Disease relevance of ART1

• ADP-ribosylated HNP-1 was identified in bronchoalveolar lavage fluid (BALF) from patients with asthma, idiopathic pulmonary fibrosis, or a history of smoking (and having two common polymorphic forms of ART1 that differ in activity), but not in normal volunteers or patients with lymphangioleiomyomatosis [1].
• Screening of primary cells and established cell lines by FACS revealed expression of ART1 by monocytes, neutrophils and myeloid leukemia cell lines but not by cell lines derived from solid tumors [2].
• Further characterisation has identified a putative novel gene (ART1) that is up-regulated specifically in pancreatic cancer as well as another sequence with similarity to genes involved in differentiation (POU domains) [3].
• The carboxyl half of the protein, synthesized as a fusion protein in E. coli, possessed NADase, but not ADP-ribosyltransferase activity [4].
• Dissection of thymocyte signaling pathways by in vivo expression of pertussis toxin ADP-ribosyltransferase [5].

Psychiatry related information on ART1

• The main conclusion is that the ART-2 neural network is promising as a decision-making aid [6].

High impact information on ART1

• Botulinum C2 toxin is another toxin which has been reported to possess ADP-ribosyltransferase activity [7].
• In the complex, the ADP-ribosyltransferase activity of C3 is blocked, while binding of NAD and NAD-glycohydrolase activity remain [8].
• Using the translocation of C-domain ADP-ribosyltransferase activity across the endosomal membrane as an assay, the CTF complex activity was 650-800-fold purified from human T cell and yeast extracts, respectively [9].
• Ribosylation of Val14rho with the ADP-ribosyltransferase C3 from clostridium botulinum, before microinjection, renders the protein biologically inactive, but it has no effect on either its intrinsic biochemical properties or on its interaction with the GTPase activating protein, rho GAP [10].
• Additionally, a decreased activity of NAD: protein ADP-ribosyltransferase was found for three FA cell lines [11].

Chemical compound and disease context of ART1

• Alkylation of cysteine 41, but not cysteine 200, decreases the ADP-ribosyltransferase activity of the S1 subunit of pertussis toxin [12].
• Characterization of the catalytic site of the ADP-ribosyltransferase Clostridium botulinum C2 toxin by site-directed mutagenesis [13].
• The linkage of ADP-ribose-Gi alpha in the membranes formed by ADP-ribosyltransferase C was as stable to hydroxylamine as that formed by pertussis toxin [14].
• Structure predictions of SpvB indicated that it is composed of a C-terminal ADP-ribosyltransferase domain fused via a poly proline stretch to a N-domain resembling the N-domain of the secretory toxin TcaC from nematode-infecting enterobacteria [15].
• Cholera and pertussis toxins each contain a subunit with ADP-ribosyltransferase activity, sharing a region of nearly identical amino acid sequence near the NH2 terminus [16].

Biological context of ART1

• The deduced amino acid sequence of ART5 shows 87% sequence identity to its orthologue from the human, and 37 and 32% identity to its murine paralogues ART1 and ART2 [17].
• ART2-which has sparked interest because of its ability to activate the cytolytic P2X7 purinergic receptor by ADP-ribosylation-is encoded by two functional gene copies in the mouse genome while the human genome carries two inactivated ART2 pseudogenes [2].
• 5. In conclusion, we propose that PDGF-BB-dependent signalling may be regulated by post-translational modification of the growth factor by ART1 at the cell surface [18].
• Five paralogs (ART1-5) have been cloned but only four of them are expressed in human due to a defective ART2 gene, and six in the mouse as the result of ART2 gene duplication [19].
• Analysis of mono-ADP-ribosyltransferase 4 gene expression in human monocytes: splicing pattern and potential regulatory elements [20].

