ArticleThe Journal of biological chemistry2011
Citrullination of inhibitor of growth 4 (ING4) by peptidylarginine deminase 4 (PAD4) disrupts the interaction between ING4 and p53.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.
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Who cites it
64 citing papers in PubMed, 123 citations in OpenAlex.
- Roles of peptidylarginine deiminase (PAD) and protein citrullination in viral infections.Frontiers in microbiology · 2026Review
- Peptidylarginine Deiminases: An Overview of Recent Advances in Citrullination Research.International journal of molecular sciences · 2025Review
- Context-dependent contribution of peptidyl arginine deiminase 4 (PAD4) to neutrophil extracellular trap formation and liver injury in acute and chronic hepatotoxicant challenge.Toxicological sciences : an official journal of the Society of Toxicology · 2025Article
- 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
- Citrullination in health and disease: From physiological function to gene regulation.Genes & diseases · 2025Review
- 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
- Neutrophil attachment via Mac-1 (Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2023Article
- Role of non-canonical post-translational modifications in gastrointestinal tumors.Cancer cell international · 2023Review
- Citrullination Post-Translational Modification: State of the Art of Brain Tumor Investigations and Future Perspectives.Diagnostics (Basel, Switzerland) · 2023Review
- Peptidylarginine deiminase 2 plays a key role in osteogenesis by enhancing RUNX2 stability through citrullination.Cell death & disease · 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
- PADs and NETs in digestive system: From physiology to pathology.Frontiers in immunology · 2023Review
- PAD4 and Its Inhibitors in Cancer Progression and Prognosis.Pharmaceutics · 2022Review
- PAD4-dependent citrullination of nuclear translocation of GSK3β promotes colorectal cancer progression via the degradation of nuclear CDKN1A.Neoplasia (New York, N.Y.) · 2022Article
- CXCL1-Triggered PAD4 Cytoplasmic Translocation Enhances Neutrophil Adhesion through Citrullination of PDIA1.Journal of atherosclerosis and thrombosis · 2022Article
- Intrinsic function of the peptidylarginine deiminase PADI4 is dispensable for normal haematopoiesis.Biology open · 2022Article
- The virtues and vices of protein citrullination.Royal Society open science · 2022Review
- 12-Plex DiLeu Isobaric Labeling Enabled High-Throughput Investigation of Citrullination Alterations in the DNA Damage Response.Analytical chemistry · 2022Article
- Citrullination Was Introduced into Animals by Horizontal Gene Transfer from Cyanobacteria.Molecular biology and evolution · 2022Article
4 more citing papers are in PubMed but not listed here.
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Gene expression is regulated by a number of interrelated posttranslational modifications of histones, including citrullination. For example, peptidylarginine deminase 4 (PAD4) converts peptidyl arginine to citrulline in histone H3 and can repress gene expression. However, regulation of gene expression through citrullination of non-histone proteins is less well defined. Herein, we identify a tumor suppressor protein, inhibitor of growth 4 (ING4), as a novel non-histone substrate of PAD4. ING4 is known to bind p53 via its nuclear localization signal (NLS) region and to enhance transcriptional activity of p53. We show that PAD4 preferentially citrullinates ING4 in the same NLS region and thereby disrupts the interaction between ING4 and p53. A citrulline-mimicking Arg-NLS-Gln ING4 mutant, which has all Arg residues in the NLS mutated to Gln, loses its affinity for p53, can no longer promote p53 acetylation, and results in repression of downstream p21 expression. In addition, we found that citrullination leads to increased susceptibility of ING4 to degradation, likely impacting p53-independent pathways as well. These findings elucidate an interaction between posttranslational citrullination, acetylation, and methylation and highlight an unusual mechanism whereby citrullination of a non-histone protein impacts gene regulation.
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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.