Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.4.2.30 (PARP)
13,611 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We investigated the effect on the Ca2+-dependent ATPase activity of ADP-ribosylation of the enzyme from the rabbit skeletal muscle sarcoplasmic reticulum. A reconstituted ADP-ribosylation system of Ca2+-dependent ATPase in which the enzyme and ADP-ribosyltransferase, both were partially purified from the vesicles, and poly L-lysine were contained, was preincubated with 1 mM NAD, and the Ca2+-dependent ATPase activity was assayed. The NAD-dependent suppression of the enzyme activity depended on both the concentration of NAD and preincubation-time for the ADP-ribosylation, and was reversed by adding 20 mM arginine during the preincubation. These results taken together with the findings that Ca2+-dependent ATPase is a major acceptor protein for the modification in rabbit skeletal muscle sarcoplasmic reticulum [Hara et al. (1987) Biochem. Biophys. Res. Commun. 144; 856-862] suggest that Ca2+-transport in the sarcoplasmic reticulum may be regulated through changes in the rate of ADP-ribosylation of Ca2+-dependent ATPase.
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PMID:ADP-ribosylation of Ca2+-dependent ATPase in vitro suppresses the enzyme activity. 296 35

Sarcolemmal membranes were isolated from porcine skeletal muscle by modifications of a LiBr-extraction technique. Latency determinations of acetylcholinesterase, ouabain-sensitive p-nitrophenylphosphatase, [3H]ouabain binding, and (Na+ + K+)-ATPase activities indicated that 65-76% of the membranes were sealed inside-out vesicles. The preparations were enriched in cholesterol and phospholipid, and demonstrated adenylate cyclase activity and both cAMP and cGMP phosphodiesterase activities. An indication of the purity of this fraction was that the Ca2+-ATPase activity (0.13 mumol Pi mg-1 min-1 at 37 degrees C) was 3.8% of that of porcine skeletal muscle sarcoplasmic reticulum preparations. Pertussis toxin specifically catalyzed the ADP-ribosylation of a Mr 41,000 sarcolemmal protein, indicating the presence of the inhibitory guanine nucleotide regulatory protein of adenylate cyclase, Ni. An endogenous ADP-ribosyltransferase activity, with several membrane protein substrates, was also demonstrated. The addition of exogenous cAMP-dependent protein kinase or calmodulin promoted the phosphorylation of a number of sarcolemmal proteins. The calmodulin-dependent phosphorylation exhibited an approximate K 1/2 for Ca2+ of 0.5 microM, and an approximate K 1/2 for calmodulin of 0.1 microM. 125I-Calmodulin affinity labeling of the sarcolemma, using dithiobis(succinimidyl propionate), demonstrated the presence of Mr 160,000 and 280,000 calmodulin-binding components in these membranes. These results demonstrate that this porcine preparation will be valuable in the study of skeletal muscle sarcolemmal ion transport, protein and hormonal receptors, and protein kinase-catalyzed phosphorylation.
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PMID:Components of purified sarcolemma from porcine skeletal muscle. 299 26

We reported previously on ADP-ribosylation of actins by chicken arginine-specific ADP-ribosyltransferase in vitro and in situ and the inhibition of actin polymerization by this modification [Terashima, M., Mishima, K., Yamada, K., Tsuchiya, M., Wakutani, T. & Shimoyama, M. (1992) Eur. J. Biochem. 204, 305-311]. In the present study, we determined amino acid residues of ADP-ribosylation site(s) in globular (G-) and filamentous (F-) actins and examined the molecular basis of the modification of actin. Arginine-specific ADP-ribosylation occurred at Arg28 and Arg206 in G-actin, but only at Arg28 in F-actin. ADP-ribosylation of Arg206, located on the pointed end of the actin molecule, significantly blocked the interaction with deoxyribonuclease I. These results indicate that Arg206 in G-actin may be involved in actin polymerization. ADP-ribosylation of Arg28, located on the outer surface of actin molecule, did not affect the binding activity with myosin subfragment-1, that is thought to interact through the N-terminal amino acid residues of G-actin. ADP-ribosylation at both Arg28 and Arg206 of G-actin had no apparent effect on the intrinsic ATPase activity. We concluded from this study that ADP-ribosylation of Arg206 in G-actin causes the inhibition of actin polymerization, and that ADP-ribosylation of Arg28 occurs in F-actin.
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PMID:ADP-ribosylation of Arg28 and Arg206 on the actin molecule by chicken arginine-specific ADP-ribosyltransferase. 762 77

