ArticleMolecular and cellular biology2008
Regulation of p53 target gene expression by peptidylarginine deiminase 4.
Article in Molecular and cellular biology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 135 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
135 citing papers in PubMed, 1 synthesis or guideline pooled it, 221 citations in OpenAlex.
- Role of the PADI family in inflammatory autoimmune diseases and cancers: A systematic review.Frontiers in immunology · 2023Pooled it
- Peptidylarginine Deiminases: An Overview of Recent Advances in Citrullination Research.International journal of molecular sciences · 2025Review
- Citrullination negatively regulates the functions of the p53 protein and opposes its ubiquitination and degradation.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Targeted citrullination enables p53 binding to non-canonical sites.Molecular cell · 2025Article
- Citrullination in health and disease: From physiological function to gene regulation.Genes & diseases · 2025Review
- Therapeutic implication of oxidative stress-induced growth inhibitor 1 (OSGIN1) in cancer.Oncogene · 2025Review
- Citrullination at the N-terminal region of MDM2 by the PADI4 enzyme.Protein science : a publication of the Protein Society · 2025Article
- NUPR1 contributes to endocrine therapy resistance by modulating BIRC5 expression and inducing luminal B-ERBB2Journal of Cancer · 2025Article
- Discovering covalent cyclic peptide inhibitors of peptidyl arginine deiminase 4 (PADI4) using mRNA-display with a genetically encoded electrophilic warhead.Communications chemistry · 2024Article
- Neutrophil-derived PAD4 induces citrullination of CKMT1 exacerbates mucosal inflammation in inflammatory bowel disease.Cellular & molecular immunology · 2024Article
- Article
- Hypoxia-induced epigenetic regulation of breast cancer progression and the tumour microenvironment.Frontiers in cell and developmental biology · 2024Review
- PAD-mediated citrullination is a novel candidate diagnostic marker and druggable target for HPV-associated cervical cancer.Frontiers in cellular and infection microbiology · 2024Article
- Citrullination and the protein code: crosstalk between post-translational modifications in cancer.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2023Review
- Recent advances in characterization of citrullination and its implication in human disease research: From method development to network integration.Proteomics · 2023Review
- Inhibition of CARM1 suppresses proliferation of multiple myeloma cells through activation of p53 signaling pathway.Molecular biology reports · 2023Article
- New insights into cancer: MDM2 binds to the citrullinating enzyme PADI4.Protein science : a publication of the Protein Society · 2023Article
- An African-Specific Variant of TP53 Reveals PADI4 as a Regulator of p53-Mediated Tumor Suppression.Cancer discovery · 2023Article
- Advances in the Mechanism of Action of Neutrophil Extracellular Traps in Gastrointestinal Tumors: A Review.International journal of general medicine · 2023Article
- Metabolic reprogramming and epigenetic modifications on the path to cancer.Protein & cell · 2022Review
75 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
Histone Arg methylation has been correlated with transcriptional activation of p53 target genes. However, whether this modification is reversed to repress the expression of p53 target genes is unclear. Here, we report that peptidylarginine deiminase 4, a histone citrullination enzyme, is involved in the repression of p53 target genes. Inhibition or depletion of PAD4 elevated the expression of a subset of p53 target genes, including p21/CIP1/WAF1, leading to cell cycle arrest and apoptosis. Moreover, the induction of p21, cell cycle arrest, and apoptosis by PAD4 depletion is p53 dependent. Protein-protein interaction studies showed an interaction between p53 and PAD4. Chromatin immunoprecipitation assays showed that PAD4 is recruited to the p21 promoter in a p53-dependent manner. RNA polymerase II (Pol II) activities and the association of PAD4 are dynamically regulated at the p21 promoter during UV irradiation. Paused RNA Pol II and high levels of PAD4 were detected before UV treatment. At early time points after UV treatment, an increase of histone Arg methylation and a decrease of citrullination were correlated with a transient activation of p21. At later times after UV irradiation, a loss of RNA Pol II and an increase of PAD4 were detected at the p21 promoter. The dynamics of RNA Pol II activities after UV treatment were further corroborated by permanganate footprinting. Together, these results suggest a role of PAD4 in the regulation of p53 target gene expression.
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Registered trials
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.