Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Effects of P1,P4-bis(5'-adenosyl)tetraphosphate and its phosphonate analogs on the ADP-ribosylation of H1 catalyzed by bovine testis ADP-ribose polymerase was investigated. Analogs App[CH(COCH3)]ppA and Ap[CH2]pppA as well as Ap4A inhibited poly(ADP)-ribosylation of histone H1 and at the same time accepted the ADP-ribosyl moiety of NAD. It was shown that inhibition of ADP-ribosylation of histone H1 is due to the competition of nucleotides with histone H1 for accepting ADP-ribosyl moiety of NAD on the one hand, and alteration of acceptor properties of the histone H1 on the other.
Mol Biol (Mosk)
PMID:[Reaction of poly(ADP)-ribosylation of histone H1 in the presence of P1,P4-bis(5'-adenosyl)tetraphosphate and its phosphonate analogs]. 314 90

The effect of inhibiting poly(ADP-ribose) synthesis on DNA excision repair following UV irradiation of cultured normal human fibroblasts was determined under conditions which did not perturb NAD+ concentration. Following UV irradiation, there was a transient increase in DNA strand breaks to a maximum of 800 rad eq of breaks 30 min after damage. 3-Aminobenzamide (5 mM) caused a 50% increase in the maximum number of DNA single strand breaks following damage but did not prevent the decline in strand breaks which normally occurs within the first hour after damage. Addition of 3-aminobenzamide several hours after damage, when most of the strand breaks had disappeared, caused a reaccumulation of strand breaks. 3-Aminobenzamide inhibited ligation of repair patches, as measured by exonuclease III, following damage by UV radiation and the magnitude of the inhibition was sufficient to account for the increases in strand breaks caused by 3-aminobenzamide. UV radiation alone did not lower NAD+ concentrations; however, when the repair synthesis step was inhibited by aphidicolin and hydroxyurea, the number of single strand breaks increased and the NAD+ concentration fell to 11%. 3-Aminobenzamide inhibited this depletion of NAD+ by 80%.
Mol Pharmacol 1988 Mar
PMID:Inhibition of repair patch ligation by an inhibitor of poly(ADP-ribose) synthesis in normal human fibroblasts damaged with ultraviolet radiation. 335 98

In vitro ADP-ribosylation of chromosomal proteins and its modulation by spermine, 3-aminobenzamide (3-AB) and benzamide were studied by incubating the nuclei of cerebral hemisphere of 3-, 14- and 30-day old rats with 32P-NAD+. Histones get ADP-ribosylated more than the non-histone chromosomal (NHC) proteins. H1 is the major target for ADP-ribosylation. Among the nucleosomal histones, H2B is ADP-ribosylated most. The other core histones also get ADP-ribosylated to a lesser extent. ADP-ribosylation of both histones and NHC proteins decreases during development. Spermine stimulates, whereas 3-AB and benzamide inhibit, 32P-ADP-ribose incorporation into histones and NHC proteins. These effects decrease with development. Mild digestion of chromatin by micrococcal nuclease (MNase), EcoRI and AluI prior to ADP-ribosylation stimulates incorporation of 32P-ADP-ribose. The degree of stimulation decreases as development proceeds. Such alterations indicate progressive condensation of chromatin with development.
Mol Biol Rep 1986
PMID:In vitro ADP-ribosylation of chromosomal proteins of the brain of developing rats. 373 41

2',5'-Oligo(A)synthetase (2-5A) and 2-phosphodiesterase were found in the L cells nuclei. In the cell nuclei 2-5A is 10-30 times higher, than in the cytoplasm. It is induced by interferon and depends on the cell growth state. 2-Phosphodiesterase activity has two pH optima of hydrolysis of 2-5A, namely 7.1, and 7.9 and decreases after interferon treatment of cells. Thus, interferon treatment of cells leads to an increase of the 2-5A level in cell nuclei. One of the possible pathways for 2-5A action in cell nuclei is the regulation of (ADP-ribose)transferase activity. Treatment of L cells with 2-5A (A2pA2pA) leads to activation of ADP-ribosylation of proteins by a factor of 1.5 in a concentration range of 10(-9)-10(-7) M, but more higher concentrations of 2-5A inhibit this process up to 60%. Treatment of cells with actinomycin D has no influence on 2-5A induced changes in protein ADP-ribosylation. This result is indicative for a new pathway of interferon action and 2-5A mediated regulation of cell metabolism.
Mol Biol (Mosk)
PMID:[Metabolism of oligoadenylates in cell nuclei and regulation of protein ADP-ribosylation]. 377 90

