Disease relevance of Art1

• We have identified and cloned a GPI-linked ADP-ribosyltransferase from Yac-1 mouse T-cell lymphoma cells [1].
• The Yac-1 and Yac-2 enzymes, expressed as glutathione S-transferase fusion proteins in Escherichia coli, were used to compare their ADP-ribosyltransferase and NAD glycohydrolase activities [2].
• ADP-ribosyltransferase activity of pertussis toxin and immunomodulation by Bordetella pertussis [3].
• Cytotoxic T-cells (CTL) could not be detected in spleen cell suspensions from Moloney murine sarcoma virus (M-MuSV)-induced tumor-bearing A/Sn and (A/Sn X C57BL/6) F1 mice, with the A/Sn-derived natural killer (NK)-sensitive YAC-1 lymphoma cells used as targets [4].
• The mutant CT was made by substitution of serine with phenylalanine at position 61 of the A subunit (S61F), which resulted in loss of ADP ribosyltransferase activity and toxicity [5].

Psychiatry related information on Art1

• Treatment with r-interferon gamma or rIL-2 on days 1 through 3 after C1300-NRB inoculation significantly prolonged the mean tumor latency period, decreased the tumor growth rate, and enhanced in vitro NK killing of C1300-NRB and YAC-1 [6].

High impact information on Art1

• These data suggest that the ADP-ribosyltransferase activity is necessary for both pathogenicity and optimum immunoprotection [3].
• The NK cells generated by this protocol lysed the NK-sensitive target YAC-1 and expressed markers of mature NK cells with the notable absence of Ly-49 major histocompatibility complex (MHC) receptors [7].
• The inhibitory effect of the toxin is dependent on its G protein-modifying ADP-ribosyltransferase activity and can be reversed by phorbol myristic acetate, which bypasses cell surface receptors to trigger activation-dependent adhesion [8].
• Fragmentin activity was not dependent on protein synthesis, as cycloheximide treatment of YAC-1 cells did not prevent DNA damage [9].
• In addition to conventional cellular targets such as the YAC-1 and MBL-2 lymphomas, this cloned line also lysed lipopolysaccharide-activated B lymphocytes [10].

Chemical compound and disease context of Art1

• Effects of dimethyl sulfoxide treatment on H-2 expression and susceptibility to NK- or cytotoxic T-lymphocyte-mediated lysis of the YAC-1 lymphoma and its beta 2-microglobulin-deficient variant [11].
• The effects of dimethyl sulfoxide (DMSO) on H-2 expression and susceptibility to NK- and cytotoxic T-lymphocyte (CTL)-mediated lysis in the murine T-cell lymphoma YAC-1 and its beta-2-microglobulin (beta 2m)-deficient variant were studied [11].
• The natural killer activity against the YAC-1 (a T-cell lymphoma) cell line in spleen cells of the nude mice challenged with human xenogeneic tumor (KK cell line) was not affected by treatment with cimetidine while inhibiting the tumor growth [12].
• In the present study, we examined the action of rho p21, its inhibitory GDP/GTP exchange protein (named rho GDI), its stimulatory GDP/GTP exchange protein (named smg GDS), and Clostridium botulinum ADP-ribosyltransferase C3, known to selectively ADP-ribosylate rho p21 and to impair its function, in cell motility (chemokinesis) of Swiss 3T3 cells [13].
• With chronic indomethacin therapy alone, NK-like (AGM-1+, Thy-1-,Lyt-2-) killer lymphocytes (capable of killing NK sensitive YAC-1 lymphoma and B16F10 melanoma targets) appeared in the spleen, but not lungs; no killer activity was generated in macrophages at either site [14].

Biological context of Art1

• The deduced amino acid sequence of Art1 exhibits the characteristic features of a glycosylphosphatidylinositol-anchored membrane protein [15].
• The Art1 gene encompasses four exons spanning 20 kb of genomic DNA [15].
• The availability of the Art1 gene provides the basis for applying transgene and knockout technologies to further probe the function of this gene product [15].
• While human ART1 is not represented in the public expressed sequence tag (EST) database, the database contains 14 mouse Art1 ESTs [15].
• Rapid induction of naive T cell apoptosis by ecto-nicotinamide adenine dinucleotide: requirement for mono(ADP-ribosyl)transferase 2 and a downstream effector [16].

Anatomical context of Art1

• Northern blot and reverse transcription-PCR analyses demonstrate prominent expression of Art1 in cardiac and skeletal muscle, and lower levels in spleen, lung, liver and fetal tissues [15].
• Several proteins with NAD+:arginine ADP-ribosyltransferase (ART) activity are expressed in T cells and affect their function [17].
• Molecular characterization of a glycosylphosphatidylinositol-linked ADP-ribosyltransferase from lymphocytes [1].
• Molecular cloning and characterization of a mono(ADP-ribosyl)transferase from human testis [18].
• ADP-ribosyltransferase-specific modification of human neutrophil peptide-1 [19].

