthesis (the major event of liver regeneration), the (2'-5')A concentration returned to normal. In this characterization of the (2'-5')A oligonucleotide family in a functional tissue of an animal that had not been previously treated with interferon or infected with virus, the data are compatible with a physiological role of the (2'-5')A system acting as an intracellular component of the regulatory mechanisms leading to cell proliferation or differentiation.

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The 2′5′ oligoadenylate synthetase has a multifunctional 2′5′ nucleotidyl-transferase activity

Cited by 42 publications

References 21 publications

Synthesis, Characterisation and Biological Significance of (2′‐5′)Oiigoadenylate Derivatives of NAD⁺, ADP‐Ribose and Adenosine(5′)Tetraphosph0(5′)Adenosine

Synthesis, Characterisation and Biological Significance of (2′‐5′)Oiigoadenylate Derivatives of NAD⁺, ADP‐Ribose and Adenosine(5′)Tetraphosph0(5′)Adenosine

Identification of the ATP Binding Domain of Recombinant Human 40-kDa 2′,5′-Oligoadenylate Synthetase by Photoaffinity Labeling with 8-Azido-[α-32P]ATP

(2'-5')Oligoadenylate in rat liver: modulation after partial hepatectomy.

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The 2′5′ oligoadenylate synthetase has a multifunctional 2′5′ nucleotidyl-transferase activity

Cited by 42 publications

References 21 publications

Synthesis, Characterisation and Biological Significance of (2′‐5′)Oiigoadenylate Derivatives of NAD+, ADP‐Ribose and Adenosine(5′)Tetraphosph0(5′)Adenosine

Synthesis, Characterisation and Biological Significance of (2′‐5′)Oiigoadenylate Derivatives of NAD+, ADP‐Ribose and Adenosine(5′)Tetraphosph0(5′)Adenosine

Identification of the ATP Binding Domain of Recombinant Human 40-kDa 2′,5′-Oligoadenylate Synthetase by Photoaffinity Labeling with 8-Azido-[α-32P]ATP

(2'-5')Oligoadenylate in rat liver: modulation after partial hepatectomy.

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Synthesis, Characterisation and Biological Significance of (2′‐5′)Oiigoadenylate Derivatives of NAD⁺, ADP‐Ribose and Adenosine(5′)Tetraphosph0(5′)Adenosine

Synthesis, Characterisation and Biological Significance of (2′‐5′)Oiigoadenylate Derivatives of NAD⁺, ADP‐Ribose and Adenosine(5′)Tetraphosph0(5′)Adenosine