Ubiquitin Modification by the E3 Ligase/ADP-Ribosyltransferase Dtx3L/Parp9

Yang, Chunsong; Jividen, Kasey; Spencer, A. Benjamin; Dworak, Natalia M; Li, Ni; Oostdyk, Luke T.; Chatterjee, Mandovi; Kuśmider, Beata; Reon, Brian J.; Parlak, Mahmut; Gorbunova, Vera; Abbas, Tarek; Jeffery, Erin; Sherman, Nicholas E.; Paschal, Bryce M.

doi:10.1016/j.molcel.2017.04.028

Cited by 178 publications

(236 citation statements)

References 56 publications

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“…PARP9 is a binding partner of Deltex 3-like, an E3 ubiquitin ligase that ubiquitinates histone H4 and protects cells against DNA damage. In the presence of its binding partner, PARP9 MARylates ubiquitin, preventing E3 ligase activity and providing regulation of the complex (46). The PARP9-Deltex 3-like complex also activates signal transducer and activator of transcription 1 (STAT1) and ubiquitinates histone proteins to promote the expression of a subset of interferonstimulated genes, thereby stimulating the innate immune response.…”

Section: Parps As Transcription Factor Coactivators/corepressorsmentioning

confidence: 99%

Poly(ADP-Ribose) Polymerases in Host-Pathogen Interactions, Inflammation, and Immunity

Brady

Goel

Johnson

2019

Microbiol Mol Biol Rev

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SUMMARYThe literature review presented here details recent research involving members of the poly(ADP-ribose) polymerase (PARP) family of proteins. Among the 17 recognized members of the family, the human enzyme PARP1 is the most extensively studied, resulting in a number of known biological and metabolic roles. This review is focused on the roles played by PARP enzymes in host-pathogen interactions and in diseases with an associated inflammatory response. In mammalian cells, several PARPs have specific roles in the antiviral response; this is perhaps best illustrated by PARP13, also termed the zinc finger antiviral protein (ZAP). Plant stress responses and immunity are also regulated by poly(ADP-ribosyl)ation. PARPs promote inflammatory responses by stimulating proinflammatory signal transduction pathways that lead to the expression of cytokines and cell adhesion molecules. Hence, PARP inhibitors show promise in the treatment of inflammatory disorders and conditions with an inflammatory component, such as diabetes, arthritis, and stroke. These functions are correlated with the biophysical characteristics of PARP family enzymes. This work is important in providing a comprehensive understanding of the molecular basis of pathogenesis and host responses, as well as in the identification of inhibitors. This is important because the identification of inhibitors has been shown to be effective in arresting the progression of disease.

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Section: Parps As Transcription Factor Coactivators/corepressorsmentioning

confidence: 99%

Poly(ADP-Ribose) Polymerases in Host-Pathogen Interactions, Inflammation, and Immunity

Brady

Goel

Johnson

2019

Microbiol Mol Biol Rev

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“…While the determinant for the high selectivity of bART for substrates is not clear (further discussed in Section 4), the ability of mammalian PARPs to modify a broad (but defined) subset of substrates could be partially dependent by protein-protein interactions, which could be responsible for substrate presentation to the enzyme. Such mechanism of substrate fishing has been demonstrated for PARP5a and PARP5b [153,154] as well as for PARP6 and PARP9 [108,155]. Same as for the specificity of PARPs in targeting well defined amino acids within protein substrates.…”

Section: Amino Acids Modified By Adprmentioning

confidence: 91%

“…Conversely, eukaryotic ARTD/ PARP group modifies a multitude of proteins targeting several amino acid residues through a selective mechanism that is still unknown. Amino acids modified by eukaryotic ARTD include serine (abbreviated as Ser-ADPr) and tyrosine (Tyr-ADPr) through O-glycosylation bonds [115,[143][144][145][146][147], negatively charged residues such as glutamic and aspartic amino acids through ester linkages [148,149], positively charged lysine through N-glycosidic bond [150], glycine as in the case of PARP9 [108] and cysteine as reported for PARP8 [43].…”

Section: Amino Acids Modified By Adprmentioning

confidence: 99%

“…Additional groups of human PARPs are the H-Y-I triad-containing enzymes (PARP6, PARP7, PARP8, PARP10, PARP11, and PARP12), the H-Y-Y-containing PARP16, the H-Y-L-containing PARP14 and PARP15, and the Q-Y-T/Y-Y-T-containing PARP9 and PARP13. With the exception of PARP13, which appears to be inactive [42,43,107], and of true poly(ADP-ribose) polymerases, the remaining human ARTD/PARP enzymes catalyse MARylation of their targets [43,108]. In addition, a divergent PARP-like enzyme containing the triad H-H-V belongs to a subgroup within the eukaryotic ARTD class [3,42] and it is referred as TpT1 or KptA (ARTD18).…”

