ArticleOncogene2003
Proteolytic regulation of Forkhead transcription factor FOXO3a by caspase-3-like proteases.
Article in Oncogene, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 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
40 citing papers in PubMed, 73 citations in OpenAlex.
- Chasing the FoxO in Metabolic Disorders: Novel Considerations for Oxidative Stress, Programmed Cell Death, Wnt, and the Gut Microbiome.Antioxidants (Basel, Switzerland) · 2026Review
- Cognitive Impairment in Multiple Sclerosis.Bioengineering (Basel, Switzerland) · 2023Review
- The forkhead box O3 (FOXO3): a key player in the regulation of ischemia and reperfusion injury.Cellular and molecular life sciences : CMLS · 2023Review
- Innovative therapeutic strategies for cardiovascular disease.EXCLI journal · 2023Review
- GDF-5 promotes epidermal stem cells proliferation via Foxg1-cyclin D1 signaling.Stem cell research & therapy · 2021Article
- Protective Effect of Biobran/MGN-3 against Sporadic Alzheimer's Disease Mouse Model: Possible Role of Oxidative Stress and Apoptotic Pathways.Oxidative medicine and cellular longevity · 2021Article
- Nicotinamide as a Foundation for Treating Neurodegenerative Disease and Metabolic Disorders.Current neurovascular research · 2021Review
- cIAP2 Is an Independent Signaling and Survival Factor during Mammary Lactational Involution and Tumorigenesis.Journal of mammary gland biology and neoplasia · 2018Article
- Foxo3 Transcription Factor Drives Pathogenic T Helper 1 Differentiation by Inducing the Expression of Eomes.Immunity · 2016Article
- Interactions between mitochondria and the transcription factor myocyte enhancer factor 2 (MEF2) regulate neuronal structural and functional plasticity and metaplasticity.The Journal of physiology · 2015Review
- FoxO proteins in the nervous system.Analytical cellular pathology (Amsterdam) · 2015Review
- HTLV-1 Tax-mediated inhibition of FOXO3a activity is critical for the persistence of terminally differentiated CD4+ T cells.PLoS pathogens · 2014Article
- Cleavage of the JunB transcription factor by caspases generates a carboxyl-terminal fragment that inhibits activator protein-1 transcriptional activity.The Journal of biological chemistry · 2013Article
- Caspases cleave and inhibit the microRNA processing protein DiGeorge Critical Region 8.Protein science : a publication of the Protein Society · 2012Article
- NAMPT overexpression in prostate cancer and its contribution to tumor cell survival and stress response.Oncogene · 2011Article
- Novel avenues of drug discovery and biomarkers for diabetes mellitus.Journal of clinical pharmacology · 2011Review
- Upregulation of Id1 by Epstein-Barr virus-encoded LMP1 confers resistance to TGFbeta-mediated growth inhibition.Molecular cancer · 2010Article
- FOXO3a governs early and late apoptotic endothelial programs during elevated glucose through mitochondrial and caspase signaling.Molecular and cellular endocrinology · 2010Article
- Early apoptotic vascular signaling is determined by Sirt1 through nuclear shuttling, forkhead trafficking, bad, and mitochondrial caspase activation.Current neurovascular research · 2010Article
- Regulation of the intracellular localization of Foxo3a by stress-activated protein kinase signaling pathways in skeletal muscle cells.Molecular and cellular biology · 2010Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Forkhead family transcription factors are critical regulators of cell cycle progression and apoptosis in hematopoietic cells. Here, we show that FOXO3a (also known as FKHRL1) is a new substrate of caspase-3-like proteases during apoptosis in T lymphocytes. FOXO3a was cleaved in vivo by caspases in leukemic Jurkat cells following engagement of Fas (CD95) receptor, staurosporine, and etoposide treatment, but not following engagement of CD99, a caspase-independent cell death inducer. Caspase-mediated cleavage of FOXO3a was also observed in CD4+ peripheral T cells subjected to activation-induced cell death. The expression of the death adapter FADD and caspase-8 was required for Fas-induced FOXO3a cleavage, but activation of survival pathways by overexpression of FLICE-inhibitory protein or phorbol myristate acetate treatment prevented it. FOXO3a was cleaved in vitro by caspase-3-like proteases at the consensus sequence DELD304A, releasing the N-terminal DNA-binding domain of FOXO3a from its C-terminal transactivating domain. Whereas full-length FOXO3a enhanced Forkhead response element-dependent transcription and apoptosis in Jurkat cells, both fragments were inactive to promote gene activation and cell death. In contrast, a caspase-resistant FOXO3a mutant exhibited enhanced transcriptional and proapoptotic activities. Together, these results indicate that the proteolytic cleavage of FOXO3a by caspases may represent a novel regulatory mechanism of FOXO3a activity during death receptors signaling.
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.