ArticlePloS one2014
Arsenic trioxide reactivates proteasome-dependent degradation of mutant p53 protein in cancer cells in part via enhanced expression of Pirh2 E3 ligase.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 35 papers.
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.
Decitabine and Arsenic Trioxide(ATO) in the Treatment of Myelodysplasic Syndrome
Decitabine,Cytarabine(Ara-C) and Arsenic Trioxide(ATO) in the Treatment of Acute Myeloid Leukemia With p53 Mutations
Who cites it
35 citing papers in PubMed, 49 citations in OpenAlex.
- p53 in colorectal cancer: from a master player to a privileged therapy target.Journal of translational medicine · 2025Review
- The Role of P53 in Immune Evasion and Therapeutic Strategies in Hematologic Malignancies.Journal of Cancer · 2025Review
- Inorganic arsenic modulates cell apoptosis by regulating Argonaute 2 expression via the p53 pathway.Toxicology research · 2025Article
- TP53-mutated acute myeloid leukemia and myelodysplastic syndrome: biology, treatment challenges, and upcoming approaches.Annals of hematology · 2024Review
- Translating p53-based therapies for cancer into the clinic.Nature reviews. Cancer · 2024Review
- Inhibition of mitochondrial translocase SLC25A5 and histone deacetylation is an effective combination therapy in neuroblastoma.International journal of cancer · 2023Article
- Review
- Review
- Targeting mutant p53 stabilization for cancer therapy.Frontiers in pharmacology · 2023Review
- GOF Mutant p53 in Cancers: A Therapeutic Challenge.Cancers · 2022Review
- The Role of E3 Ligase Pirh2 in Disease.Cells · 2022Review
- Targeting Post-Translational Regulation of p53 in Colorectal Cancer by Exploiting Vulnerabilities in the p53-MDM2 Axis.Cancers · 2022Review
- TargetingOncoTargets and therapy · 2022Review
- Arsenic co-carcinogenesis: Inhibition of DNA repair and interaction with zinc finger proteins.Seminars in cancer biology · 2021Review
- Review
- The RNA-binding protein HuR is a novel target of Pirh2 E3 ubiquitin ligase.Cell death & disease · 2021Article
- Regulation of p53 by E3s.Cancers · 2021Review
- Gain-of-function mutant p53 in cancer progression and therapy.Journal of molecular cell biology · 2020Review
- Cutting Edge Molecular Therapy for Acute Myeloid Leukemia.International journal of molecular sciences · 2020Review
- Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
The p53 gene is mutated in more than 50% of human tumors. Mutant p53 exerts an oncogenic function and is often highly expressed in cancer cells due to evasion of proteasome-dependent degradation. Thus, reactivating proteasome-dependent degradation of mutant p53 protein is an attractive strategy for cancer management. Previously, we found that arsenic trioxide (ATO), a drug for acute promyelocytic leukemia, degrades mutant p53 protein through a proteasome pathway. However, it remains unclear what is the E3 ligase that targets mutant p53 for degradation. In current study, we sought to identify an E3 ligase necessary for ATO-mediated degradation of mutant p53. We found that ATO induces expression of Pirh2 E3 ligase at the transcriptional level. We also found that knockdown of Pirh2 inhibits, whereas ectopic expression of Pirh2 enhances, ATO-induced degradation of mutant p53 protein. Furthermore, we found that Pirh2 E3 ligase physically interacts with and targets mutant p53 for polyubiquitination and subsequently proteasomal degradation. Interestingly, we found that ATO cooperates with HSP90 or HDAC inhibitor to promote mutant p53 degradation and growth suppression in tumor cells. Together, these data suggest that ATO promotes mutant p53 degradation in part via induction of the Pirh2-dependent proteasome pathway.
Indexed as
Identifiers
What OpenQuestion holds
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.