ArticleThe American journal of pathology2002
Caspase-3-Dependent Cleavage of the Glutamate-L-Cysteine Ligase Catalytic Subunit during Apoptotic Cell Death.
Article in The American journal of pathology, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 1 of them a synthesis that pooled it.
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
37 citing papers in PubMed, 1 synthesis or guideline pooled it, 77 citations in OpenAlex.
- Pooled it
- Enzymatic/Mitochondrial Import Bottleneck in Sepsis with Possible Extensions to DIC: IV Glutathione and Hinokitiol as Potential Therapeutic Candidates.International journal of molecular sciences · 2026Article
- Selenoproteins: Minute yet vital players governing cellular fate.Genes & diseases · 2026Review
- Lens aging and disease: Molecular mechanisms, functional consequences, and pharmacological implications.Progress in retinal and eye research · 2026Review
- PARP-1 prevents osteoarthritis pathogenesis by inhibiting apoptosis in chondrocytes: an animal study.Arthritis research & therapy · 2026Article
- Prevention of age-related truncation of γ-glutamylcysteine ligase catalytic subunit (GCLC) delays cataract formation.Science advances · 2024Article
- Nrf2/ARE axis signalling in hepatocyte cellular death.Molecular biology reports · 2022Review
- Lipoperoxide Nanoemulsion as Adjuvant in Cisplatin Cancer Therapy: In Vitro Study on Human Colon Adenocarcinoma DLD-1 Cells.Nanomaterials (Basel, Switzerland) · 2021Article
- Aging lens epithelium is susceptible to ferroptosis.Free radical biology & medicine · 2021Article
- The protective role of glutathione in osteoarthritis.Journal of clinical orthopaedics and trauma · 2021Review
- Down regulation of glutathione and glutamate cysteine ligase in the inflammatory response of macrophages.Free radical biology & medicine · 2020Article
- γ-Glutamyltransferase enzyme activity of cancer cells modulates L-γ-glutamyl-p-nitroanilide (GPNA) cytotoxicity.Scientific reports · 2019Article
- Changes in Oxidant Defense, Apoptosis, and Cognitive Abilities During Treatment for Childhood Leukemia.Biological research for nursing · 2018Article
- Sex-specific molecular genetic response to UVB exposure in Xiphophorus maculatus skin.Comparative biochemistry and physiology. Toxicology & pharmacology : CBP · 2015Article
- Targeting the Achilles heel of multidrug-resistant cancer by exploiting the fitness cost of resistance.Chemical reviews · 2014Review
- Emerging regulatory paradigms in glutathione metabolism.Advances in cancer research · 2014Review
- Glutathione synthesis.Biochimica et biophysica acta · 2013Review
- Decreased zinc availability affects glutathione metabolism in neuronal cells and in the developing brain.Toxicological sciences : an official journal of the Society of Toxicology · 2013Article
- Low-level domoic acid protects mouse cerebellar granule neurons from acute neurotoxicity: role of glutathione.Toxicological sciences : an official journal of the Society of Toxicology · 2013Article
- Glutathione efflux and cell death.Antioxidants & redox signaling · 2012Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Apoptotic cell death is usually accompanied by activation of a family of cysteine proteases termed caspases. Caspases mediate the selective proteolysis of multiple cellular targets often resulting in the disruption of survival pathways. Intracellular levels of the antioxidant glutathione (GSH) are an important determinant of cellular susceptibility to apoptosis. The rate-limiting step in GSH biosynthesis is mediated by glutamate-L-cysteine ligase (GCL), a heterodimeric enzyme consisting of a catalytic (GCLC) and a modifier (GCLM) subunit. In this report we demonstrate that GCLC is a direct target for caspase-mediated cleavage in multiple models of apoptotic cell death. Mutational analysis revealed that caspase-mediated cleavage of GCLC occurs at Asp(499) within the sequence AVVD(499)G. GCLC cleavage occurs upstream of Cys(553), which is thought to be important for association with GCLM. GCLC cleavage is accompanied by a rapid loss of intracellular GSH due to caspase-mediated extrusion of GSH from the cell. However, while GCLC cleavage is dependent on caspase-3, GSH extrusion occurs by a caspase-3-independent mechanism. Our identification of GCLC as a target for caspase-3-dependent cleavage during apoptotic cell death suggests that this post-translational modification may represent a novel mechanism for regulating GSH biosynthesis during apoptosis.
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.