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Keywords = ADP ribose glycohydrolases (ARH)

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25 pages, 1687 KiB  
Review
ADP-Ribosylation as Post-Translational Modification of Proteins: Use of Inhibitors in Cancer Control
by Palmiro Poltronieri, Masanao Miwa and Mitsuko Masutani
Int. J. Mol. Sci. 2021, 22(19), 10829; https://doi.org/10.3390/ijms221910829 - 7 Oct 2021
Cited by 11 | Viewed by 6385
Abstract
Among the post-translational modifications of proteins, ADP-ribosylation has been studied for over fifty years, and a large set of functions, including DNA repair, transcription, and cell signaling, have been assigned to this post-translational modification (PTM). This review presents an update on the function [...] Read more.
Among the post-translational modifications of proteins, ADP-ribosylation has been studied for over fifty years, and a large set of functions, including DNA repair, transcription, and cell signaling, have been assigned to this post-translational modification (PTM). This review presents an update on the function of a large set of enzyme writers, the readers that are recruited by the modified targets, and the erasers that reverse the modification to the original amino acid residue, removing the covalent bonds formed. In particular, the review provides details on the involvement of the enzymes performing monoADP-ribosylation/polyADP-ribosylation (MAR/PAR) cycling in cancers. Of note, there is potential for the application of the inhibitors developed for cancer also in the therapy of non-oncological diseases such as the protection against oxidative stress, the suppression of inflammatory responses, and the treatment of neurodegenerative diseases. This field of studies is not concluded, since novel enzymes are being discovered at a rapid pace. Full article
(This article belongs to the Special Issue Protein Post-translational Modification in Human Diseases)
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4 pages, 174 KiB  
Editorial
Emerging Concepts on the Role of ADP-Ribosylation
by Palmiro Poltronieri
Challenges 2020, 11(1), 3; https://doi.org/10.3390/challe11010003 - 19 Feb 2020
Viewed by 2697
Abstract
NAD+ has emerged as a crucial element in both bioenergetic and signaling pathways, since it acts as a key regulator of cellular and organism homeostasis. NAD+ is a coenzyme in redox reactions, a donor of adenosine diphosphate-ribose (ADPr) moieties in ADP-ribosylation [...] Read more.
NAD+ has emerged as a crucial element in both bioenergetic and signaling pathways, since it acts as a key regulator of cellular and organism homeostasis. NAD+ is a coenzyme in redox reactions, a donor of adenosine diphosphate-ribose (ADPr) moieties in ADP-ribosylation reactions, and a substrate for sirtuins, a group of histone deacetylase enzymes that use NAD+ to remove acetyl groups from proteins. NAD+ is also a precursor of cyclic ADP-ribose, a second messenger in the release and signaling of Ca++, and of diadenosine tetraphosphate (Ap4A) and oligoadenylates (oligo2′-5′A)—two immune response-activating compounds. In the biological systems considered in this review, NAD+ is mostly consumed in ADP-ribose (ADPr) transfer reactions. In this review, the roles of these chemical products are discussed in biological systems, such as in animals, plants, fungi and bacteria. In the review, ADP-ribosylating enzymes are introduced, as well as the importance to restore the NAD+ pools in these systems. Finally, a special attention is presently focused on viral macrodomains, aimed to develop inhibitors to improve the immune response to viruses. Full article
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