ArticleNucleic acids research2018
The C-terminal domain of p53 orchestrates the interplay between non-covalent and covalent poly(ADP-ribosyl)ation of p53 by PARP1.
Article in Nucleic acids research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers.
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Who cites it
69 citing papers in PubMed, 113 citations in OpenAlex.
- ROS-ATM-CBP axis-mediated PARP1 lactylation aggravates doxorubicin-induced cardiotoxicity.Clinical and translational medicine · 2026Article
- Noncovalent PAR Binding Guides Proteins to PARP1-Mediated PARylation.ACS chemical biology · 2026Article
- PARylation-centric crosstalk: orchestrating immune evasion and multidrug resistance in ovarian cancer.Frontiers in immunology · 2026Review
- Investigating the functions and molecular mechanisms of DTX3L in cancer progression.Frontiers in oncology · 2026Review
- Review
- Ubiquitin E3 Ligases and p53 in Doxorubicin-Induced Cardiotoxicity.International journal of molecular sciences · 2025Review
- Deciphering the dark side of histone ADP-ribosylation: what structural features of damaged nucleosome regulate the activities of PARP1 and PARP2.Nucleic acids research · 2025Article
- Molecular Targets for Pharmacotherapy of Head and Neck Squamous Cell Carcinomas.Current issues in molecular biology · 2025Review
- Proteome-wide microarray-based screening of PAR-binding proteins.Nucleic acids research · 2025Article
- p53-deficient cancer cells hyperactivate DNA double-strand break repair pathways to overcome chemotherapeutic damage and augment survival.Molecular biology reports · 2025Article
- Nicotinamide mononucleotide combined with PJ-34 protects microglial cells from lipopolysaccharide-induced mitochondrial impairment through NMNAT3-PARP1 axis.Journal of translational medicine · 2025Article
- PARPs and ADP-ribosylation-mediated biomolecular condensates: determinants, dynamics, and disease implications.Trends in biochemical sciences · 2025Review
- Prognostic Significance of S100A4 in Ovarian Clear Cell Carcinoma: Its Relation to Tumor Progression and Chemoresistance.Cancers · 2025Article
- Adenosine diphosphate-ribosylation greatly affects proteins function: a focus on neurodegenerative diseases.Frontiers in aging neuroscience · 2025Review
- SART1 modulates poly-(ADP-ribose) chain accumulation and PARP1 chromatin localization.iScience · 2024Article
- p53-dependent crosstalk between DNA replication integrity and redox metabolism mediated through a NRF2-PARP1 axis.Nucleic acids research · 2024Article
- Poly (ADP-ribose) polymerase 1 promotes HuR/ELAVL1 cytoplasmic localization and inflammatory gene expression by regulating p38 MAPK activity.Cellular and molecular life sciences : CMLS · 2024Article
- Targeting tumor suppressor p53 for organ fibrosis therapy.Cell death & disease · 2024Review
- Mono-ADP-ribosylation, a MARylationmultifaced modification of protein, DNA and RNA: characterizations, functions and mechanisms.Cell death discovery · 2024Review
- The AsiDNA™ decoy mimicking DSBs protects the normal tissue from radiation toxicity through a DNA-PK/p53/p21-dependent G1/S arrest.NAR cancer · 2024Article
9 more citing papers are in PubMed but not listed here.
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Authors and funding
17 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The post-translational modification poly(ADP-ribosyl)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 non-covalent and covalent PARylation and unravels its functional significance in the regulation of p53. We reveal that the multifunctional C-terminal 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 binding properties and controlled p53 functions, with major implications on the p53-dependent interactome, transcription, and replication-associated recombination. Remarkably, this mechanism potentially also applies to other PARylation targets, since a bioinformatics analysis revealed that CTD-like regions are highly enriched in the PARylated proteome.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.