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

Etienne-Smekens, M.; Vandenbussche, Pierre-Yves; Dumont, Jacques Emile

doi:10.1073/pnas.80.15.4609

Cited by 54 publications

(15 citation statements)

References 38 publications

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“…The activity of ppp(A2'p), synthetase parallels the intracellular level of ppp(A2'p). [28]. These results suggest that interferon acts on the liver to increase the level of ppp(A2'p).…”

Section: Discussionmentioning

confidence: 71%

Inhibition of ornithine decarboxylase induction of interferon (α+β) and its reversal by dibutyryl adenosine 3′, 5′‐monophosphate

Nishiguchi

Otani²,

Matsui‐Yuasa³

et al. 1988

European Journal of Biochemistry

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Interferon (α+β) given to C3H/HeN mice intraperitoneally inhibited increases in the activities of adenylate cyclase and ornithine decarboxylase after partial hepatectomy. The inhibition of ornithine decarboxylase was prevented by administration of dibutyryl CAMP. Core (2′‐5′)oligo(adenylate), i.e. A2′p5′A2′p5′A or (A2′P)2A, as well as interferon inhibited the increases in these two enzymes caused by partial hepatectomy. The inhibition by (A2′p)2A of ornithine decarboxylase activity was reversed by dibutyryl CAMP. These results suggested that the activity of interferon was similar to that of (A2′p)2A and that the inhibition of ornithine decarboxylase induction caused by these agents resulted from the inhibition of adenylate cyclase activity.

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“…The activity of ppp(A2'p), synthetase parallels the intracellular level of ppp(A2'p). [28]. These results suggest that interferon acts on the liver to increase the level of ppp(A2'p).…”

Section: Discussionmentioning

confidence: 71%

Inhibition of ornithine decarboxylase induction of interferon (α+β) and its reversal by dibutyryl adenosine 3′, 5′‐monophosphate

Nishiguchi

Otani²,

Matsui‐Yuasa³

et al. 1988

European Journal of Biochemistry

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“…Thus, it is conceivable that the 9-2 protein is used for tissue remodeling in interferon-unrelated physiological regulations. It is pertinent in this context to note that very high levels of 2-5(A) synthetase are expressed in resorbing chick oviducts (27) and partially hepatectomized livers (28). FIG.…”

Section: Resultsmentioning

confidence: 99%

A Specific Isozyme of 2′-5′ Oligoadenylate Synthetase Is a Dual Function Proapoptotic Protein of the Bcl-2 Family

Ghosh

Sarkar

Rowe

et al. 2001

Journal of Biological Chemistry

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2-5(A) synthetases are a family of interferon-induced enzymes that polymerize ATP into 2-5 linked oligoadenylates that activate RNase L and cause mRNA degradation. Because they all can synthesize 2-5(A), the reason for the existence of so many synthetase isozymes is unclear. Here we report that the 9-2 isozyme of 2-5(A) synthetase has an additional activity: it promotes apoptosis in mammalian cells. The proapoptotic activity of 9-2 was isozyme-specific and enzyme activity-independent. The 9-2-expressing cells exhibited many properties of cells undergoing apoptosis, such as DNA fragmentation, caspase activation, and poly ADP-ribose polymerase and lamin B cleavage. The isozyme-specific carboxyl-terminal tail of the 9-2 protein was shown, by molecular modeling, to contain a Bcl-2 homology 3 (BH3) domain, suggesting that it may be able to interact with members of the Bcl-2 family that contain BH1 and BH2 domains. Co-immunoprecipitate assays and confocal microscopy showed that 9-2 can indeed interact with the anti-apoptotic proteins Bcl-2 and Bclx L in vivo and in vitro. Mutations in the BH3 domain that eliminated the 9-2-Bcl-2 amd 9-2-Bclx L interactions also eliminated the apoptotic activity of 9-2. Thus, we have identified an interferon-induced dual function protein of the Bcl-2 family that can synthesize 2-5(A) and promote cellular apoptosis independently. Moreover, the cellular abundance of this protein is regulated by alternative splicing; the other isozymes encoded by the same gene are not proapoptotic.