Turkey erythrocyte ADP-ribosyltransferase A catalyzes the transfer of ADP-ribose from NAD to both monomeric and polymeric skeletal muscle alpha-actin with the incorporation of 2 mol of ADP-ribose per mol of actin. In contrast, Clostridium perfringens iota toxin ADP-ribosylates only G-actin, with modification at arginine-177 [Vandekerckhove, J., et al. (1987) FEBS Lett. 255, 48-42]. Transferase A-catalyzed modifications are sensitive to 0.5 M neutral hydroxylamine, consistent with the arginine side chain modification. Radiolabeled peptides ADP-ribosylated by transferase A were generated by tryptic digestion and purified by reversed phase high-performance liquid chromatography. Amino acid sequence and molecular mass analysis identified the ADP-ribosylation sites as Arg-95 and Arg-372 of actin; both residues are located within subdomain-1 of the actin 3D structure [Kabsch, W., et al. (1990) Nature 347, 37-44]. ADP-ribosylation did not affect cytochalasin D-stimulated G-actin ATPase, the binding of actin to DNase I or to gelsolin, or the ability of actin to polymerize. Following ADP-ribosylation, however, a prolonged delay in polymerization was observed, consistent with a decreased rate of nucleation.
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PMID:ADP-ribosyltransferase type A from turkey erythrocytes modifies actin at Arg-95 and Arg-372. 781 15

We compared acceptor-protein specificities on the formation of ADP-ribose.acceptor adducts by arginine-specific ADP-ribosyltransferase (EC 2.4.2.31) purified from rabbit skeletal muscle sarcoplasmic reticulum (SR) with those of the enzyme purified from chicken peripheral polymorphonuclear cells (heterophils). Major differences are as follows: (1), p33 and beta/gamma-actin, preferential endogenous acceptor proteins for the modification by the heterophil enzyme (Mishima, K., Terashima, M., Obara, S., Yamada, K., Imai, K and Shimoyama, M. (1991) J. Biochem. 110, 388-394 and Terashima, M., Mishima, K., Yamada, K., Tsuchiya, M., Wakutani, T. and Shimoyama, M. (1992) Eur. J. Biochem. 204, 305-311) were not modified by the SR enzyme. (2), The modification of p33 by the heterophil enzyme was enhanced by addition of polyanions such as DNA while the protein did not function as acceptor for modification by the SR enzyme even in the presence of DNA. (3), To ADP-ribosylate endogenous substrate Ca(2+)-transporting ATPase (EC 3.6.1.38) of rabbit skeletal muscle SR, the SR ADP-ribosyltransferase required polycations such as poly(L-lysine), whereas the heterophil enzyme modified the ATPase in the absence of poly(L-lysine). These results suggest that vertebrate arginine-specific ADP-ribosyltransferase prefers its own acceptor protein for the modification. Some other properties of the SR and the heterophil ADP-ribosyltransferases were also compared.
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PMID:Comparison of acceptor protein specificities on the formation of ADP-ribose.acceptor adducts by arginine-specific ADP-ribosyltransferase from rabbit skeletal muscle sarcoplasmic reticulum with those of the enzyme from chicken peripheral polymorphonuclear cells. 843 75

We have isolated an ADP-ribosylation factor (ARF) gene from the human malarial parasite, Plasmodium falciparum. The gene (P. falciparum arf1) has four introns and the exons encode a protein of 181 amino acids with high similarity to the mammalian class I ARF proteins 1-3 (> or = 74% amino acid identity). Southern hybridization suggests there is at least one additional arf in the P. falciparum genome. Northern analysis identified a single P. falciparum arf1 mRNA of 1.8 kb in the asexual blood stage form of the parasite. The P. falciparum arf1 mRNA levels are developmentally regulated, reaching a maximum during nuclear division towards the end of the intraerythrocytic cycle. P. falciparum arf1 cDNA was isolated by reverse-transcriptase polymerase chain reaction and used to express a recombinant protein in Escherichia coli. Recombinant P. falciparum ARF1 protein was purified with stoichiometric amounts of bound GDP, although intrinsic guanose triphosphatase activity of the protein could not be detected. The protein stimulated cholera-toxin-catalyzed ADP-ribosyltransferase activity in a reaction that was dependent upon the addition of both dimyristoylglycerophosphocholine and cholate. The protein bound GTP with first-order kinetics with an apparent rate constant, k', of 0.0145 (+/- 0.0019) min-1. These results suggest that P. falciparum ARF1 is a member of the class 1 ARF family and provide additional evidence for the existence of a classical secretory pathway in P. falciparum.
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PMID:Isolation, expression and characterization of the gene for an ADP-ribosylation factor from the human malaria parasite, Plasmodium falciparum. 895 60

Effects of ADP-ribosylation of skeletal muscle alpha-actin by Clostridium perfringens iota toxin and by turkey erythrocyte ADP-ribosyltransferase A on profilin-regulated nucleotide exchange and ATPase activity were compared. ADP-ribosylation of actin at Arg 177 by Clostridium perfringens iota toxin increased the nucleotide dissociation rate from 2.2 x 10(-3) s-1 to 4.5 x 10(-3) s-1 without affecting the profilin-induced stimulation of nucleotide exchange. In contrast, ADP-ribosylation of actin at Arg95/Arg372 induced by turkey erythrocyte transferase decreased the nucleotide dissociation rate to 1.5 x 10(3) s-1 and inhibited the profilin-induced stimulation of nucleotide exchange. Whereas toxin-induced ADP-ribosylation at Arg177 blocked actin ATPase, basal G-actin ATPase was not altered by ADP-ribosylation at Arg95/Arg372 but inhibited profilin effects on actin ATPase.
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PMID:ADP-ribosylation of actin by Clostridium perfringens iota toxin and turkey erythrocyte ADP-ribosyltransferase A: effects on profilin-regulated nucleotide exchange and ATPase activity. 897 27

