Proteome-wide identification of poly(ADP-Ribosyl)ation targets in different genotoxic stress responses

Poly(ADP-ribos)ylation (PARylation) is a reversible posttranslational modification found in higher eukaryotes. However, little is known about PARylation acceptor proteins. Here, we describe a sensitive proteomics approach based on high-accuracy quantitative mass spectrometry for the identification o...

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Vydáno v:	Molecular cell Ročník 52; číslo 2; s. 272
Hlavní autoři:	Jungmichel, Stephanie, Rosenthal, Florian, Altmeyer, Matthias, Lukas, Jiri, Hottiger, Michael O, Nielsen, Michael L
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	United States 24.10.2013
Témata:	Antineoplastic Agents, Alkylating - pharmacology Cell Line, Tumor Cell Nucleus - genetics Cell Nucleus - metabolism Chromatography, Liquid DNA Damage DNA-Binding Proteins - genetics DNA-Binding Proteins - metabolism Electrophoresis, Polyacrylamide Gel Green Fluorescent Proteins - genetics Green Fluorescent Proteins - metabolism HeLa Cells Humans Hydrogen Peroxide - pharmacology Methyl Methanesulfonate - pharmacology Microscopy, Confocal Nuclear Proteins - genetics Nuclear Proteins - metabolism Oxidants - pharmacology Poly Adenosine Diphosphate Ribose - metabolism Protein Processing, Post-Translational - drug effects Protein Processing, Post-Translational - radiation effects Proteome - genetics Proteome - metabolism Proteomics - methods Radiation, Ionizing RNA Interference Signal Transduction - drug effects Signal Transduction - genetics Signal Transduction - radiation effects Tandem Mass Spectrometry TATA-Binding Protein Associated Factors - genetics TATA-Binding Protein Associated Factors - metabolism Transcription Factors - genetics Transcription Factors - metabolism
ISSN:	1097-4164, 1097-4164
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Shrnutí:	Poly(ADP-ribos)ylation (PARylation) is a reversible posttranslational modification found in higher eukaryotes. However, little is known about PARylation acceptor proteins. Here, we describe a sensitive proteomics approach based on high-accuracy quantitative mass spectrometry for the identification of PARylated proteins induced under different cellular stress conditions. While confirming the majority of known PARylated substrates, our screen identifies numerous additional PARylation targets. In vivo and in vitro validation of acceptor proteins confirms that our methodology targets covalent PARylation. Nuclear proteins encompassing nucleic acid binding properties are prominently PARylated upon genotoxic stress, consistent with the nuclear localization of ARTD1/PARP1 and ARTD2/PARP2. Distinct differences in proteins becoming PARylated upon various genotoxic insults are observed, exemplified by the PARylation of RNA-processing factors THRAP3 and TAF15 under oxidative stress. High-content imaging reveals that PARylation affects the nuclear relocalization of THRAP3 and TAF15, demonstrating the potential of our approach to uncover hitherto unappreciated processes being controlled by specific genotoxic-stress-induced PARylation.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1097-4164 1097-4164
DOI:	10.1016/j.molcel.2013.08.026