title: Processing of protein ADP-ribosylation by Nudix hydrolases.
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.
authors: *Sir William Dunn School of Pathology, University of Oxford, Oxford, OX1 3RE, U.K.
authors: Luca
authors: L
authors: Palazzo
authors: *Sir William Dunn School of Pathology, University of Oxford, Oxford, OX1 3RE, U.K.
authors: Benjamin
authors: B
authors: Thomas
authors: †Science for Life Laboratory, Division of Translational Medicine and Chemical Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, S-171 21 Stockholm, Sweden.
authors: Ann-Sofie
authors: AS
authors: Jemth
authors: ‡Max Planck Institute for Biology of Ageing, Joseph-Stelzmann-Street 9b, D-50931 Köln/Cologne, Germany.
authors: Thomas
authors: T
authors: Colby
authors: ‡Max Planck Institute for Biology of Ageing, Joseph-Stelzmann-Street 9b, D-50931 Köln/Cologne, Germany.
authors: Orsolya
authors: O
authors: Leidecker
authors: *Sir William Dunn School of Pathology, University of Oxford, Oxford, OX1 3RE, U.K.
authors: Karla L H
authors: KL
authors: Feijs
authors: *Sir William Dunn School of Pathology, University of Oxford, Oxford, OX1 3RE, U.K.
authors: Roko
authors: R
authors: Zaja
authors: †Science for Life Laboratory, Division of Translational Medicine and Chemical Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, S-171 21 Stockholm, Sweden.
authors: Olga
authors: O
authors: Loseva
authors: †Science for Life Laboratory, Division of Translational Medicine and Chemical Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, S-171 21 Stockholm, Sweden.
authors: Jordi Carreras
authors: JC
authors: Puigvert
authors: ‡Max Planck Institute for Biology of Ageing, Joseph-Stelzmann-Street 9b, D-50931 Köln/Cologne, Germany.
authors: Ivan
authors: I
authors: Matic
authors: †Science for Life Laboratory, Division of Translational Medicine and Chemical Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, S-171 21 Stockholm, Sweden.
authors: Thomas
authors: T
authors: Helleday
authors: *Sir William Dunn School of Pathology, University of Oxford, Oxford, OX1 3RE, U.K.
authors: Ivan
authors: I
authors: Ahel
mesh_terms: D000595:Amino Acid Sequence; D006031:Glycosylation; D006801:Humans; D015151:Immunoblotting; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009154:Mutation / Q000235:genetics; D011064:Poly Adenosine Diphosphate Ribose / Q000378:metabolism*; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D011755:Pyrophosphatases / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D000096964:Nudix Hydrolases
chemical_list: D011064:Poly Adenosine Diphosphate Ribose; D011065:Poly(ADP-ribose) Polymerases; D011755:Pyrophosphatases; D000096964:Nudix Hydrolases