Processing of protein ADP-ribosylation by Nudix hydrolases.
Luca Palazzo,Benjamin Thomas,Ann-Sofie Jemth,Thomas Colby,Orsolya Leidecker,Karla L. H. Feijs,Roko Zaja,Olga Loseva,Jordi Carreras Puigvert,Ivan Matic,Thomas Helleday,Ivan Ahel +11 more
TLDR
Human Nudix (nucleoside diphosphate-linked moiety X)-type motif 16 (hNUDT16) represents a new enzyme class that can process protein ADP-ribosylation in vitro, converting it into ribose-5'-phosphate (R5P) tags covalently attached to the modified proteins.Abstract:
ADP-ribosylation is a post-translational modification (PTM) of proteins found in organisms from all kingdoms of life which regulates many important biological functions including DNA repair, chromatin structure, unfolded protein response and apoptosis. Several cellular enzymes, such as macrodomain containing proteins PARG [poly(ADP-ribose) glycohydrolase] and TARG1 [terminal ADP-ribose (ADPr) protein glycohydrolase], reverse protein ADP-ribosylation. In the present study, we show that human Nudix (nucleoside diphosphate-linked moiety X)-type motif 16 (hNUDT16) represents a new enzyme class that can process protein ADP-ribosylation in vitro , converting it into ribose-5′-phosphate (R5P) tags covalently attached to the modified proteins. Furthermore, our data show that hNUDT16 enzymatic activity can be used to trim ADP-ribosylation on proteins in order to facilitate analysis of ADP-ribosylation sites on proteins by MS.read more
Citations
More filters
Journal ArticleDOI
PARPs and ADP-ribosylation: recent advances linking molecular functions to biological outcomes
TL;DR: New findings on the diverse roles of PARPs in chromatin regulation, transcription, RNA biology, and DNA repair have been complemented by recent advances that link ADP-ribosylation to stress responses, metabolism, viral infections, and cancer.
MTH1 inhibition eradicates cancer by preventing sanitation of the dNTP pool - Supporting Information
Helge Gad,Tobias Koolmeister,Ann-Sofie Jemth,Saeed Eshtad,Sylvain A. Jacques,Cecilia E. Ström,Linda M. Svensson,Niklas Schultz,Thomas Lundbäck,Berglind Osk Einarsdottir,Aljona Saleh,Camilla Göktürk,Pawel Baranczewski,Richard Svensson,Ronnie P.-A. Berntsson,Robert Gustafsson,Kia Strömberg,Kumar Sanjiv,Marie-Caroline Jacques-Cordonnier,Matthieu Desroses,Anna-Lena Gustavsson,Roger Olofsson,Fredrik Johansson,Evert Homan,Olga Loseva,Lars Hammarström +25 more
TL;DR: In this paper, the authors validate MTH1 as an anticancer target in vivo and describe small molecules TH287 and TH588 as first-in-class nudix hydrolase family inhibitors that potently and selectively engage and inhibit the MTH 1 protein in cells.
Journal ArticleDOI
Serine ADP-Ribosylation Depends on HPF1
Juan José Bonfiglio,Pietro Fontana,Qi Zhang,Thomas Colby,Ian Gibbs-Seymour,Ilian Atanassov,Edward Bartlett,Roko Zaja,Ivan Ahel,Ivan Matic +9 more
TL;DR: It is reported that serine ADPr is strictly dependent on histone PARylation factor 1 (HPF1), a recently identified regulator of PARP-1, and proposed that O-linked protein AD Pr is the key signal in PARP/PARP-2-dependent processes that govern genome stability.
Journal ArticleDOI
Insights into the biogenesis, function, and regulation of ADP-ribosylation.
Michael S. Cohen,Paul Chang +1 more
TL;DR: The functions of amino acid ADPr modifications and the ART proteins that make them, the nature of the chemical linkage between ADPr and its targets and how this impacts function and stability, and the way that ARTs select specific amino acids in targets to modify are discussed.