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“…The immunoblot analyses with the anti-peptide B antibodies to (2'-5')OASE ( Fig. 1) and direct assays of the enzyme's activity show that the (2'-5')OASE proteins (12,13) and activity (19,20) reside in both the nuclear and cytoplasmic preparations of non-IFN-induced HeLa cells. The immunoblots reveal the presence of (2'-5')OASE species of 40 and 100 kDa in HeLa nuclear extracts (lane 7) and in nuclear RNP extracts of HeLa nuclei enriched with large nuclear RNP particles (21-23) (lane 5).…”

Section: Methodsmentioning

confidence: 99%

Possible involvement of (2'5')oligoadenylate synthetase activity in pre-mRNA splicing.

Sperling

Chebath

Arad-Dann

et al. 1991

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

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The first step in splicing of pre-mRNA involves an intermediate lariat structure, in which a 2'-5' phosphodiester bond between the 5' terminal guanosine residue of the intron and a specific adenosine residue near the 3' end of the intron is formed. A mammalian enzyme that generates 2'-5' phosphodiester bonds is (2'-5')oligoadenylate synthetase [(2'-5')OASE]. Although the expression of this enzyme is induced by interferon, low constitutive levels can be detected in untreated cells and tissues. The structural similarity between the lariat branch point and the 2'-5' phosphodiester bond generated by (2'-5')OASE prompted the experiments described here which suggest that this enzyme is involved in pre-mRNA splicing. (i) We show that a (2'-5')OASE activity is associated with 60S spliceosomes in an ATP-and RNA-dependent manner and that it can be indirectly immunoprecipitated by anti-Sm antibodies. (ii) Antibodies against (2'-5')OASE inhibit the lariat formation in the first step of splicing when added directly to a splicing reaction in vitro. (iii) HeLa cell nuclear extracts immunodepleted of (2'-5')OASE activity were also deficient in splicing activity.Splicing of pre-mRNA occurs in a multicomponent ribonucleoprotein (RNP) complex, designated the spliceosome, in an apparent two-step mechanism. The first event is cleavage at the 5' splice site with concomitant formation of a lariat structure involving the intron and the 3' exon. In the second step, the two exons are ligated and the intron is released in a lariat form (for reviews, see refs. 1-3).In the lariat configuration, the 5'-terminal guanosine residue of the intron is covalently joined by a 2'-5' phosphodiester bond to a specific and highly conserved adenosine residue near the 3' end of the intron (1-3). The discovery of several catalytically active RNA molecules, particularly those involved in the self-splicing of group II introns, has led to the hypothesis that mammalian nuclear pre-mRNA splicing is also a reaction catalyzed by RNA (for review, see ref. 4). Nonetheless, no evidence has yet been provided to support this proposal. On the other hand, no proteinmediated catalytic activity has yet been implicated in splicing of pre-mRNA. A mammalian enzyme that generates 2'-5' phosphodiester bonds is (2'-5')oligoadenylate synthetase [(2'-5')OASE] (5-7). The expression of (2'-5')OASE is enhanced in cells treated with interferon (IFN) (5,8,9); however, low constitutive levels of the enzyme can be detected in untreated cells and tissues (10, 11). The structural similarity between the lariat branch point and the (2'-5')oligoadenylate molecule, with respect to occurrence of a 2'-5' phosphodiester bond in both, raised the possibility that a (2'-5')OASE activity is involved in pre-mRNA splicing. Here we provide experimental evidence to support this hypothesis. MATERIALS AND METHODSAntibodies. Anti-(2'-5')OASE antibodies used were as follows. Anti-peptide B antibody was elicited in rabbits against a synthetic peptide (peptide B) that is common to the 40-and 46-kDa fo...

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

Cited by 54 publications

References 38 publications

Inhibition of ornithine decarboxylase induction of interferon (α+β) and its reversal by dibutyryl adenosine 3′, 5′‐monophosphate

Inhibition of ornithine decarboxylase induction of interferon (α+β) and its reversal by dibutyryl adenosine 3′, 5′‐monophosphate

A Specific Isozyme of 2′-5′ Oligoadenylate Synthetase Is a Dual Function Proapoptotic Protein of the Bcl-2 Family

Possible involvement of (2'5')oligoadenylate synthetase activity in pre-mRNA splicing.

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