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)

ADP-ribosylation factors (ARFs) are approximately 20-kDa guanine nucleotide-binding proteins that stimulate the ADP-ribosyltransferase activity of cholera toxin in vitro. ARFs are highly conserved, ubiquitously expressed in eukaryotic cells and appear to be involved in vesicular protein transport. The two yeast ARFs are > 60% identical to mammalian ARFs and are essential for cell viability (Stearns, T., Kahn, R. A., Botstein, D., and Hoyt, M. A. (1990) Mol. Cell. Biol. 10, 6690-6699). Although the two yeast ARF proteins are 96% identical in amino acid sequence, the yeast ARF1 gene is constitutively expressed, whereas the ARF2 gene is repressed by glucose. Human ARF5 and ARF6 and a Giardia ARF differ substantially in size and amino acid identity from other mammalian and eukaryotic ARFs but will, as befits their designation, activate cholera toxin. Expression of human ARF5, ARF6, or Giardia ARF cDNA rescued the lethal yeast ARF double mutant (arf1, arf2). Strains rescued by human ARF5, ARF6, or Giardia ARF grew much more slowly than wild-type yeast or strains rescued with yeast ARF1. We infer from the impaired growth of these rescued strains that the homologous ARFs may have specific targeting information that does not interact effectively or efficiently with the yeast protein membrane trafficking system.
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PMID:Human and Giardia ADP-ribosylation factors (ARFs) complement ARF function in Saccharomyces cerevisiae. 144 92

Constitutive expression of human nuclear NAD+: protein ADP-ribosyltransferase (polymerizing) [pADPRT; poly(ADP-ribose)polymerase; EC 2.4.2.30] as an active enzyme in Saccharomyces cerevisiae, under the control of the alcohol dehydrogenase promoter, was only possible with simultaneous inhibition of ADP-ribosylation by 3-methoxybenzamide. Induction of fully active pADPRT from the inducible galactose epimerase promoter resulted in inhibition of cell division and morphological changes reminiscent of cell cycle mutants. Expression of a pADPRT cDNA truncated at its 5' end had no influence on cell proliferation at all. Obviously the amino-terminal part of the DNA binding domain containing the first "zinc finger", which is essential for inducibility of pADPRT activity by DNA breaks, is also required for inhibition of cell growth on expression in yeast. Full-length as well as truncated pADPRT molecules were directed to the cell nucleus where the fully active enzyme produced large amounts of poly(ADP-ribose) by automodification. Since pADPRT turned out to be the only target for ADP-ribosylation in these cells, elevated levels of poly(ADP-ribose) were the most likely cause of inhibition of cell division, presumably resulting from interaction with chromosomal proteins.
Mol Gen Genet 1992 Mar
PMID:Inhibition of cell proliferation in Saccharomyces cerevisiae by expression of human NAD+ ADP-ribosyltransferase requires the DNA binding domain ("zinc fingers"). 155 29

At least one of the procyclic acidic repetitive protein (PARP or procyclin) loci of Trypanosoma brucei is a small (5- to 6-kilobase) polycistronic transcription unit which is transcribed in an alpha-amanitin-resistant manner. Its single promoter, as mapped by run-on transcription analysis and UV inactivation of transcription, is located immediately upstream of the first alpha-PARP gene. Transcription termination occurs in a region approximately 3 kilobases downstream of the beta-PARP gene. The location of the promoter was confirmed by its ability to direct transcription of the bacterial chloramphenicol acetyltransferase gene in insect-form (procyclic) T. brucei. The putative PARP promoter is located in the region between the 3' splice acceptor site (nucleotide position 0) and nucleotide position -196 upstream of the alpha-PARP genes. Regulatory regions influencing the levels of PARP expression may be located further upstream. We conclude that a single promoter, which is located very close to the 3' splice acceptor site of the alpha-PARP genes, directs the transcription of a small, polycistronic, and alpha-amanitin-resistant transcription unit.
Mol Cell Biol 1990 Jul
PMID:Procyclic acidic repetitive protein (PARP) genes located in an unusually small alpha-amanitin-resistant transcription unit: PARP promoter activity assayed by transient DNA transfection of Trypanosoma brucei. 169 12

The genes for the variant surface glycoprotein (VSG) and procyclin are expressed in a mutually exclusive manner during the life cycle of Trypanosoma brucei and synthesize the most abundant mRNAs specific to the bloodstream and procyclic stages of the parasite, respectively. Genes belonging to the polycistronic transcription unit of the VSG gene (expression site-associated genes [ESAGs]) are uniquely expressed in the bloodstream form, but some members of ESAG families (genes related to ESAGs [GRESAGs]) are independently transcribed outside the VSG gene expression site. We report here that a gene related to ESAG 2, GRESAG 2.1, is present and expressed in a procyclin gene transcription unit (PARP A locus), which is polycistronic. Members of the ESAG 2 family are thus present in the two major differentially stage-regulated transcription units of this parasite.
Mol Cell Biol 1991 Mar
PMID:A similar gene is shared by both the variant surface glycoprotein and procyclin gene transcription units of Trypanosoma brucei. 199 4

