PARPs and ADP-ribosylation: Deciphering the complexity with molecular tools

Dasovich, Morgan; Leung, Anthony Kwan

doi:10.1016/j.molcel.2023.04.009

Cited by 19 publications

(13 citation statements)

References 165 publications

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“…What sets ADPr apart is its diverse conjugation sites, with the modification reported on nine amino acids (CDEHKRSTY) across thousands of human proteins. 3 …”

Section: Main Textmentioning

confidence: 99%

Molecular tools unveil distinct waves of ADP-ribosylation during DNA repair

Dasovich

Leung

2023

Cell Reports Methods

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“…What sets ADPr apart is its diverse conjugation sites, with the modification reported on nine amino acids (CDEHKRSTY) across thousands of human proteins. 3 …”

Section: Main Textmentioning

confidence: 99%

Molecular tools unveil distinct waves of ADP-ribosylation during DNA repair

Dasovich

Leung

2023

Cell Reports Methods

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“…Over the past decades, many protocols and techniques have been developed for interrogating the cell biology; for an overview of the main methodologies and techniques used for studying these enzymes, the readers are directed to the following reviews [81,124,125].…”

Section: Specific Inhibitors As Precious Chemical Probesmentioning

confidence: 99%

Privileged Scaffolds for Potent and Specific Inhibitors of Mono-ADP-Ribosylating PARPs

Nizi,

Sarnari,

Tabarrini

2023

Molecules

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The identification of new targets to address unmet medical needs, better in a personalized way, is an urgent necessity. The introduction of PARP1 inhibitors into therapy, almost ten years ago, has represented a step forward this need being an innovate cancer treatment through a precision medicine approach. The PARP family consists of 17 members of which PARP1 that works by poly-ADP ribosylating the substrate is the sole enzyme so far exploited as therapeutic target. Most of the other members are mono-ADP-ribosylating (mono-ARTs) enzymes, and recent studies have deciphered their pathophysiological roles which appear to be very extensive with various potential therapeutic applications. In parallel, a handful of mono-ARTs inhibitors emerged that have been collected in a perspective on 2022. After that, additional very interesting compounds were identified highlighting the hot-topic nature of this research field and prompting an update. From the present review, where we have reported only mono-ARTs inhibitors endowed with the appropriate profile of pharmacological tools or drug candidate, four privileged scaffolds clearly stood out that constitute the basis for further drug discovery campaigns.

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“…The susbtrates can be modified by ADPribose chains of varying lengths and chemical structures, i.e. by either a single ADP-ribose unit (monoADPRylation or MAR) or polymers of ADP-ribose units (polyADPRylation or PAR), which serve to alter biochemical activities of the substrate protein or drive protein-protein interactions through new interaction surfaces [1][2][3][4][5].…”

Section: Introductionmentioning

confidence: 99%

Development and Characterization of Recombinant ADP-Ribose Binding Reagents that Allow Simultaneous Detection of Mono and Poly ADP-Ribose

Chiu,

Camacho,

Kraus

2024

Preprint

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ADP-ribosylation (ADPRylation) is a post-translational modification (PTM) of proteins mediated by the activity of a variety of ADP-ribosyltransferase (ART) enzymes, such as the Poly(ADP-ribose) Polymerase (PARP) family of proteins. This PTM is diverse in both form and biological functions, which makes it a highly interesting modification, but difficult to study due to limitations in reagents available to detect the diversity of ADP-ribosylation. Recently we developed a set of recombinant antibody-like ADP-ribose binding proteins, using naturally occurring ADPR binding domains (ARBDs) that include macrodomains and WWE domains, that have been functionalized by fusion to the constant Fc region of rabbit immunoglobulin. Herein, we present an expansion of this biological toolkit, where we have replaced the rabbit Fc sequence with two other species, the Fc for mouse and goat immunogloblulin. Characterization of the new reagents indicates that they can be detected in a species-dependent manner, recognize specific ADP-ribose moieties, and excitingly, can be used in various antibody-based assays by co-staining. The expansion of this tool will allow for more multiplexed assessments of the complexity of ADPRylation biology in many biological systems.

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PARPs and ADP-ribosylation: Deciphering the complexity with molecular tools

Cited by 19 publications

References 165 publications

Molecular tools unveil distinct waves of ADP-ribosylation during DNA repair

Molecular tools unveil distinct waves of ADP-ribosylation during DNA repair

Privileged Scaffolds for Potent and Specific Inhibitors of Mono-ADP-Ribosylating PARPs

Development and Characterization of Recombinant ADP-Ribose Binding Reagents that Allow Simultaneous Detection of Mono and Poly ADP-Ribose

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