ArticleProceedings of the National Academy of Sciences of the United States of America2019
iASPP mediates p53 selectivity through a modular mechanism fine-tuning DNA recognition.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 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
20 citing papers in PubMed, 1 synthesis or guideline pooled it, 29 citations in OpenAlex.
- Targeting p53 pathways: mechanisms, structures, and advances in therapy.Signal transduction and targeted therapy · 2023Pooled it
- p53: from understanding its structure to advances in therapeutic targeting.Signal transduction and targeted therapy · 2026Review
- Article
- SREBP1 deficiency aggravates vascular calcification via iASPP-triggered ferroptosis of vascular smooth muscle cells.Cardiovascular diabetology · 2025Article
- PPP1R13L drives cervical cancer progression by suppressing p63-mediated PTEN transcription.Cellular and molecular life sciences : CMLS · 2025Article
- Alternative splicing in the DBD linker region of p63 modulates binding to DNA and iASPP in vitro.Cell death & disease · 2025Article
- Cardiocutaneous syndrome is caused by aggregation of iASPP mutants.Cell death discovery · 2024Article
- Genome-Wide Analysis of p53 Targets Reveals SCN2A as a Novel Player in p53-Induced Cell Arrest in HPV-Positive Cells.Viruses · 2024Article
- Determinants of p53 DNA binding, gene regulation, and cell fate decisions.Cell death and differentiation · 2024Review
- Reconciling ASPP-p53 binding mode discrepancies through an ensemble binding framework that bridges crystallography and NMR data.PLoS computational biology · 2024Article
- Structures of p53/BCL-2 complex suggest a mechanism for p53 to antagonize BCL-2 activity.Nature communications · 2023Article
- p53 inhibitor iASPP is an unexpected suppressor of KRAS and inflammation-driven pancreatic cancer.Cell death and differentiation · 2023Article
- Regulation of immunological tolerance by the p53-inhibitor iASPP.Cell death & disease · 2023Article
- Integrating deep mutational scanning and low-throughput mutagenesis data to predict the impact of amino acid variants.GigaScience · 2022Article
- Designed Ankyrin Repeat Proteins as a tool box for analyzing p63.Cell death and differentiation · 2022Article
- Structural diversity of p63 and p73 isoforms.Cell death and differentiation · 2022Review
- USP1-trapping lesions as a source of DNA replication stress and genomic instability.Nature communications · 2022Article
- Hidden electrostatic energy contributions define dynamic allosteric communications within p53 during molecular recognition.Biophysical journal · 2021Article
- The Role of p53 Signaling in Colorectal Cancer.Cancers · 2021Review
- Tumor suppressor p53: from engaging DNA to target gene regulation.Nucleic acids research · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
16 authors at 4 institutions in 3 countries.
Funding
Abstract
The most frequently mutated protein in human cancer is p53, a transcription factor (TF) that regulates myriad genes instrumental in diverse cellular outcomes including growth arrest and cell death. Cell context-dependent p53 modulation is critical for this life-or-death balance, yet remains incompletely understood. Here we identify sequence signatures enriched in genomic p53-binding sites modulated by the transcription cofactor iASPP. Moreover, our p53-iASPP crystal structure reveals that iASPP displaces the p53 L1 loop-which mediates sequence-specific interactions with the signature-corresponding base-without perturbing other DNA-recognizing modules of the p53 DNA-binding domain. A TF commonly uses multiple structural modules to recognize its cognate DNA, and thus this mechanism of a cofactor fine-tuning TF-DNA interactions through targeting a particular module is likely widespread. Previously, all tumor suppressors and oncoproteins that associate with the p53 DNA-binding domain-except the oncogenic E6 from human papillomaviruses (HPVs)-structurally cluster at the DNA-binding site of p53, complicating drug design. By contrast, iASPP inhibits p53 through a distinct surface overlapping the E6 footprint, opening prospects for p53-targeting precision medicine to improve cancer therapy.
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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.