Section: Introductionmentioning

confidence: 99%

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Targeting ADP-ribosylation as an antimicrobial strategy

Catara

Corteggio

Valente

et al. 2019

Biochemical Pharmacology

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A B S T R A C T ADP-ribosylation (ADPr) is an ancient reversible modification of cellular macromolecules controlling major biological processes as diverse as DNA damage repair, transcriptional regulation, intracellular transport, immune and stress responses, cell survival and proliferation. Furthermore, enzymatic reactions of ADPr are central in the pathogenesis of many human diseases, including infectious conditions. By providing a review of ADPr signalling in bacterial systems, we highlight the relevance of this chemical modification in the pathogenesis of human diseases depending on host-pathogen interactions. The post-antibiotic era has raised the need to find alternative approaches to antibiotic administration, as major pathogens becoming resistant to antibiotics. An in-depth understanding of ADPr reactions provides the rationale for designing novel antimicrobial strategies for treatment of infectious diseases. In addition, the understanding of mechanisms of ADPr by bacterial virulence factors offers important hints to improve our knowledge on cellular processes regulated by eukaryotic homologous enzymes, which are often involved in the pathogenesis of human diseases.T large number of worldwide spread diseases, affecting humans, insects and plants [31,[56][57][58], with a great impact on human health. In addition, infectious diseases strongly affect the world economy in terms of costs for the human health as well as food and agricultural economic losses [59]. The use of antibiotics to counteract the pathogen infections has represented the therapeutic strategy of choice in the last century, however the emergence of antibiotic resistance strains represents the major challenge of the 21st century [60][61][62]. Targeting bacterial pathogenic mechanisms by disarming pathogens of virulence factors, for instance by inhibiting the enzymatic activity of bART, represents a valid alternative intervention strategy to overcome antibiotic resistance [63][64][65][66]. In addition, because of the conservation of ADPr systems throughout the evolution, the understanding of bacterial pathogenic mechanisms may contribute to unveil novel and conserved cellular processes regulated by ADPr in high organisms [34,45,67,68]. The dysregulation of such processes can be either cause of human diseases or be target of therapeutic intervention [39,[69][70][71].Herein, we will provide a summary of bacterial ADPr systems describing their pathogenic mechanisms and highlighting the similarities with ADPr systems in mammals as well. Further, we discuss the potential of targeting ADPr for therapeutic strategies of infection diseases. ADP-ribosylation in pathophysiologyADPr was originally described in the 60s; two independent studies reported the identification of a new polymer, poly(ADP-ribose) (PAR) synthesised from NAD + in vertebrate cells [72] and, simultaneously, the finding that bacterial DTX activity from C. diphteriae is dependent on NAD + content [73]. In the following decades, research in the field has expanded the involvement of ADPr ...

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“…[13] Other studies show that Arg42 of Ub is ADP-ribosylated by af amily of effector proteins originating from Legionella pneumophila,t he pathogen causing Legionnaires disease. Ubiquitin (Ub), a7 6a mino acid residue long post-translational modifier itself,has recently been found to be modified with ADPr on different positions.T his cross-talk between ADP-ribosylation and ubiquitination is reported to have aregulatory effect on the DNArepair mechanism, where low levels of NADl ead to ubiquitination of histone protein H4, but high levels of NADl ead to ADP-ribosylation of Gly76; the C-terminus of Ub.…”

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confidence: 99%

A General Approach Towards Triazole‐Linked Adenosine Diphosphate Ribosylated Peptides and Proteins

et al. 2018

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Current methods to prepare adenosine diphosphate ribosylated (ADPr) peptides are not generally applicable due to the labile nature of this post-translational modification and its incompatibility with strong acidic conditions used in standards olid-phase peptide synthesis.Ageneral strategy is presented to prepare ADPr peptide analogues based on ac opper-catalyzed clickr eaction between an azide-modified peptide and an alkyne-modified ADPr counterpart. The scope of this approach was expanded to proteins by preparing two ubiquitin ADPr analogues carrying the biological relevant aglycosidic linkage.B iochemical validation using Legionella effector enzyme SdeA shows that clicked ubiquitin ADPr is well-tolerated and highlights the potential of this strategy to prepare ADPr proteins.

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Ubiquitin Modification by the E3 Ligase/ADP-Ribosyltransferase Dtx3L/Parp9

Cited by 178 publications

References 56 publications

Poly(ADP-Ribose) Polymerases in Host-Pathogen Interactions, Inflammation, and Immunity

Poly(ADP-Ribose) Polymerases in Host-Pathogen Interactions, Inflammation, and Immunity

Targeting ADP-ribosylation as an antimicrobial strategy

A General Approach Towards Triazole‐Linked Adenosine Diphosphate Ribosylated Peptides and Proteins

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