New players to the field of ADP-ribosylation make the final cut - PubMed (original) (raw)
Comment
New players to the field of ADP-ribosylation make the final cut
Jamin D Steffen et al. EMBO J. 2013.
Abstract
EMBO J (2013) 32 9, 1225–1237. doi:; DOI: 10.1038/emboj.2013.51
ADP-ribose-based intermediates, including PARP-generated mono- and poly(ADP-ribose) post-translational modifications, are important to a number of cellular signalling processes. The reversal of poly(ADP-ribosyl)ation is mostly attributed to PARG, which however cannot remove the final protein-linked mono(ADP-ribose) residue. Three recent studies, one of them in The EMBO Journal, now report that certain macrodomains remove terminal ADP-ribose modifications from acidic residues.
Conflict of interest statement
The authors declare that they have no conflict of interest.
Figures
Figure 1
Pathway of reversible protein modification reactions that involve NAD+ consumption. Consumption of NAD+ through nicotinamide cleavage drives the catalysis of mono- and poly(ADP-ribosyl)ation of proteins by ADP-ribosyl transferases, as well as deacetylation of proteins by Sirtuins. Formation of these modifications is important to various cell signalling events such as DNA repair, chromatin remodelling, transcription, telomere homeostasis, and cell death. ADP-ribose modifications are short-lived due to the activity of hydrolase enzymes reversing the modification to yield ADP-ribose. The recently identified macrodomains C6orf130/TARG, MacroD1, and MacroD2 now fill in previously unidentified roles of ADP-ribose and PAR hydrolysis from acidic residues.
Comment on
- Deficiency of terminal ADP-ribose protein glycohydrolase TARG1/C6orf130 in neurodegenerative disease.
Sharifi R, Morra R, Appel CD, Tallis M, Chioza B, Jankevicius G, Simpson MA, Matic I, Ozkan E, Golia B, Schellenberg MJ, Weston R, Williams JG, Rossi MN, Galehdari H, Krahn J, Wan A, Trembath RC, Crosby AH, Ahel D, Hay R, Ladurner AG, Timinszky G, Williams RS, Ahel I. Sharifi R, et al. EMBO J. 2013 May 2;32(9):1225-37. doi: 10.1038/emboj.2013.51. Epub 2013 Mar 12. EMBO J. 2013. PMID: 23481255 Free PMC article.
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