ArticleCell death & disease2017
ROS-induced cleavage of NHLRC2 by caspase-8 leads to apoptotic cell death in the HCT116 human colon cancer cell line.
Article in Cell death & disease, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 59 citations in OpenAlex.
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- Pyra-metho-carnil disrupts cancer cell proteostasis and induces apoptosis by binding to KDEL receptors.Scientific reports · 2026Article
- Green tea-derived exosome-like nanoparticles attenuate oxidative stress-induced skin senescence via modulation of p38 MAPK signaling.Frontiers in pharmacology · 2026Article
- The TaNHLP1-TaRACK1A module regulates tillering via abscisic acid signaling in wheat.Nature communications · 2025Article
- Altered behaviour and immune response in mice with NHLRC2 p.Asp148Tyr variant.Brain, behavior, & immunity - health · 2025Article
- The Arg/N-degron pathway mediates the secretion of apoptotic exosomes under oxidative stress in cancer cell.iScience · 2025Article
- RAD52-mediated repair of DNA double-stranded breaks at inactive centromeres leads to subsequent apoptotic cell death.Nucleic acids research · 2024Article
- Case Report: Clinical manifestations and treatment of two Chinese patients with FINCA syndrome carrying a novel variant ofFrontiers in pediatrics · 2024Article
- Widespread 8-oxoguanine modifications of miRNA seeds differentially regulate redox-dependent cancer development.Nature cell biology · 2023Article
- Broadening the phenotypic and molecular spectrum of FINCA syndrome: Biallelic NHLRC2 variants in 15 novel individuals.European journal of human genetics : EJHG · 2023Article
- High NHLRC2 expression is associated with shortened survival in lung adenocarcinoma.Translational lung cancer research · 2023Article
- Streamlined Efficient Synthesis and Antioxidant Activity of γ-[Glutamyl]Molecules (Basel, Switzerland) · 2023Article
- Application of CRISPR-Cas9 gene editing technology in basic research, diagnosis and treatment of colon cancer.Frontiers in endocrinology · 2023Review
- Novel patients with NHLRC2 variants expand the phenotypic spectrum of FINCA disease.Frontiers in neuroscience · 2023Article
- Construction and Validation of a Protein-associated Prognostic Model for Gastrointestinal Cancer.Combinatorial chemistry & high throughput screening · 2023Article
- Inhibition of insulin-like growth factor-1 receptor enhances eribulin-induced DNA damage in colorectal cancer.Cancer science · 2022Article
- 3D cell cultures, as a surrogate for animal models, enhance the diagnostic value of preclinical in vitro investigations by adding information on the tumour microenvironment: a comparative study of new dual-mode HDAC inhibitors.Investigational new drugs · 2022Article
- NHLRC2 expression is increased in idiopathic pulmonary fibrosis.Respiratory research · 2022Article
- Structure of Arabidopsis SOQ1 lumenal region unveils C-terminal domain essential for negative regulation of photoprotective qH.Nature plants · 2022Article
- FINCA syndrome-Defining neurobehavioral phenotype in survivors into late childhood.Molecular genetics & genomic medicine · 2022Article
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
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Abstract
Excess production of reactive oxygen species (ROS) is known to cause apoptotic cell death. However, the molecular mechanisms whereby ROS induce apoptosis remain elusive. Here we show that the NHL-repeat-containing protein 2 (NHLRC2) thioredoxin-like domain protein is cleaved by caspase-8 in ROS-induced apoptosis in the HCT116 human colon cancer cell line. Treatment of HCT116 cells with the oxidant tert-butyl hydroperoxide (tBHP) induced apoptosis and reduced NHLRC2 protein levels, whereas pretreatment with the antioxidant N-acetyl-L-cysteine prevented apoptosis and the decrease in NHLRC2 protein levels seen in tBHP-treated cells. Furthermore, the ROS-induced decrease in NHLRC2 protein levels was relieved by the caspase inhibitor z-VAD-fmk. We found that the thioredoxin-like domain of NHLRC2 interacted with a proenzyme form of caspase-8, and that caspase-8 cleaved NHLRC2 protein at Asp580 in vitro. Furthermore, siRNA-mediated knockdown of caspase-8 blocked the ROS-induced decrease in NHLRC2 protein levels. Both shRNA and CRISPR-Cas9-mediated loss of NHLRC2 resulted in an increased susceptibility of HCT116 cells to ROS-induced apoptosis. These results suggest that excess ROS production causes a caspase-8-mediated decrease in NHLRC2 protein levels, leading to apoptotic cell death in colon cancer cells, and indicate an important role of NHLRC2 in the regulation of ROS-induced apoptosis.
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