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Verlagsausgabe
DOI: 10.5445/IR/1000084135
Veröffentlicht am 07.11.2018
Originalveröffentlichung
DOI: 10.1093/nar/gkx1205
Scopus
Zitationen: 2
Web of Science
Zitationen: 1

The C-terminal domain of p53 orchestrates the interplay between non-covalent and covalent poly(ADP-ribosyl)ation of p53 by PARP1

Fischbach, Arthur; Krüger, Annika; Hampp, Stephanie; Assmann, Greta; Rank, Lisa; Hufnagel, Matthias; Stöckl, Martin T; Fischer, Jan M.F; Veith, Sebastian; Rossatti, Pascal; Ganz, Magdalena; Ferrando-May, Elisa; Hartwig, Andrea; Hauser, Karin; Wiesmüller, Lisa; Bürkle, Alexander; Mangerich, Aswin

Abstract:
The post-translational modification poly(ADPribosyl)ation (PARylation) plays key roles in genome maintenance and transcription. Both non-covalent poly(ADP-ribose) binding and covalent PARylation control protein functions, however, it is unknown how the two modes of modification crosstalk mechanistically. Employing the tumor suppressor p53 as a model substrate, this study provides detailed insights into the interplay between noncovalent and covalent PARylation and unravels its functional significance in the regulation of p53. We reveal that the multifunctional Cterminal domain (CTD) of p53 acts as the central hub in the PARylation-dependent regulation of p53. Specifically, p53 bound to auto-PARylated PARP1 via highly specific non–covalent PAR-CTD interaction, which conveyed target specificity for its covalent PARylation by PARP1. Strikingly, fusing the p53-CTD to a protein that is normally not PARylated, renders this a target for covalent PARylation as well. Functional studies revealed that the p53–PAR interaction had substantial implications on molecular and cellular levels. Thus, PAR significantly influenced the complex p53–DNA bin ... mehr


Zugehörige Institution(en) am KIT Institut für Angewandte Biowissenschaften (IAB)
Publikationstyp Zeitschriftenaufsatz
Jahr 2018
Sprache Englisch
Identifikator ISSN: 0305-1048, 1362-4962
URN: urn:nbn:de:swb:90-841354
KITopen ID: 1000084135
Erschienen in Nucleic acids research
Band 46
Heft 2
Seiten 804–822
Vorab online veröffentlicht am 04.12.2017
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