Two human IgM lambda monoclonal antibodies (MAb) derived from the splenic lymphocytes of patients with idiopathic thrombocytopenia (Ben) and systemic lupus erythematosus (Wri) were studied. BEN-27 and WRI-170 hybridoma supernatants were screened for binding to ssDNA, dsDNA, poly (ADP-ribose), cardiolipin, histone subclasses and Klebsiella K30 cell wall antigen. Of this panel of antigens, BEN-27 and WRI-170 antibodies reacted only with histone H1. Their fine specificity was defined by direct and inhibition ELISA with synthetic peptides of the major human H1b variant. Antibody WRI-170 was shown to bind to both the N- and C-terminal peptides encompassing residues 1-16 and 204-218 of H1b whereas BEN-27 reacted only with peptide 204-218. To analyse the genetic origin of these autoantibodies, we determined the nucleotide sequence of the heavy (H) and light (L) chain variable regions of these two hybridomas. BEN-27 and WRI-170 MAbs were found to use VH1-DN1-JH4/V lambda 3-J lambda 2 and VH3-DIR2-D21/9-JH1/V lambda 2-J lambda 2 gene segment combinations respectively. Between 70 and 95% homology was demonstrated when the mRNA sequences for BEN-27 and WRI-170 were compared with published VH and V lambda germline sequences. This finding suggests that BEN-27 heavy and light chains and WRI-170 light chain use unidentified VH and V lambda germline gene segments whereas WRI-170 heavy chain derives from a VH gene segment recently identified. It is noteworthy that the CDRs of the two MAbs contain several negatively charged amino acids which are assumed to be of critical importance in antigen binding. Moreover, striking similarities are observed between BEN-27 heavy chain CDR2 and a previously described murine anti-H1 Ab heavy chain CDR2.
Mol Immunol 1994 Mar
PMID:Sequence analysis and fine specificity of two human monoclonal antibodies to histone H1. 751 Dec 11

Poly(ADP-ribosyl)ation is a posttranslational modification of nuclear proteins catalyzed by poly(ADP-ribose) polymerase (PARP; EC 2.4.2.30), with NAD+ serving as the substrate. PARP is strongly activated upon recognition of DNA strand breaks by its DNA-binding domain. Experiments with low-molecular-weight inhibitors of PARP have led to the view that PARP activity plays a role in DNA repair and possibly also in DNA replication, cell proliferation, and differentiation. Accumulating evidence for nonspecific inhibitor effects prompted us to develop a molecular genetic system to inhibit PARP in living cells, i.e., to overexpress selectively the DNA-binding domain of PARP as a dominant negative mutant. Here we report on a cell culture system which allows inducible, high-level expression of the DNA-binding domain. Induction of this domain leads to about 90% reduction of poly(ADP-ribose) accumulation after gamma-irradiation and sensitizes cells to the cytotoxic effect of gamma-irradiation and of N-methyl-N'-nitro-N-nitrosoguanidine. In contrast, induction does not affect normal cellular proliferation or the replication of a transfected polyomavirus replicon. Thus, trans-dominant inhibition of the poly(ADP-ribose) accumulation occurring after gamma-irradiation or N-methyl-N'-nitro-N-nitrosoguanidine is specifically associated with a disturbance of the cellular recovery from the inflicted damage.
Mol Cell Biol 1995 Jun
PMID:trans-dominant inhibition of poly(ADP-ribosyl)ation sensitizes cells against gamma-irradiation and N-methyl-N'-nitro-N-nitrosoguanidine but does not limit DNA replication of a polyomavirus replicon. 776 Aug 11

