ArticleCell death & disease2015
The conserved Trp114 residue of thioredoxin reductase 1 has a redox sensor-like function triggering oligomerization and crosslinking upon oxidative stress related to cell death.
Article in Cell death & disease, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 46 citations in OpenAlex.
- Selenoprotein thioredoxin reductase 1 promotes cancer cells ferroptosis by suppressing GPX4 expression.Cell death and differentiation · 2026Article
- Intracellular enzymatic reducing systems control receptor tyrosine kinase signaling via PTP1B.Science advances · 2026Article
- Pharmacological Inhibition of TXNRD1 by a Small Molecule Flavonoid Butein Overcomes Cisplatin Resistance in Lung Cancer Cells.Biological trace element research · 2025Article
- Comparative effects of selenium-enriched lactobacilli and selenium-enriched yeast on performance, egg selenium enrichment, antioxidant capacity, and ileal microbiota in laying hens.Journal of animal science and biotechnology · 2025Article
- The C-terminal selenenylsulfide of extracellular/non-reduced thioredoxin reductase endows this protein with selectivity to small-molecule electrophilic reagents under oxidative conditions.Frontiers in molecular biosciences · 2024Article
- Benzophenanthridine Alkaloid Chelerythrine Elicits Necroptosis of Gastric Cancer Cells via Selective Conjugation at the Redox Hyperreactive C-Terminal SecMolecules (Basel, Switzerland) · 2023Article
- Anti-Inflammatory Effect of Dimethyl Fumarate Associates with the Inhibition of Thioredoxin Reductase 1 in RAW 264.7 Cells.Molecules (Basel, Switzerland) · 2022Article
- Analyzing the postulated inhibitory effect of Manumycin A on farnesyltransferase.Frontiers in chemistry · 2022Article
- Chlorophyllin Inhibits Mammalian Thioredoxin Reductase 1 and Triggers Cancer Cell Death.Antioxidants (Basel, Switzerland) · 2021Article
- Qualitative Differences in Protection of PTP1B Activity by the Reductive Trx1 or TRP14 Enzyme Systems upon Oxidative Challenges with Polysulfides or HAntioxidants (Basel, Switzerland) · 2021Article
- Molecular Basis for the Interactions of Human Thioredoxins with Their Respective Reductases.Oxidative medicine and cellular longevity · 2021Article
- Acetylated Thioredoxin Reductase 1 Resists Oxidative Inactivation.Frontiers in chemistry · 2021Article
- Identification and targeting of selective vulnerability rendered by tamoxifen resistance.Breast cancer research : BCR · 2020Article
- Control of protein function through oxidation and reduction of persulfidated states.Science advances · 2020Article
- Inhibition and crosslinking of the selenoprotein thioredoxin reductase-1 by p-benzoquinone.Redox biology · 2020Article
- Bicarbonate is essential for protein-tyrosine phosphatase 1B (PTP1B) oxidation and cellular signaling through EGF-triggered phosphorylation cascades.The Journal of biological chemistry · 2019Article
- Acetylation Regulates Thioredoxin Reductase Oligomerization and Activity.Antioxidants & redox signaling · 2018Article
- The A to Z of modulated cell patterning by mammalian thioredoxin reductases.Free radical biology & medicine · 2018Review
- Thioredoxin reductase 1 and NADPH directly protect protein tyrosine phosphatase 1B from inactivation during HThe Journal of biological chemistry · 2017Article
- Predicting the Cytotoxic Potency of Cigarette Smoke by Assessing the Thioredoxin Reductase Inhibitory Capacity of Cigarette Smoke Extract.International journal of environmental research and public health · 2016Article
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Authors and funding
14 authors at 4 institutions in 3 countries.
Funding
Abstract
The selenoprotein thioredoxin reductase 1 (TrxR1) has several key roles in cellular redox systems and reductive pathways. Here we discovered that an evolutionarily conserved and surface-exposed tryptophan residue of the enzyme (Trp114) is excessively reactive to oxidation and exerts regulatory functions. The results indicate that it serves as an electron relay communicating with the FAD moiety of the enzyme, and, when oxidized, it facilitates oligomerization of TrxR1 into tetramers and higher multimers of dimers. A covalent link can also be formed between two oxidized Trp114 residues of two subunits from two separate TrxR1 dimers, as found both in cell extracts and in a crystal structure of tetrameric TrxR1. Formation of covalently linked TrxR1 subunits became exaggerated in cells on treatment with the pro-oxidant p53-reactivating anticancer compound RITA, in direct correlation with triggering of a cell death that could be prevented by antioxidant treatment. These results collectively suggest that Trp114 of TrxR1 serves a function reminiscent of an irreversible sensor for excessive oxidation, thereby presenting a previously unrecognized level of regulation of TrxR1 function in relation to cellular redox state and cell death induction.
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