ArticleJournal of the American Society for Mass Spectrometry2011
Identification of two reactive cysteine residues in the tumor suppressor protein p53 using top-down FTICR mass spectrometry.
Article in Journal of the American Society for Mass Spectrometry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 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.
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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
26 citing papers in PubMed, 52 citations in OpenAlex.
- Deciphering the safeguarding role of cysteine residues in p53 against HCommunications chemistry · 2025Article
- Covalent Fragments Acting as Tyrosine Mimics for Mutant p53-Y220C Rescue by Nucleophilic Aromatic Substitution.ACS pharmacology & translational science · 2024Article
- Covalent Modification of p53 by (ACS pharmacology & translational science · 2024Article
- Evaluation of a Covalent Library of Diverse Warheads (CovLib) Binding to JNK3, USP7, or p53.Drug design, development and therapy · 2024Article
- Review
- Nitrogen Mustard Alkylates and Cross-Links p53 in Human Keratinocytes.Chemical research in toxicology · 2022Article
- Structural basis of reactivation of oncogenic p53 mutants by a small molecule: methylene quinuclidinone (MQ).Nature communications · 2021Article
- Redox Sensitive Cysteine Residues as Crucial Regulators of Wild-Type and Mutant p53 Isoforms.Cells · 2021Review
- An Integrated Mass Spectrometry and Molecular Dynamics Simulations Approach Reveals the Spatial Organization Impact of Metal-Binding Sites on the Stability of Metal-Depleted Metallothionein-2 Species.Journal of the American Chemical Society · 2021Article
- p53 Forms Redox-Dependent Protein-Protein Interactions through Cysteine 277.Antioxidants (Basel, Switzerland) · 2021Article
- Oxidative stress in obesity-associated hepatocellular carcinoma: sources, signaling and therapeutic challenges.Oncogene · 2021Review
- Mass Spectrometry-Based Structural Analysis of Cysteine-Rich Metal-Binding Sites in Proteins with MetaOdysseus R Software.Journal of proteome research · 2021Article
- Metal- and Affinity-Specific Dual Labeling of Cysteine-Rich Proteins for Identification of Metal-Binding Sites.Analytical chemistry · 2020Article
- Article
- p53 as a hub in cellular redox regulation and therapeutic target in cancer.Journal of molecular cell biology · 2019Review
- Mass Spectrometry in Advancement of Redox Precision Medicine.Advances in experimental medicine and biology · 2019Review
- APR-246 reactivates mutant p53 by targeting cysteines 124 and 277.Cell death & disease · 2018Article
- Mitochondrial Thioredoxin System as a Modulator of Cyclophilin D Redox State.Scientific reports · 2016Article
- Peroxiredoxins and the Regulation of Cell Death.Molecules and cells · 2016Review
- KEAP1-NRF2 signalling and autophagy in protection against oxidative and reductive proteotoxicity.The Biochemical journal · 2015Review
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The tumor suppressor p53 is a redox-regulated transcription factor involved in cell cycle arrest, apoptosis and senescence in response to multiple forms of stress, as well as many other cellular processes such as DNA repair, glycolysis, autophagy, oxidative stress and differentiation. The discovery of cysteine-targeting compounds that cause re-activation of mutant p53 and the death of tumor cells in vivo has emphasized the functional importance of p53 thiols. Using a combination of top-down and middle-down FTICR mass spectrometry, we show that of the 10 Cys residues in the core domain of wild-type p53, Cys182 and Cys277 exhibit a remarkable preference for modification by the alkylating reagent N-ethylmaleimide. The assignment of Cys182 and Cys277 as the two reactive Cys residues was confirmed by site-directed mutagenesis. Further alkylation of p53 beyond Cys182 and Cys277 was found to trigger co-operative modification of the remaining seven Cys residues and protein unfolding. This study highlights the power of top-down FTICR mass spectrometry for analysis of the cysteine reactivity and redox chemistry in multiple cysteine-containing proteins.
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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.