Characterization of Glycosylphosphatidylinositiol-Anchored, Secreted, and Intracellular Vertebrate Mono-Adp-Ribosyltransferases

Okazaki, Ian J.; Moss, Joel

doi:10.1146/annurev.nutr.19.1.485

Cited by 71 publications

(58 citation statements)

References 110 publications

(108 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Because low-potency PARP inhibitors are less potent, higher concentrations are necessary to inhibit PARP activity, increasing the likelihood that other ␤-NAD ϩ binding proteins are nonselectively affected. High concentrations of low-potency PARP inhibitors inhibit other ␤-NAD ϩ binding proteins, including mono(ADP ribose) transferases and NADases (42). Nicotinamide can increase gene expression by interfering with the ␤-NAD ϩ binding site of Sir2 (silent information regulatory 2) family of histone/protein deacetylases (43) or the transcriptional corepressor CtBP (COOH-terminal binding protein) (44).…”

Section: Discussionmentioning

confidence: 99%

MafA Expression and Insulin Promoter Activity Are Induced by Nicotinamide and Related Compounds in INS-1 Pancreatic β-Cells

Tai

Linning

et al. 2006

Diabetes

View full text Add to dashboard Cite

Nicotinamide has been reported to induce differentiation of precursor/stem cells toward a ␤-cell phenotype, increase islet regeneration, and enhance insulin biosynthesis. Exposure of INS-1 ␤-cells to elevated glucose leads to reduced insulin gene transcription, and this is associated with diminished binding of pancreatic duodenal homeobox factor 1 (PDX-1) and mammalian homologue of avian MafA/LMaf (MafA). Nicotinamide and other low-potency poly(ADP-ribose) polymerase (PARP) inhibitors were thus tested for their ability to restore insulin promoter activity. The low-potency PARP inhibitors nicotinamide, 3-aminobenzamide, or PD128763 increased expression of a human insulin reporter gene suppressed by elevated glucose. In contrast, the potent PARP-1 inhibitors PJ34 or INO-1001 had no effect on promoter activity. Antioxidants, including N-acetylcysteine, lipoic acid, or quercetin, only minimally induced the insulin promoter. Site-directed mutations of the human insulin promoter mapped the low-potency PARP inhibitor response to the C1 element, which serves as a MafA binding site. INS-1 cells exposed to elevated glucose had markedly reduced MafA protein and mRNA levels. Low-potency PARP inhibitors restored MafA mRNA and protein levels, but they had no affect on PDX-1 protein levels or binding activity. Increased MafA expression by low-potency PARP inhibitors was independent of increased MafA protein or mRNA stability. These data suggest that low-potency PARP inhibitors increase insulin biosynthesis, in part, through a mechanism involving increased MafA gene transcription. Diabetes 55: [742][743][744][745][746][747][748][749][750] 2006 A cute elevations in glucose concentration regulate pancreatic ␤-cell function, including stimulation of insulin secretion and biosynthesis. In contrast, chronic exposure of ␤-cells to elevated glucose diminishes cell function by altering ␤-cell gene expression (1) through a poorly understood process termed glucose toxicity. One of the associated outcomes of glucose toxicity on ␤-cells is a reduction in insulin gene expression (1-6) that results from decreased insulin promoter activity (2-4,7-9). The decline in insulin promoter activity correlates to a reduction in expression and/or binding of ␤-cell-enriched transcription factors, including pancreatic duodenal homeobox factor 1 (PDX-1) (1,4 -6,8,10) and mammalian homologue of avian MafA/L-Maf (MafA; also known as RIPE3b1 or C1 activator) (3,4,7, 9,11). The biochemical mechanisms whereby elevated glucose reduced PDX-1 and MafA binding activity are unknown; however, a number of studies support the possible involvement of oxidative stress (6,(11)(12)(13)(14).Nicotinamide has historically been used to augment pancreatic ␤-cell differentiation and protect islet cells from toxic insults. Treatment of cultured fetal human or porcine islet-like cell clusters, pancreatic precursor/stem cells, or embryonic stem cells with nicotinamide enhances the differentiation of ␤-cells, and this is characterized by increased insulin mRNA levels, biosynthes...

show abstract

Section: Discussionmentioning

confidence: 99%

MafA Expression and Insulin Promoter Activity Are Induced by Nicotinamide and Related Compounds in INS-1 Pancreatic β-Cells

Tai

Linning

et al. 2006

Diabetes

View full text Add to dashboard Cite

show abstract

“…MARTs and MARHs are opposing arms of an ADP-ribosylation cycle (306,374). In contrast to the case for the prokaryotic ADP-ribosylation cycle, the functional relationship between MARTs and MARHs in eukaryotes is poorly documented (304,305). Thus, the detailed mechanisms of coupling of MARTs and MARHs in eukaryotic mono-ADPribosylation cycles need to be investigated further.…”

Section: Mono-adp-ribosyltransfer Reactionsmentioning

confidence: 99%

Nuclear ADP-Ribosylation Reactions in Mammalian Cells: Where Are We Today and Where Are We Going?

