ArticleThe Journal of biological chemistry2019
p53 reactivation with induction of massive apoptosis-1 (PRIMA-1) inhibits amyloid aggregation of mutant p53 in cancer cells.
Article in The Journal of biological chemistry, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers, 1 of them a synthesis that pooled it.
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Who cites it
49 citing papers in PubMed, 1 synthesis or guideline pooled it.
- The proteasome as a druggable target with multiple therapeutic potentialities: Cutting and non-cutting edges.Pharmacology & therapeutics · 2020Pooled it
- Multi-Site Aggregation of p53: Insights from Self- and Co-Aggregation of Multiple Aggregation-Prone Regions.ACS omega · 2026Article
- Cancer-linked aggregation of p53 is driven by sequence-encoded frustration, solvation, and hydrophobic gating absent in its paralogs.Communications chemistry · 2026Article
- Restoration of the Y220C p53 Full-Length Mutant by PK11000: a Molecular Dynamics Study of an Intrinsically Disordered Protein.ACS omega · 2026Article
- Molecular targets and therapies associated with poor prognosis of triple‑negative breast cancer (Review).International journal of oncology · 2025Review
- Designed Cell-Penetrating Peptide Constructs for Inhibition of Pathogenic Protein Self-Assembly.Pharmaceutics · 2024Review
- Oncogenic p53 triggers amyloid aggregation of p63 and p73 liquid droplets.Communications chemistry · 2024Article
- Impacts of cytoplasmic p53 aggregates on the prognosis and the transcriptome in lung squamous cell carcinoma.Cancer science · 2024Article
- Review
- Molecular Complexity of Colorectal Cancer: Pathways, Biomarkers, and Therapeutic Strategies.Cancer management and research · 2024Review
- Phase separations in oncogenesis, tumor progressions and metastasis: a glance from hallmarks of cancer.Journal of hematology & oncology · 2023Review
- A Review of Childhood Acute Myeloid Leukemia: Diagnosis and Novel Treatment.Pharmaceuticals (Basel, Switzerland) · 2023Review
- The p53 reactivator PRIMA-1Investigational new drugs · 2023Article
- Amyloid-like p53 as prognostic biomarker in serous ovarian cancer-a study of the OVCAD consortium.Oncogene · 2023Article
- Review
- Anti-inflammatory effects of PRIMA-1Inflammopharmacology · 2023Article
- The Challenges and Prospects of p53-Based Therapies in Ovarian Cancer.Biomolecules · 2023Review
- Review
- Targeting p53 misfolding conundrum by stabilizing agents and their analogs in breast cancer therapy: a comprehensive computational analysis.Frontiers in pharmacology · 2023Article
- Liquid‒liquid phase separation: roles and implications in future cancer treatment.International journal of biological sciences · 2023Review
Corrections and comments
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Authors and funding
7 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
p53 mutants can form amyloid-like structures that accumulate in cells. p53 reactivation with induction of massive apoptosis-1 (PRIMA-1) and its primary active metabolite, 2-methylene-3-quinuclidinone (MQ), can restore unfolded p53 mutants to a native conformation that induces apoptosis and activates several p53 target genes. However, whether PRIMA-1 can clear p53 aggregates is unclear. In this study, we investigated whether PRIMA-1 can restore aggregated mutant p53 to a native form. We observed that the p53 mutant protein is more sensitive to both PRIMA-1 and MQ aggregation inhibition than WT p53. The results of anti-amyloid oligomer antibody assays revealed that PRIMA-1 reverses mutant p53 aggregate accumulation in cancer cells. Size-exclusion chromatography of the lysates from mutant p53-containing breast cancer and ovarian cell lines confirmed that PRIMA-1 substantially decreases p53 aggregates. We also show that MDA-MB-231 cell lysates can "seed" aggregation of the central core domain of recombinant WT p53, corroborating the prion-like behavior of mutant p53. We also noted that this aggregation effect was inhibited by MQ and PRIMA-1. This study provides the first demonstration that PRIMA-1 can rescue amyloid-state p53 mutants, a strategy that could be further explored as a cancer treatment.
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