ArticleOncogene2010
15-Deoxy-Delta(12,14)-prostaglandin J(2) stabilizes, but functionally inactivates p53 by binding to the cysteine 277 residue.
Article in Oncogene, 2010. 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, 34 citations in OpenAlex.
- Cysteine-based molecular switches: a focus on KEAP1 and BACH1 in regulating the antioxidant response.Archives of toxicology · 2026Review
- Covalent Fragments Acting as Tyrosine Mimics for Mutant p53-Y220C Rescue by Nucleophilic Aromatic Substitution.ACS pharmacology & translational science · 2024Article
- Short Survey on the Protein Modifications in Plasma during SARS-CoV-2 Infection.International journal of molecular sciences · 2023Article
- Nitrogen Mustard Alkylates and Cross-Links p53 in Human Keratinocytes.Chemical research in toxicology · 2022Article
- JNK-mediated Ser27 phosphorylation and stabilization of SIRT1 promote growth and progression of colon cancer through deacetylation-dependent activation of Snail.Molecular oncology · 2022Article
- STAT3 as a Potential Target for Tumor Suppressive Effects of 15-Deoxy-ΔJournal of cancer prevention · 2021Article
- 15-Deoxy-ΔCells · 2021Article
- Protein Lipoxidation: Basic Concepts and Emerging Roles.Antioxidants (Basel, Switzerland) · 2021Review
- 15d-PGJ2 is a new hope for controlling tumor growth.American journal of translational research · 2018Review
- Autocrine secretion of 15d-PGJ2 mediates simvastatin-induced apoptotic burst in human metastatic melanoma cells.British journal of pharmacology · 2014Article
- Electrophilic lipid mediator 15-deoxy-Δ12,14-prostaglandin j2 modifies glucocorticoid signaling via receptor SUMOylation.Molecular and cellular biology · 2014Article
- Prostaglandin 15d-PGJ(2) inhibits androgen receptor signaling in prostate cancer cells.Molecular endocrinology (Baltimore, Md.) · 2013Article
- Targeting of histone acetyltransferase p300 by cyclopentenone prostaglandin Δ(12)-PGJ(2) through covalent binding to Cys(1438).Chemical research in toxicology · 2012Article
- Article
- Proteomic profiling of acrolein adducts in human lung epithelial cells.Journal of proteomics · 2011Article
- Identification of two reactive cysteine residues in the tumor suppressor protein p53 using top-down FTICR mass spectrometry.Journal of the American Society for Mass Spectrometry · 2011Article
- Article
- Stabilization of mutant p53 via alkylation of cysteines and effects on DNA binding.Protein science : a publication of the Protein Society · 2010Article
Corrections and comments
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Authors and funding
5 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
15-Deoxy-Delta(12,14)-prostaglandin J(2) (15d-PGJ(2)), a representative cyclopentenone prostaglandin, has many interesting biological effects. In this study, treatment of human breast cancer cells (MCF-7) with 15d-PGJ(2) led to accumulation of p53 protein. However, the p53 DNA binding and its transcriptional activity were significantly reduced. 15d-PGJ(2) directly modified p53 as verified by reacting recombinant p53 with biotinylated 15d-PGJ(2). 9,10-Dihydro-15-deoxy-Delta(12,14)-prostaglandin J(2) lacking the electrophilic alpha,beta-unsaturated functionality failed to inhibit p53 DNA binding as well as to modify p53. Moreover, by conducting an in vitro [(35)S]-labeled p53 translation assay, we identified cysteine 277 as a putative site of p53 modification by 15d-PGJ(2). The DNA-binding ability of a mutant p53 in which cysteine 277 was substituted by alanine was virtually unaffected by 15d-PGJ(2). Likewise, p53 binding activity of biotinylated 15d-PGJ(2) was abolished in mutant cells. In addition, cells expressing wild-type p53 exhibited p53 protein stability to a greater extent than mutant C277A cells. In conclusion, 15d-PGJ(2) can undergo nucleophilic addition to p53, presumably at the cysteine 277 residue, rendering this tumor suppressor less susceptible to proteasomal degradation.
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Registered trials
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