Anatomical context of ART1

• We reported that ART1, a mammalian ADP-ribosyltransferase, present in epithelial cells lining the human airway, modified HNP-1, altering its function [1].
• When measuring expression of the mRNA of ART1, 3, 4 and 5, only ART3 mRNA was detected in unstimulated monocytes [21].
• ADP-ribosyltransferase-specific modification of human neutrophil peptide-1 [1].
• In skeletal muscle and lymphocytes, ART1 modifies specific members of the integrin family of adhesion molecules, suggesting that ADP-ribosylation affects cell-matrix or cell-cell interactions [22].
• Fibroblasts expressing human ART1 at the cell surface showed reduced mitogenic responses to PDGF-BB, but not to PDGF-AA [18].

Associations of ART1 with chemical compounds

• 1. Arginine-specific ADP-ribosyltransferase (ART1) is expressed on the surface of a number of cell types, and catalyses the transfer of ADP-ribose from NAD(+) to target proteins [18].
• This loss of mitogenic response in cells expressing ART1 activity was reversed by the addition of agmatine (an ART1 substrate) [18].
• The results revealed no differences in the capacity of phosphoinositide-specific phospholipase C to cleave the two ART1 isoforms from the plasma membrane [23].
• RT6 proteins are glycosylphosphatidylinositol (GPI)-linked alloantigens that are localized to cytotoxic T lymphocytes and that have nicotinamide adenine dinucleotide glycohydrolase and adenosine diphosphate (ADP)-ribosyltransferase activities [24].
• An increase in ADP-ribosyltransferase activity was observed when cells were treated for 16 h with bacterial lipopolysaccharide (LPS) [21].

Regulatory relationships of ART1

• ADP-ribosylation factor 4 (ARF4) is a member of a family of approximately 20 kDa guanine nucleotide-binding proteins that were initially identified by their ability to stimulate the ADP-ribosyltransferase activity of cholera toxin in vitro [25].
• The ADP-ribosyltransferase activity of ExoT stimulated depolymerization of the actin cytoskeleton independent of Rho GTPase-activating protein function, and ExoT was subsequently shown to ADP-ribosylate Crk (CT10 regulator of kinase)-I and Crk-II [26].
• Other protein synthesis inhibitory proteins act by their ADP-ribosyltransferase activity which modify and thus inactivate elongation factor-2 [27].

Other interactions of ART1

• We conclude that ADP-ribosylation of HNP-1 appears to be primarily an activity of ART1 and occurs in inflammatory conditions and disease [1].
• Similar responses were observed after exposure of the cells to platelet-activating factor or interleukin-8, and we conclude that some of the effects of these chemotaxins are mediated by translocation of an intracellular pool of ART1 to its site of catalytic activity on the outer aspect of the plasma membrane [28].
• A combination of different technological approaches reveals that ecto-ARTs are expressed in different tissues with privileged sites such as heart and skeletal muscles for ART1, T lymphocytes for ART2 or testis for ART5 [19].
• Using in situ hybridization with specific ART3 and ART4 oligonucleotides, we also identified two additional members of the RT6 superfamily in epithelial cells [24].
• However, in stratified analysis, the OGG1 S326C variant genotypes in ever smokers (odds ratio, 0.74; 95% confidence interval, 0.56-0.99) and ADP-ribosyltransferase (ADPRT) V762A variant genotypes in never smokers (odds ratio, 0.58; 95% confidence interval, 0.37-0.91) conferred a significantly reduced risk [29].

Analytical, diagnostic and therapeutic context of ART1

• Using in situ analysis and Northern blot analysis, we identified ART1 messenger RNA (mRNA) in airway epithelial cells [24].
• Following removal of GST immunoreactivity by immunoprecipitation, these antibodies were used to measure the abundance of immunoreactive ART1 on the surface of PMNs [28].
• 3. A rat ART1 transcript was amplified by rtPCR from rat skeletal muscle, and was noted to share 94% homology with the mouse ART1 cDNA sequence [30].
• Sequence analyses reveal that the Art5 gene encompasses six exons spanning 8 kb of genomic DNA [17].
• When PT was incubated with ATP prior to Bio-Gel P-100 gel filtration, approximately 8% of the S1 subunit dissociated from the B oligomer, as determined by ADP-ribosyltransferase assays of the column eluant [31].

References