ArticleCancer discovery2023
An African-Specific Variant of TP53 Reveals PADI4 as a Regulator of p53-Mediated Tumor Suppression.
Article in Cancer discovery, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 28 citations in OpenAlex.
- Variation at the R181 Residue of p53 Confers Loss of p53 DNA Binding Cooperativity with the Retention of Mitochondria-Associated Apoptosis.Molecular cancer research : MCR · 2026Article
- The TP53 gene contains a diversity box that makes it more than a tumor suppressor.Cell death and differentiation · 2026Review
- A Personalized Therapeutic Approach for Liver Cancers Expressing the African-Centric P47S Variant of TP53.Molecular cancer research : MCR · 2026Article
- Article
- Mutant p53 binds and controls estrogen receptor activity to drive endocrine resistance in ovarian cancer.Genes & development · 2026Article
- Moving Beyond Somatic Alterations: Uncovering the Germline Basis of Myeloid Malignancies.Cancers · 2026Review
- Citrullination in Tumor Metastasis, Inside and Outside the Cells.Cancer science · 2025Review
- Integrative multiomic approaches reveal ZMAT3 and p21 as conserved hubs in the p53 tumor suppression network.Cell death and differentiation · 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
- Targeted citrullination enables p53 binding to non-canonical sites.Molecular cell · 2025Article
- Harnessing p53 for targeted cancer therapy: new advances and future directions.Transcription · 2025Review
- Clustering ofiScience · 2024Article
- Genome-Wide Analysis of p53 Targets Reveals SCN2A as a Novel Player in p53-Induced Cell Arrest in HPV-Positive Cells.Viruses · 2024Article
- Exploring the genetic and molecular basis of differences in multiple myeloma of individuals of African and European descent.Cell death and differentiation · 2024Review
- Review
- Emerging insights into ethnic-specific TP53 germline variants.Journal of the National Cancer Institute · 2023Review
- Gene signatures associated with prognosis and chemotherapy resistance in glioblastoma treated with temozolomide.Frontiers in genetics · 2023Article
- Elucidating the chain of command: our current understanding of critical target genes for p53-mediated tumor suppression.Critical reviews in biochemistry and molecular biologyReview
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Authors and funding
27 authors at 6 institutions in 1 country.
Funding
Abstract
TP53 is the most frequently mutated gene in cancer, yet key target genes for p53-mediated tumor suppression remain unidentified. Here, we characterize a rare, African-specific germline variant of TP53 in the DNA-binding domain Tyr107His (Y107H). Nuclear magnetic resonance and crystal structures reveal that Y107H is structurally similar to wild-type p53. Consistent with this, we find that Y107H can suppress tumor colony formation and is impaired for the transactivation of only a small subset of p53 target genes; this includes the epigenetic modifier PADI4, which deiminates arginine to the nonnatural amino acid citrulline. Surprisingly, we show that Y107H mice develop spontaneous cancers and metastases and that Y107H shows impaired tumor suppression in two other models. We show that PADI4 is itself tumor suppressive and that it requires an intact immune system for tumor suppression. We identify a p53-PADI4 gene signature that is predictive of survival and the efficacy of immune-checkpoint inhibitors. SIGNIFICANCE: We analyze the African-centric Y107H hypomorphic variant and show that it confers increased cancer risk; we use Y107H in order to identify PADI4 as a key tumor-suppressive p53 target gene that contributes to an immune modulation signature and that is predictive of cancer survival and the success of immunotherapy. See related commentary by Bhatta and Cooks, p. 1518. This article is highlighted in the In This Issue feature, p. 1501.
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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.