ArticleThe EMBO journal2003
NF-kappaB protects from the lysosomal pathway of cell death.
Article in The EMBO journal, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 112 citations in OpenAlex.
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- Shedding Light on NF-κB Functions in Cellular Organelles.Frontiers in cell and developmental biology · 2022Review
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- Lysosome Depletion-Triggered Autophagy Impairment in Progressive Kidney Injury.Kidney diseases (Basel, Switzerland) · 2021Review
- Chemical-Genetic Interactions ofMolecules (Basel, Switzerland) · 2021Article
- Novel Approaches of Dysregulating Lysosome Functions in Cancer Cells by Specific Drugs and Its Nanoformulations: A Smart Approach of Modern Therapeutics.International journal of nanomedicine · 2021Review
- The Role of Cysteine Peptidases in Hematopoietic Stem Cell Differentiation and Modulation of Immune System Function.Frontiers in immunology · 2021Review
- Making Connections: p53 and the Cathepsin Proteases as Co-Regulators of Cancer and Apoptosis.Cancers · 2020Review
- Identification of Novel Targets of RBM5 in the Healthy and Injured Brain.Neuroscience · 2020Article
- The molecular machinery of regulated cell death.Cell research · 2019Review
- Antiapoptotic serine protease inhibitors contribute to survival of allergenic TThe Journal of allergy and clinical immunology · 2018Article
- The role of lysosome in cell death regulation.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Review
- Nedd4 E3 ubiquitin ligase promotes cell proliferation and autophagy.Cell proliferation · 2015Article
- Brief report: serpin Spi2A as a novel modulator of hematopoietic progenitor cell formation.Stem cells (Dayton, Ohio) · 2014Article
- Serine protease inhibitor 6 plays a critical role in protecting murine granzyme B-producing regulatory T cells.Journal of immunology (Baltimore, Md. : 1950) · 2013Article
- Erythropoietin-directed erythropoiesis depends on serpin inhibition of erythroblast lysosomal cathepsins.The Journal of experimental medicine · 2013Article
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Authors and funding
14 authors at 1 institution in 1 country.
Funding
Abstract
The programme of gene expression induced by RelA/NF-kappaB transcription factors is critical to the control of cell survival. Ligation of 'death receptors' such as tumor necrosis factor receptor 1 (TNF-R1) triggers apoptosis, as well as NF-kappaB, which counteracts this process by activating the transcription of anti-apoptotic genes. In addition to activating caspases, TNF-R1 stimulation causes the release of cathepsins, most notably cathepsin B, from the lysosome into the cytoplasm where they induce apoptosis. Here we report a mechanism by which NF-kappaB protects cells against TNF-alpha-induced apoptosis: inhibition of the lysosomal pathway of apoptosis. NF-kappaB can protect cells from death after TNF-R1 stimulation, by extinguishing cathepsin B activity in the cytosol. This activity of NF-kappaB is mediated, at least in part, by the upregulation of Serine protease inhibitor 2A (Spi2A), a potent inhibitor of cathepsin B. Indeed, Spi2A can substitute for NF-kappaB in suppressing the induction of cathepsin B activity in the cytosol. Thus, inhibition of cathepsin B by Spi2A is a mechanism by which NF-kappaB protects cells from lysosome-mediated apoptosis.
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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.