The coding sequence for human poly(ADP-ribose) polymerase was expressed inducibly in Saccharomyces cerevisiae from a low-copy-number plasmid vector. Cell free extracts of induced cells had poly(ADP-ribose) polymerase activity when assayed under standard conditions; activity could not be detected in noninduced cell extracts. Induced cells formed poly(ADP-ribose) in vivo, and levels of these polymers increased when cells were treated with the alkylating agent N-methyl-N'-nitro-N- nitrosoguanidine (MNNG). The cytotoxicity of this agent was increased in induced cells, and in vivo labelling with [3H]adenine further decreased their viability. Increased levels of poly(ADP-ribose) found in cells treated with the alkylating agent were not accompanied by lowering of the NAD concentration.
Mol Gen Genet 1994 Dec 15
PMID:Expression of human poly(ADP-ribose) polymerase in Saccharomyces cerevisiae. 783 Jul 16

ADP-ribosylation is a reversible post-translational modification of proteins involving the addition of the ADP-ribose moiety of NAD to an acceptor protein or amino acid. NAD:arginine ADP-ribosyltransferase, purified from numerous animal tissues, catalyzes the transfer of ADP-ribose to an arginine residue in proteins. The reverse reaction, catalyzed by ADP-ribosylarginine hydrolase, removes ADP-ribose, regenerating free arginine. An ADP-ribosylarginine hydrolase, purified extensively from turkey erythrocytes, was a 39-kDa monomeric protein under denaturing and non-denaturing conditions, and was activated by Mg2+ and dithiothreitol. The ADP-ribose moiety was critical for substrate recognition; the enzyme hydrolyzed ADP-ribosylarginine and (2-phospho-ADP-ribosyl)arginine but not phosphoribosylarginine or ribosylarginine. The hydrolase cDNA was cloned from rat and subsequently from mouse and human brain. The rat hydrolase gene contained a 1086-base pair open reading frame, with deduced amino acid sequences identical to those obtained by amino terminal sequencing of the protein or of HPLC-purified tryptic peptides. Deduced amino acid sequences from the mouse and human hydrolase cDNAs were 94% and 83% identical, respectively to the rat. Anti-rat brain hydrolase polyclonal antibodies reacted with turkey erythrocyte, mouse and bovine brain hydrolase. The rat hydrolase, expressed in E. coli, demonstrated enhanced activity in the presence of Mg2+ and thiol, whereas the recombinant human hydrolase was stimulated by Mg2+ but was thiol-independent. In the rat and mouse enzymes, there are five cysteines in identical positions; four of the cysteines are conserved in the human hydrolase.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Cell Biochem 1994 Sep
PMID:ADP-ribosylarginine hydrolases. 789 53

Several cases of ADP-ribosylation of endogenous proteins in procaryotes have been discovered and investigated. The most thoroughly studied example is the reversible ADP-ribosylation of the dinitrogenase reductase from the photosynthetic bacterium Rhodospirillum rubrum and related bacteria. A dinitrogenase reductase ADP-ribosyltransferase (DRAT) and a dinitrogenase reductase ADP-ribose glycohydrolase (DRAG) from R. rubrum have been isolated and characterized. The genes for these proteins have been isolated and sequences and show little similarity to the ADP-ribosylating toxins. Other targets for endogenous ADP-ribosylation by procaryotes include glutamine synthetase in R. rubrum and Rhizobium meliloti and undefined proteins in Streptomyces griseus and Pseudomonas maltophila.
Mol Cell Biochem 1994 Sep
PMID:Reversible ADP-ribosylation as a mechanism of enzyme regulation in procaryotes. 789 54

A cellular ADP-ribosyltransferase activity has been found in a variety of animals and tissues. The enzyme transfers ADP-ribose from NAD to elongation factor 2, inactivating the factor and thus inhibiting in vitro protein synthesis. Although, the mechanism of action of the cellular enzyme appears similar to diphtheria toxin and Pseudomonas exotoxin A, it differs from the toxins in that only a fraction of the EF-2 pool is modified. The endogenously ADP-ribosylated EF-2 has been detected by a variety of methods including two-dimensional electrophoresis and immunoprecipitation with elongation factor 2 antibody. The nature of the cellular ADP-ribosyltransferase and its physiological significance are unknown.
Mol Cell Biochem 1994 Sep
PMID:Cellular ADP-ribosylation of elongation factor 2. 789 55


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>