Journal ArticleDOI
Phosphoribosylation of Ubiquitin Promotes Serine Ubiquitination and Impairs Conventional Ubiquitination
Sagar Bhogaraju,Sissy Kalayil,Yaobin Liu,Florian Bonn,Thomas Colby,Ivan Matic,Ivan Dikic,Ivan Dikic +7 more
TL;DR: A phosphodiesterase domain in SdeA is identified that efficiently catalyzes phosphoribosylation of ubiquitin on a specific arginine via an ADP-ribose-ubiquitin intermediate and it is proposed that phosphorIBosylations of ubiqu itin potently modulates ubiquit in mammalian cells.
References
More filters
Journal ArticleDOI
A cross-platform toolkit for mass spectrometry and proteomics
Matthew C. Chambers,Brendan MacLean,Robert Burke,Dario Amodei,Daniel Ruderman,Steffen Neumann,Laurent Gatto,Bernd Fischer,Brian S. Pratt,Jarrett D. Egertson,Katherine Hoff,Darren Kessner,Natalie Tasman,Nicholas J. Shulman,Barbara Frewen,Tahmina A Baker,Mi-Youn Brusniak,Christopher Paulse,David M. Creasy,Lisa Flashner,Kian Kani,Chris Moulding,Sean L. Seymour,Lydia M. Nuwaysir,Brent Lefebvre,Frank E. Kuhlmann,Joe Roark,Paape Rainer,Suckau Detlev,Tina Hemenway,Andreas Huhmer,James I. Langridge,Brian Connolly,Trey Chadick,Krisztina Holly,Josh Eckels,Eric W. Deutsch,Robert L. Moritz,Jonathan E. Katz,David B. Agus,Michael J. MacCoss,David L. Tabb,Parag Mallick,Parag Mallick +43 more
TL;DR: The ProteoWizard Toolkit is developed, a robust set of open-source, software libraries and applications designed to facilitate proteomics research that implements the first-ever, non-commercial, unified data access interface for proteomics, bridging field-standard open formats and all common vendor formats.
Journal ArticleDOI
Poly(adp-ribosyl)ation reactions in the regulation of nuclear functions
TL;DR: The total dependence of poly(ADP-ribose) synthesis on DNA strand breaks strongly suggests that this post-translational modification is involved in the metabolism of nucleic acids, and the presence of PARP in these multiprotein complexes clearly supports an important role for poly(ADE-ribosyl)ation reactions in DNA transactions.
Journal ArticleDOI
The PARP superfamily.
TL;DR: This review summarizes the present knowledge of this emerging superfamily of Poly(ADP‐ribose) polymerases, which might ultimately improve pharmacological strategies to enhance both antitumor efficacy and the treatment of a number of inflammatory and neurodegenerative disorders.
Journal ArticleDOI
New insights into the molecular and cellular functions of poly(ADP-ribose) and PARPs.
Bryan A. Gibson,W. Lee Kraus +1 more
TL;DR: This work has shown that the activity of PARP family members, such as PARP1 and PARP2, is tied to cellular signalling pathways, and through poly(ADP-ribosyl)ation (PARylation) they ultimately promote changes in gene expression, RNA and protein abundance, and the location and activity of proteins that mediate signalling responses.
Journal ArticleDOI
A malachite green procedure for orthophosphate determination and its use in alkaline phosphatase-based enzyme immunoassay.
TL;DR: An improved procedure for phosphate determination based on a highly colored complex of phosphomolybdate and malachite green is described, resulting in a 4-fold increase in sensitivity and a 20-fold gain in sensitivity in terms of absorbance readings compared to the standard method based on rho-nitrophenol measurement.
Related Papers (5)
Deficiency of terminal ADP‐ribose protein glycohydrolase TARG1/C6orf130 in neurodegenerative disease
Reza Sharifi,Rosa Morra,C. Denise Appel,Michael Tallis,Barry A. Chioza,Gytis Jankevicius,Michael A. Simpson,Ivan Matic,Ege Ozkan,Barbara Golia,Matthew J. Schellenberg,Ria Weston,Jason Williams,Marianna Nicoletta Rossi,Hamid Galehdari,Juno M. Krahn,Y. B. Alexander Wan,Richard C. Trembath,Andrew H. Crosby,Dragana Ahel,Ronald T. Hay,Andreas G. Ladurner,Andreas G. Ladurner,Gyula Timinszky,R. Scott Williams,Ivan Ahel +25 more