Stimulation by nitric oxide of an NAD linkage to glyceraldehyde-3-phosphate dehydrogenase.

McDonald, Lee J.; Moss, Joel

doi:10.1073/pnas.90.13.6238

Cited by 214 publications

(102 citation statements)

References 27 publications

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“…GAPDH (Fig. 10B), however, was labeled by both [adenine-U- 14 C]NAD and [carbonyl- 14 C]NAD, consistent with the attachment of NAD, not just ADP-ribose, as previously reported (29). ART5, therefore, was auto-ADP-ribosylated, not modified by NAD.…”

Section: C-nad and Masssupporting

confidence: 87%

Modification of the ADP-ribosyltransferase and NAD Glycohydrolase Activities of a Mammalian Transferase (ADP-ribosyltransferase 5) by Auto-ADP-ribosylation

Weng¹,

Thompson²,

Kim³

et al. 1999

Journal of Biological Chemistry

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Mono-ADP-ribosylation, a post-translational modification in which the ADP-ribose moiety of NAD is transferred to an acceptor protein, is catalyzed by a family of amino acid-specific ADP-ribosyltransferases. ADP-ribosyltransferase 5 (ART5), a murine transferase originally isolated from Yac-1 lymphoma cells, differed in properties from previously identified eukaryotic transferases in that it exhibited significant NAD glycohydrolase (NADase) activity. To investigate the mechanism of regulation of transferase and NADase activities, ART5 was synthesized as a FLAG fusion protein in Escherichia coli. Agmatine was used as the ADP-ribose acceptor to quantify transferase activity. ART5 was found to be primarily an NADase at 10 M NAD, whereas at higher NAD concentrations (1 mM), after some delay, transferase activity increased, whereas NADase activity fell. This change in catalytic activity was correlated with auto-ADP-ribosylation and occurred in a time-and NAD concentration-dependent manner. Based on the change in mobility of auto-ADP-ribosylated ART5 by SDS-polyacrylamide gel electrophoresis, the modification appeared to be stoichiometric and resulted in the addition of at least two ADP-ribose moieties. Auto-ADP-ribosylated ART5 isolated after incubation with NAD was primarily a transferase. These findings suggest that auto-ADP-ribosylation of ART5 was stoichiometric, resulted in at least two modifications and converted ART5 from an NADase to a transferase, and could be one mechanism for regulating enzyme activity.Mono-ADP-ribosylation is a post-translational modification of proteins catalyzed by enzymes that transfer the ADP-ribose moiety of NAD to specific amino acids in protein acceptors (1, 2). The best characterized mono-ADP-ribosylation reactions are those catalyzed by bacterial toxin ADP-ribosyltransferases such as cholera (3), diphtheria (4), and pertussis (5) toxins, which alter critical metabolic and regulatory pathways. For example, cholera toxin ADP-ribosylates an arginine in the ␣-subunit of the stimulatory heterotrimeric guanine nucleotidebinding protein (G protein), resulting in the activation of adenylyl cyclase and an increase in intracellular cyclic AMP (3).Mono-ADP-ribosyltransferase activity specific for arginine has been detected in numerous animal tissues (2, 6 -14). Transferases have been cloned from rabbit (7) and human (8) skeletal muscle, chicken polymorphonuclear granulocytes (9) and nucleoblasts (10), and mouse lymphoma cell lines Yac-1 (12, 13) and SL12 (16). Based on immunological, biochemical, and sequence analysis, it appears that the transferase, termed ART1, is glycosylphosphatidylinositol (GPI) 1 -anchored to the cell surface (8, 12). Consistent with its extracellular location, a GPIlinked muscle transferase in C2C12 mouse myotubes ADPribosylates integrin ␣7 (17). Inhibitor studies suggest that the muscle transferase may participate in the regulation of myogenesis (18).GPI-anchored transferases were found also in mouse cytotoxic T lymphocytes (CTL) and some murine T cell lymphoma and h...

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Section: C-nad and Masssupporting

confidence: 87%

Modification of the ADP-ribosyltransferase and NAD Glycohydrolase Activities of a Mammalian Transferase (ADP-ribosyltransferase 5) by Auto-ADP-ribosylation

Weng¹,

Thompson²,

Kim³

et al. 1999

Journal of Biological Chemistry

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“…None of the treatments described under "Results and Discussion" affected the amount of protein recovered on the filter. As previously reported (15,16), GAPDH is nonenzymatically mono-ADPribosylated in the absence of BFA. Thus, for each condition tested in this study, control experiments using the BFA vehicle (dimethyl sulfoxide) were carried out to evaluate the basal nonenzymatic ADP-ribosylation of GAPDH.…”

Section: Adp-ribosylationsupporting

confidence: 84%

Characterization of Chemical Inhibitors of Brefeldin A-activated Mono-ADP-ribosylation