Pertussis toxin (PT) is a major virulence factor of Bordetella pertussis, and also an important protective antigen. PT is an oligomeric A-B type toxin in which the S1 subunit has the ADP-ribosyltransferase activity whereas the B-oligomer mediates its binding to target cell receptors. To analyze the immunological properties of S1 and to generate probes to localize and characterize S1 functional domains, we synthesized four sets of peptides and peptide analogs corresponding to potentially critical regions of the S1 subunit. Two peptide-KLH conjugates were found to be capable of inducing PT-neutralizing antibodies in rabbits as judged by the CHO cell clustering assay. These peptides comprise residues 1-18 (N18-S1) and 121-138 (NAD-S1), respectively. Immunization with the unconjugated C-terminal peptide C35-S1 (residues 201-235) in the presence of Freund's adjuvant also elicited PT-neutralizing antibodies, indicating that the C-terminal region of S1 contains a potent functional T-helper cell epitope. Using truncated peptide analogs of N18-S1, we have demonstrated that the first three N-terminal residues are essential for inducing neutralizing antibodies. The NAD-S1 peptide elicited a neutralizing antibody response when coupled to KLH via its N-terminal end but not via its C-terminal residue. Identification of these B-cell neutralization epitopes represents a first step towards the rational design of a synthetic vaccine against whooping cough.
Mol Immunol 1991 Mar
PMID:Structural and functional analysis of the S1 subunit of pertussis toxin using synthetic peptides. 201 95

We have previously shown that there are multiple GTP-binding proteins (G proteins) with Mr values of about 20,000 in bovine brain membranes and identified one G protein with a Mr of 20,000 as the rho gene product. We have also shown that this rho gene product is ADP-ribosylated by an ADP-ribosyltransferase contaminated in botulinum toxin type C1. In the present studies, we have purified another G protein with a Mr of about 21,000 to near homogeneity from bovine brain membranes by several column chromatographies and identified it as the rhoA gene product. Further analysis of the amino acid sequence of the G protein, which we have purified and identified as the rho gene product previously, has revealed that this G protein is the rhoB gene product. The rhoA gene product binds maximally about 0.9 mol of [35S]guanosine 5'-(3-O-thio) triphosphate (GTP gamma S)/mol of protein with a K d value of about 20 nM. [35S]GTP gamma S-binding to the rhoA gene product is inhibited by pretreatment with N-ethylmaleimide. The rhoA gene product hydrolyzes GTP to liberate Pi with a turnover number of about 0.01 min-1. Moreover, the rhoA gene product is ADP-ribosylated by an ADP-ribosyltransferase contaminated in botulinum toxin type Cl. About 0.3 mol of ADP-ribose is maximally incorporated into 1 mol of the rhoA gene product. The ADP ribosylation of the rhoA gene product does not affect its GTP gamma S-binding or GTPase activity. These properties of the rhoA gene product are similar those of the rhoB gene product described previously. These results together with the earlier observations indicate that there are at least two rho gene products (rhoA, B) among three members of the rho gene family (rhoA, B, C) in bovine brain membranes and that both of them are ADP-ribosylated by an ADP-ribosyltransferase contaminated in botulinum toxin type C1.
Brain Res Mol Brain Res 1990 Jan
PMID:Purification and characterization from bovine brain membranes of a GTP-binding protein with a Mr of 21,000, ADP-ribosylated by an ADP-ribosyltransferase contaminated in botulinum toxin type C1--identification as the rhoA gene product. 215 99

The A subunit of cholera toxin contains the ADP-ribosyltransferase activity in its major constituent polypeptide A1 (Mr 23,000) which is responsible for the elevation of cAMP typically observed with most mammalian cell types after exposure to the toxin. The primary structure of the A subunit, recently established by sequence analyses, is presented and used as the basis for the secondary structure prediction according to the method of Chou and Fasman. The results indicated the presence of 27% alpha-helix, 25% beta-structure, 12% beta-turn, and 36% random coil. The majority of the beta-structure consisted of six strands located in the NH2-terminal portion of the molecule (residues 33-106) covering one-half of the region corresponding to the A1 polypeptide portion. The beta-sheet domain led immediately into the active site region characterized by the alternating structures of beta-pleated sheet and alpha-helix (residues 95-140) similar to that reported for other NAD+ binding proteins. The presence of this structural feature in the region was confirmed by the use of another predictive method (J. Garnier et al., J. Mol. Biol. 1978, 120, 97-120). In addition, two regions (residues 14-18 and 200-214), previously identified to contain binding sites for the B subunit as evidenced by chemical modification and monoclonal antibody studies, were found to be in alpha-helix configuration.
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PMID:Cholera toxin A subunit: functional sites correlated with regions of secondary structure. 240 74