The requirement for caspases (ICE-like proteases) were investigated in mediating apoptosis of WEHI7.2 mouse lymphoma cells in response to two death inducers with different mechanisms of action, the glucocorticoid hormone dexamethasone (DX) and the calcium-ATPase inhibitor thapsigargin (TG). Apoptosis induction by these agents followed different kinetics, and was closely correlated with in vivo activation of caspase-3 (CPP32/Yama/Apopain) and cleavage of the caspase target protein poly(ADP-ribose) polymerase (PARP). Caspase activation and PARP cleavage were inhibited by Bcl-2 overexpression. Cell extracts from DX- and TG-treated cells cleaved the in vitro synthesized baculovirus p35 ICE-like protease target, producing 25 and 10 kDa fragments. p35 cleavage was inhibited by mutating the active site aspartic acid to alanine, and by a panel of protease inhibitors that inhibit caspase-3-like proteases, including iodoacetamide, N-ethylmaleimide, and Ac-DEVD-cho. Treatment of cells in vivo with two cell permeant peptide fluoromethylketone inhibitors of caspase activity, Z-VAD-fmk and Z-DEVD-fmk, inhibited DX- and TG-induced apoptotic nuclear changes and maintained plasma membrane integrity, whereas the cathepsin inhibitor, Z-FA-fmk, and two calpain inhibitors failed to inhibit apoptosis. An unexpected observation was that due to the delayed time course of DX-induced apoptosis, optimal preservation of plasma membrane integrity was achieved by adding caspase inhibitors beginning 8 h after DX addition. In summary, the findings indicate that two diverse apoptosis-inducing signals converge into a common Bcl-2-regulated pathway that leads to caspase activation and apoptosis.
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PMID:Apoptosis induction by the glucocorticoid hormone dexamethasone and the calcium-ATPase inhibitor thapsigargin involves Bc1-2 regulated caspase activation. 970 90

Werner syndrome (WS) is a genetic premature aging disorder in which patients appear much older than their chronological age. The gene mutated in WS encodes a nuclear protein (WRN) which possesses 3'-5' exonuclease and ATPase-dependent 3'-5' helicase activities. The genomic instability associated with WS cells and the biochemical characteristics of WRN suggest that WRN plays a role in DNA metabolic pathways such as transcription, replication, recombination and repair. Recently we have identified poly(ADP-ribose) polymerase-1 (PARP-1) as a new WRN interacting protein. In this paper, we further mapped the interacting domains. We found that PARP-1 bound to the N-terminus of WRN and to the C-terminus containing the RecQ-conserved (RQC) domain. WRN bound to the N-terminus of PARP-1 containing DNA binding and BRCA1 C-terminal (BRCT) domains. We show that unmodified PARP-1 inhibited both WRN exonuclease and helicase activities, and to our knowledge is the only known WRN protein partner that inactivates both of the WRN's catalytic activities suggesting a biologically significant regulation. Moreover, this dual inhibition seems to be specific for PARP-1, as PARP-2 did not affect WRN helicase activity and only slightly inhibited WRN exonuclease activity. The differential effect of PARP-1 and PARP-2 on WRN catalytic activity was not due to differences in affinity for WRN or the DNA substrate. Finally, we demonstrate that the inhibition of WRN by PARP-1 was influenced by the poly(ADP-ribosyl)ation state of PARP-1. The biological relevance of the specific modulation of WRN catalytic activities by PARP-1 are discussed in the context of pathways in which these proteins may function together, namely in the repair of DNA strand breaks.
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PMID:Poly(ADP-ribose) polymerase 1 regulates both the exonuclease and helicase activities of the Werner syndrome protein. 1529 49

Apicularen A, a macrolide isolated from the myxobacterial genus Chondromyces, suppressed the proliferation of human promyelocytic leukemia cells (HL-60 cells), increased the release of lactate dehydrogenase and induced condensation and fragmentation of chromatin at 1 to 100 nM. In addition, it induced the DNA fragmentation, increased the percentage of annexin V-stained cells, and cleaved poly(ADP-ribose) polymerase (PARP), a substrate of caspase. In contrast, apicularen B, an N-acetylglucosamine glycoside of apicularen A, had no such effects at 100 nM. These findings indicated that apicularen A induces apoptosis in HL-60 cells by activating caspases. Phosphorylation of p44/42 MAPK, p38 MAPK and Akt was not induced by apicularen A at 100 nM, suggesting that the apicularen A-induced apoptosis in HL-60 cells is not regulated by the activation of p44/42 MAPK, p38 MAPK or Akt. Furthermore, by acridine orange staining of the cells, it was suggested that apicularen A but not apicularen B inhibits vacuolar-type H+-ATPase.
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PMID:Induction of apoptosis by apicularen A in human promyelocytic leukemia cell line HL-60. 1585 5


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