ArticleThe EMBO journal2007
FLASH links the CD95 signaling pathway to the cell nucleus and nuclear bodies.
Article in The EMBO journal, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 1 of them a synthesis that pooled it.
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Who cites it
36 citing papers in PubMed, 1 synthesis or guideline pooled it, 73 citations in OpenAlex.
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- On the Prevalence and Roles of Proteins Undergoing Liquid-Liquid Phase Separation in the Biogenesis of PML-Bodies.Biomolecules · 2023Article
- Review
- Deletion of hypoxia-responsive microRNA-210 results in a sex-specific decrease in nephron number.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020Article
- Lysine Acetylation Goes Global: From Epigenetics to Metabolism and Therapeutics.Chemical reviews · 2018Review
- Transcription factor E2F3a regulatesCancer cell international · 2018Article
- Genome-wide screen of cell-cycle regulators in normal and tumor cells identifies a differential response to nucleosome depletion.Cell cycle (Georgetown, Tex.) · 2017Article
- Protection of Human Umbilical Vein Endothelial Cells against Oxidative Stress by MicroRNA-210.Oxidative medicine and cellular longevity · 2017Article
- A subset of replication-dependent histone mRNAs are expressed as polyadenylated RNAs in terminally differentiated tissues.Nucleic acids research · 2016Article
- NLRP3 regulates a non-canonical platform for caspase-8 activation during epithelial cell apoptosis.Cell death and differentiation · 2016Article
- Role of the nucleus in apoptosis: signaling and execution.Cellular and molecular life sciences : CMLS · 2015Review
- Solution NMR structures of homeodomains from human proteins ALX4, ZHX1, and CASP8AP2 contribute to the structural coverage of the Human Cancer Protein Interaction Network.Journal of structural and functional genomics · 2014Article
- Extrinsic apoptosis is impeded by direct binding of the APL fusion protein NPM-RAR to TRADD.Molecular cancer research : MCR · 2014Article
- Benzene-poly-carboxylic acid complex, a novel anti-cancer agent induces apoptosis in human breast cancer cells.PloS one · 2014Article
- Article
- FLASH/casp8ap2 is indispensable for early embryogenesis but dispensable for proliferation and differentiation of ES cells.PloS one · 2014Article
- SUMO regulates proteasome-dependent degradation of FLASH/Casp8AP2.Cell cycle (Georgetown, Tex.) · 2013Article
- Caspase-8 binding to cardiolipin in giant unilamellar vesicles provides a functional docking platform for bid.PloS one · 2013Article
- Poly-small ubiquitin-like modifier (PolySUMO)-binding proteins identified through a string search.The Journal of biological chemistry · 2012Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Caspase-8-binding protein FLICE-associated huge protein (FLASH) has been proposed to regulate death receptor CD95-induced apoptosis through facilitating caspase-8 activation at the death-inducing signaling complex. Here, we found that FLASH interacts with the PML nuclear body component Sp100 and predominantly resides in the nucleus and nuclear bodies (NBs). In response to CD95 activation, FLASH leaves the NBs and translocates into the cytoplasm where it accumulates at mitochondria. The nucleo-cytoplasmic translocation of FLASH requires CD95-induced caspase activation and is facilitated by the Crm1-dependent nuclear export pathway. Downregulation of FLASH by RNA interference or inhibition of its nucleo-cytoplasmic shuttling reduced CD95-induced apoptosis. Furthermore, we show that the adenoviral anti-apoptotic Bcl-2 family member E1B19K traps FLASH and procaspase-8 in a ternary complex at mitochondria, thereby blocking CD95-induced caspase-8 activation. Knock-down of Sp100 potentiated CD95-activated apoptosis through enhancing nucleo-cytoplasmic FLASH translocation. In summary, our findings suggest that CD95 signals via a previously unrecognized nuclear pathway mediated by nucleo-cytoplasmic translocation of FLASH.
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Registered trials
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