Signal-transducing GTP-binding Proteins of Mammalian Heart and Lungs. Journal of Molecular and Cellular Cardiology (1989) 21 (Suppl I) 91-95. Three distinct G-proteins have been found in mammalian heart sarcolemma: Gi (alpha i = 40 kDa, beta = 36 kDa, and lambda less than 14 kDa), Gp (alpha p = 23 kDa, beta = 36 kDa, and lambda less than 14 kDa), and Gs (alpha s = 42 kDa). ADP-ribosylation of sarcolemmal alpha i by pertussis toxin (PT) or preincubation of sarcolemma with protein kinase C and PMA resulted in increased adenylate cyclase activity and blockade of GTP-dependent inhibition by carbachol whereas the GTP-dependent activating effect of isoproterenol on the adenylate cyclase was preserved. ADP-ribosylation of alpha i in sarcolemma by endogenous NADP-sensitive ADP-ribosyltransferase abolished the PT-induced ADP-ribosylation of alpha i. Gpp (NH)p attenuated the PT-induced ADP-ribosylation of alpha i and promoted the cholera toxin (CT)-induced ADP-ribosylation of alpha s. The CT-induced alpha s ADP-ribosylation was enhanced in the presence of heart cytosol. Soluble Gi- and Gs-proteins were identified in lung cytosol. The 40 kDa alpha i in membrane and soluble fractions was ADP-ribosylated by PT, while the soluble 42 kDa alpha s was ADP-ribosylated by CT in lung tissue. The ADP-ribosylation of soluble alpha i by PT-suppressed guanyl nucleotide binding to Gi. The apparent molecular mass of partially purified soluble Gi was 75 kDa.
J Mol Cell Cardiol 1989 Feb
PMID:Signal-transducing GTP-binding proteins of mammalian heart and lungs. 249 81

Guanine nucleotide-binding (G) proteins are involved in several transmembrane signaling systems. Choleragen (cholera toxin) activates adenylate cyclase by catalyzing the ADP-ribosylation of Gs alpha, the stimulatory G protein of the cyclase system. This reaction is enhanced by another guanine nucleotide-binding protein termed ADP-ribosylation factor or ARF that was purified from bovine brain membranes [R. A. Kahn and A. G. Gilman, Journal of Biological Chemistry (1986) 261, 7906-7911]. It was recently found that this ARF also increases the NAD:agmatine and NAD:protein ADP-ribosyltransferase, NAD glycohydrolase and auto-ADP-ribosylation activities of the toxin. We have purified and characterized two soluble proteins from bovine brain that act in a similar fashion to enhance choleragen activity in each of these reactions. The membrane and soluble factors are all proteins of approximately 19 kDa that require GTP or GTP analogues for activity and are ADP-ribosylated by the toxin. The ARF proteins apparently interact directly with choleragen in a GTP-dependent fashion to increase its catalytic activity and thus are part of a G protein cascade through which the toxin activates adenylate cyclase. The physiological function of the ARF proteins, as well as their possible relationships to the ras oncogene products and/or the family of G proteins that includes Gs alpha, remains to be determined.
J Mol Cell Cardiol 1989 Feb
PMID:Participation of a guanine nucleotide-binding protein cascade in cholera toxin activation of adenylate cyclase. 249 82

Nitrogen fixation activity in the photosynthetic bacterium Rhodospirillum rubrum is controlled by the reversible ADP-ribosylation of the dinitrogenase reductase component of the nitrogenase enzyme complex. This report describes the cloning and characterization of the genes encoding the ADP-ribosyltransferase (draT) and the ADP-ribosylglycohydrolase (draG) involved in this regulation. These genes are shown to be contiguous on the R. rubrum chromosome and highly linked to the nifHDK genes. Sequence analysis revealed the use of TTG as the initiation codon of the draT gene as well as a potential open reading frame immediately downstream of draG. The mono-ADP-ribosylation system in R. rubrum is the first in which both the target protein and modifying enzymes as well as their structural genes have been isolated, making it the model system of choice for analysis of this post-translational regulatory mechanism.
Mol Gen Genet 1989 Aug
PMID:Genes coding for the reversible ADP-ribosylation system of dinitrogenase reductase from Rhodospirillum rubrum. 250 27


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