Weigert

Colanzi

Mirоnоv

et al. 1997

Journal of Biological Chemistry

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Brefeldin A, a toxin inhibitor of vesicular traffic, induces the selective mono-ADP-ribosylation of two cytosolic proteins, glyceraldehyde-3-phosphate dehydrogenase and the novel GTP-binding protein BARS-50. Here, we have used a new quantitative assay for the characterization of this reaction and the development of specific pharmacological inhibitors. Mono-ADP-ribosylation is activated by brefeldin A with an EC 50 of 17.0 ؎ 3.1 g/ml, but not by biologically inactive analogs including a brefeldin A stereoisomer. Brefeldin A acts by increasing the V max of the reaction, whereas it does not influence the K m of the enzyme for NAD ؉ (154 ؎ 13 M). The enzyme is an integral membrane protein present in most tissues and is modulated by Zn 2؉ , Cu 2؉ , ATP (but not by other nucleotides), pH, temperature, and ionic strength. To identify inhibitors of the reaction, a large number of drugs previously tested as blockers of bacterial ADPribosyltransferases were screened. Two classes of molecules, one belonging to the coumarin group (dicumarol, coumermycin A 1 , and novobiocin) and the other to the quinone group (ilimaquinone, benzoquinone, and naphthoquinone), rather potently and specifically inhibited brefeldin A-dependent mono-ADP-ribosylation. When tested in living cells, these molecules antagonized the tubular reticular redistribution of the Golgi complex caused by brefeldin A at concentrations similar to those active in the mono-ADP-ribosylation assay in vitro, suggesting a role for mono-ADP-ribosylation in the cellular actions of brefeldin A.Mono-ADP-ribosylation is a post-translational modification of proteins whereby the adenosine 5Ј-diphosphoribose moiety of NAD ϩ is transferred to one of a number of amino acid residues (1, 2). Several well characterized mono-ADP-ribosylation reactions are catalyzed by bacterial toxins and result in the permanent modification of GTPases with key regulatory functions in cellular processes (1, 2). Similar reactions are also catalyzed by eukaryotic enzymes, but their cellular significance, despite recent advances (3-5), is less well understood. Recently, we have reported that brefeldin A (BFA), 1 a fungal toxin metabolite of palmitic acid (6) with potent inhibitory effects on intracellular membrane traffic (7), stimulates the selective mono-ADP-ribosylation of two cytosolic proteins of 38 and 50 kDa in mammalian cells (8). The 50-kDa substrate (BARS-50; see Ref. 9) binds GTP and is regulated by ␤␥-subunits of trimeric G proteins; it has therefore been proposed to be a novel G protein involved in membrane transport (9). The p38 substrate is glyceraldehyde-3-phosphate dehydrogenase (GAPDH), a multifunctional protein involved in several cellular processes (10 -16). These observations have raised the question as to whether some of the cellular effects of BFA might be mediated by mono-ADP-ribosylation.The cellular actions of BFA are multiple and complex. BFA selectively blocks constitutive protein secretion and causes a rapid and extensive disruption of the Golgi apparatus consisting of the ...

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“…Hydrolysis of these products with NaOH demonstrated however that the 32 P-labelled products were NAD-protein adducts. Similar reactions between NAD + and proteins (in the absence or presence of nitric oxide donors) have been described previously (Boyd et al, 1993, McDonald & Moss 1993.…”

Section: Discussionmentioning

confidence: 57%

Inhibition of chemotaxis in A7r5 rat smooth muscle cells by a novel panel of inhibitors

Saxty

Yadollahi-Farsani

Kefalas

et al. 1998

British J Pharmacology

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1 Arginine-speci®c ADP-ribosyltransferase (ART) activity has been implicated in white cell chemotaxis. In this study, we examined the capacity of a panel of structurally unrelated inhibitors and pseudosubstrates of ART to inhibit chemotaxis of A7r5 rat vascular smooth muscle cells in response to PDGF-BB. 2 The IC 50 values for nicotinamide (12 mM) and novobiocin (165 mM) were similar to those observed for inhibition of chemotaxis by human polymorphonuclear neutrophil leucocytes (PMN), whereas vitamins K 3 (IC 50 =22 mM) and K 1 (IC 50 =95 mM) were less potent than previously described in PMNs. The pseudo-substrates for the enzyme (DEA-BAG, agmatine and arginine-methylester) also inhibited A7r5 chemotaxis, and in addition inhibited cell adhesion at similar concentrations. Vitamin K 3 was unique among the inhibitors of ART, in that it also inhibited cell adhesion. 3 A rat ART1 transcript was ampli®ed by rtPCR from rat skeletal muscle, and was noted to share 94% homology with the mouse ART1 cDNA sequence. No such transcript could be detected in A7r5 cells by Northern blot analysis or rtPCR. 4 Evidence for ART activity on the surface of A7r5 cells was investigated using These results indicated that the labelled proteins were adducts with NAD + , and not the products of ART activity. The absence of ART catalytic activity in A7r5 cells was con®rmed in protocols designed to show ADP-ribosylation of agmatine. 5 We conclude that the chemotactic activity of A7r5 cells is independent of ART activity, and the mechanism whereby the novel panel of inhibitors reduced cell migration remains unde®ned.

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Stimulation by nitric oxide of an NAD linkage to glyceraldehyde-3-phosphate dehydrogenase.

Cited by 214 publications

References 27 publications

Modification of the ADP-ribosyltransferase and NAD Glycohydrolase Activities of a Mammalian Transferase (ADP-ribosyltransferase 5) by Auto-ADP-ribosylation

Modification of the ADP-ribosyltransferase and NAD Glycohydrolase Activities of a Mammalian Transferase (ADP-ribosyltransferase 5) by Auto-ADP-ribosylation

Characterization of Chemical Inhibitors of Brefeldin A-activated Mono-ADP-ribosylation

Inhibition of chemotaxis in A7r5 rat smooth muscle cells by a novel panel of inhibitors

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