ArticleChemical research in toxicology2016
Covalent Modification of CDK2 by 4-Hydroxynonenal as a Mechanism of Inhibition of Cell Cycle Progression.
Article in Chemical research in toxicology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
13 citing papers in PubMed, 20 citations in OpenAlex.
- Targeting cyclin-dependent kinase 2 (CDK2) interactions with cyclins and Speedy 1 (Spy1) for cancer and male contraception.Future medicinal chemistry · 2025Review
- Review
- The 4-Hydroxynonenal-Protein Adducts and Their Biological Relevance: Are Some Proteins Preferred Targets?Antioxidants (Basel, Switzerland) · 2023Review
- Methylglyoxal and Its Adducts: Induction, Repair, and Association with Disease.Chemical research in toxicology · 2022Review
- The Potential Role of Mitochondrial Acetaldehyde Dehydrogenase 2 in Urological Cancers From the Perspective of Ferroptosis and Cellular Senescence.Frontiers in cell and developmental biology · 2022Review
- Lipid-derived electrophiles mediate the effects of chemotherapeutic topoisomerase I poisons.Cell chemical biology · 2021Article
- Functionalized Scout Fragments for Site-Specific Covalent Ligand Discovery and Optimization.ACS central science · 2021Article
- ABHD11 maintains 2-oxoglutarate metabolism by preserving functional lipoylation of the 2-oxoglutarate dehydrogenase complex.Nature communications · 2020Article
- 4-Hydroxynonenal and 4-Oxononenal Differentially Bind to the Redox Sensor MitoNEET.Chemical research in toxicology · 2019Article
- Signaling by 4-hydroxy-2-nonenal: Exposure protocols, target selectivity and degradation.Archives of biochemistry and biophysics · 2017Review
- Electrophilic Modification of PKM2 by 4-Hydroxynonenal and 4-Oxononenal Results in Protein Cross-Linking and Kinase Inhibition.Chemical research in toxicology · 2017Article
- 4-Hydroxy-2-nonenal: a critical target in oxidative stress?American journal of physiology. Cell physiology · 2016Review
- Artemisinin and its derivatives can significantly inhibit lung tumorigenesis and tumor metastasis through Wnt/β-catenin signaling.Oncotarget · 2016Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Oxidative stress is a contributing factor in a number of chronic diseases, including cancer, atherosclerosis, and neurodegenerative diseases. Lipid peroxidation that occurs during periods of oxidative stress results in the formation of lipid electrophiles, which can modify a multitude of proteins in the cell. 4-Hydroxy-2-nonenal (HNE) is one of the most well-studied lipid electrophiles and has previously been shown to arrest cells at the G1/S transition. Recently, proteomic data have shown that HNE is capable of covalently modifying CDK2, the kinase responsible for the G1/S transition. Here, we identify the sites adducted by HNE using recombinant CDK2 and show that HNE treatment suppresses the kinase activity of the enzyme. We further identify sites of adduction in HNE-treated intact human colorectal carcinoma cells (RKO) and show that HNE-dependent modification in cells is long-lived, disrupts CDK2 function, and correlates with a delay of progression of the cells into S-phase. We propose that adduction of CDK2 by HNE directly alters its activity, contributing to the cell cycle delay.
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.