Associations of Art1 with chemical compounds

• We have characterized the gene for mouse arginine-specific ADP-ribosyltransferase, Art1 [15].
• Using agmatine as the ADP-ribose acceptor, the Yac-1 enzyme was predominantly an ADP-ribosyltransferase, whereas the transferase and NAD glycohydrolase activities of the recombinant Yac-2 protein were equivalent [2].
• This messenger encodes for a precursor protein of 367 aa (MW: 41.5 kDa) which exhibits a peptide signal, consensus domains for mono(ADP-ribosyl)transferase and a C terminal part which contains three repeated motives (GEKNQKLEDH) and a region characteristic of glycophosphatidyl inositol anchored proteins [18].
• Fluorescence-activated cell sorter analysis revealed induction of H-2Kk and beta 2m 3 days after culture of YAC-1 with DMSO, whereas optimal H-2Dd induction required more than 1 week [11].
• Urethan (1 mg/g) inoculated into 6- to 8-week-old A/J mice produced considerable depression of cytotoxic activity of spleen cells against YAC-1 or RL male 1 tumor cells [20].

Physical interactions of Art1

• A "hybrid gene" (MTKb) comprised of the human metallothionein IIA promoter ligated to the genomic sequence of the major histocompatibility complex class I (H-2Kb) gene was subcloned into the expression vector pSV2neo and transfected into the natural killer (NK) cell-sensitive YAC-1 lymphoma [21].
• Antibodies to this epitope blocked the ADP-ribosyltransferase activity of ETA and appeared to interfere with binding of the substrate elongation factor 2 to the enzymatic active site of the ETA molecule [22].

Regulatory relationships of Art1

• YAC-1 and Jurkat expressed Fas and were susceptible to anti-Fas MAb or rhuman Fas ligand (rhFasL)-induced lysis [23].
• In contrast to the above three MAbs, MAb Ex-2A10 (IgG2b) greatly inhibited ADP-ribosyltransferase but showed no inhibition of Ex-A incorporation and no neutralizing activity against cell toxicity [24].
• The ADP-ribosyltransferase activity of the toxin was expressed through incubation with dithiothreitol and erythrocyte membranes [25].
• The tumor-infiltrating NK cells from 3LL-inoculated mice produced a high level of interferon-gamma by co-culture with 3LL and showed enhanced cytotoxic activities against both NK-sensitive (YAC-1) and NK-resistant (3LL and P815) tumors [26].
• The mixture of DCI and BLT esterase active NK cell lysate triggered DNA fragmentation in isolated YAC-1 nuclei [27].

Other interactions of Art1

• Mouse Rt6.1 is a thiol-dependent arginine-specific ADP-ribosyltransferase [28].
• ART2.2 is a GPI-anchored ecto-ADP-ribosyltransferase (ART) related to ADP-ribosylating bacterial toxins [29].
• Although the cells contained dense granules reactive to mAb against perforin, they exerted no conventional cytolytic activity against YAC-1 [30].
• Spleen cells from naive HSK-susceptible CAL-20 (Igh-1d) and BALB/c (Igh-1a) mice lysed YAC-1 targets better than HSK-resistant C.B-17 (Igh-1b) mice [31].
• Thus, we examined the effect that dimethyl 2,2-dichlorovinyl phosphate (DDVP), an organophosphorus pesticide has on NK, CTL and LAK activities of PKO mice in vitro using the Fas antigen-positive YAC-1 cell as a target in the present study [32].

Analytical, diagnostic and therapeutic context of Art1

• Southern blot analyses indicate that Art1 is a single-copy gene [15].
• Molecular cloning of a functional murine arginine-specific mono-ADP-ribosyltransferase and its expression in lymphoid cells [33].
• Natural killer (NK) cells (poly I:C induced, x-ray resistant, nonadherent, Thy-1-, Ly-1.1-, Ly-2.1-, anti-asialo GM1-positive, and cytotoxic for YAC-1) suppressed T lymphocyte proliferation in mixed lymphocyte reaction (MLR) and autologous MLR cultures [34].
• In addition, the YAC-R clones, like the parental YAC-1 cell line, were able to stimulate the release of NKCF during co-culture with spleen cells [35].
• Cells were fractionated by centrifugation on discontinuous Percoll density gradients, and each fraction was tested for NK activity against YAC-1 targets and for the presence of LGL [36].

References