Hassa

Haenni

Elser

et al. 2006

Microbiol Mol Biol Rev

635

644

View full text Add to dashboard Cite

SUMMARY Since poly-ADP ribose was discovered over 40 years ago, there has been significant progress in research into the biology of mono- and poly-ADP-ribosylation reactions. During the last decade, it became clear that ADP-ribosylation reactions play important roles in a wide range of physiological and pathophysiological processes, including inter- and intracellular signaling, transcriptional regulation, DNA repair pathways and maintenance of genomic stability, telomere dynamics, cell differentiation and proliferation, and necrosis and apoptosis. ADP-ribosylation reactions are phylogenetically ancient and can be classified into four major groups: mono-ADP-ribosylation, poly-ADP-ribosylation, ADP-ribose cyclization, and formation of O-acetyl-ADP-ribose. In the human genome, more than 30 different genes coding for enzymes associated with distinct ADP-ribosylation activities have been identified. This review highlights the recent advances in the rapidly growing field of nuclear mono-ADP-ribosylation and poly-ADP-ribosylation reactions and the distinct ADP-ribosylating enzyme families involved in these processes, including the proposed family of novel poly-ADP-ribose polymerase-like mono-ADP-ribose transferases and the potential mono-ADP-ribosylation activities of the sirtuin family of NAD+-dependent histone deacetylases. A special focus is placed on the known roles of distinct mono- and poly-ADP-ribosylation reactions in physiological processes, such as mitosis, cellular differentiation and proliferation, telomere dynamics, and aging, as well as “programmed necrosis” (i.e., high-mobility-group protein B1 release) and apoptosis (i.e., apoptosis-inducing factor shuttling). The proposed molecular mechanisms involved in these processes, such as signaling, chromatin modification (i.e., “histone code”), and remodeling of chromatin structure (i.e., DNA damage response, transcriptional regulation, and insulator function), are described. A potential cross talk between nuclear ADP-ribosylation processes and other NAD+-dependent pathways is discussed.

show abstract

“…To investigate this we first compared the structures of PARP and ART2. Primary sequence analysis revealed three regions of similarity in the catalytic cores of mARTs and a typical PARP (PARP1, PDB 1A26) (31). Backbone structural alignment of PARP and ART2 (ART2.2, PDB 1GXZ) also demonstrated three regions of structural similarity (Fig.…”

Section: Conservation Of Structural Elements and Catalyticmentioning

confidence: 92%

ART2, a T Cell Surface Mono-ADP-ribosyltransferase, Generates Extracellular Poly(ADP-ribose)

Morrison

Moss

Stevens

et al. 2006

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

NAD functions in multiple aspects of cellular metabolism and signaling through enzymes that covalently transfer ADP-ribose from NAD to acceptor proteins, thereby altering their function. NAD is a substrate for two enzyme families, mono-ADP-ribosyltransferases (mARTs) and poly(ADP-ribose) polymerases (PARPs), that covalently transfer an ADP-ribose monomer or polymer, respectively, to acceptor proteins. ART2, a mART, is a phenotypic marker of immunoregulatory cells found on the surface of T lymphocytes, including intestinal intraepithelial lymphocytes (IELs). We have shown that the auto-ADP-ribosylation of the ART2.2 allelic protein is multimeric. Our backbone structural alignment of ART2 (two alleles of the rat art2 gene have been reported, for simplicity, the ART2.2 protein investigated in this study will be referred to as ART2) and PARP suggested that multimeric auto-ADP-ribosylation of ART2 may represent an ADP-ribose polymer, rather than multiple sites of mono-ADPribosylation. To investigate this, we used highly purified recombinant ART2 and demonstrated that ART2 catalyzes the formation of an ADP-ribose polymer by sequencing gel and by HPLC and MS/MS mass spectrometry identification of PR-AMP, a breakdown product specific to poly(ADP-ribose). Furthermore, we identified the site of ADP-ribose polymer attachment on ART2 as Arg-185, an arginine in a crucial loop of its catalytic core. We found that endogenous ART2 on IELs undergoes multimeric auto-ADP-ribosylation more efficiently than ART2 on peripheral T cells, suggesting that these distinct lymphocyte populations differ in their ART2 surface topology. Furthermore, ART2.2 IELs are more resistant to NAD-induced cell death than ART2.1 IELs that do not have multimeric auto-ADP-ribosylation activity. The data suggest that capability of polymerizing ADP-ribose may not be unique to PARPs and that poly(ADP-ribosylation), an established nuclear activity, may occur extracellularly and modulate cell function.

show abstract

Characterization of Glycosylphosphatidylinositiol-Anchored, Secreted, and Intracellular Vertebrate Mono-Adp-Ribosyltransferases

Cited by 71 publications

References 110 publications

MafA Expression and Insulin Promoter Activity Are Induced by Nicotinamide and Related Compounds in INS-1 Pancreatic β-Cells

MafA Expression and Insulin Promoter Activity Are Induced by Nicotinamide and Related Compounds in INS-1 Pancreatic β-Cells

Nuclear ADP-Ribosylation Reactions in Mammalian Cells: Where Are We Today and Where Are We Going?

ART2, a T Cell Surface Mono-ADP-ribosyltransferase, Generates Extracellular Poly(ADP-ribose)

Contact Info

Product

Resources

About