{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T20:35:17Z","timestamp":1791146117115,"version":"4.1.0"},"reference-count":46,"publisher":"Wiley","issue":"14","license":[{"start":{"date-parts":[[2013,6,18]],"date-time":"2013-06-18T00:00:00Z","timestamp":1371513600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["febs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FEBS Journal"],"published-print":{"date-parts":[[2013,7]]},"abstract":"\n \n \n Tumour necrosis factor (\n TNF<\/jats:styled-content>\n ) related apoptosis inducing ligand (\n TRAIL<\/jats:styled-content>\n ), a membrane\u2010bound ligand from the\n TNF<\/jats:styled-content>\n family, has attracted significant attention due to its rather specific and effective ability to induce apoptotic death in various types of cancer cells via binding to and activating its pro\u2010apoptotic death receptors. However, a significant number of primary cancer cells often develop resistance to\n TRAIL<\/jats:styled-content>\n treatment, and the signalling platform behind this phenomenon is not fully understood. Upon blocking endosomal acidification by the vacuolar\n ATP<\/jats:styled-content>\n ase (\n V<\/jats:styled-content>\n \u2010\n ATP<\/jats:styled-content>\n ase) inhibitors bafilomycin A1 (BafA1) or concanamycin A, we observed a significantly reduced initial sensitivity of several, mainly colorectal, tumour cell lines to\n TRAIL<\/jats:styled-content>\n \u2010induced apoptosis. In cells pretreated with these inhibitors, the\n TRAIL<\/jats:styled-content>\n \u2010induced processing of caspase\u20108 and the aggregation and trafficking of the\n TRAIL<\/jats:styled-content>\n receptor complexes were temporarily attenuated. Nuclear factor \u03baB or mitogen activated protein\/stress kinase signalling from the activated\n TRAIL<\/jats:styled-content>\n receptors remained unchanged, and neither possible lysosomal permeabilization nor acid sphingomyelinase was involved in this process. The cell surface expression of\n TRAIL<\/jats:styled-content>\n receptors and their\n TRAIL<\/jats:styled-content>\n \u2010induced internalization were not affected by\n V<\/jats:styled-content>\n \u2010\n ATP<\/jats:styled-content>\n ase inhibitors. The inhibitory effect of BafA1, however, was blunted by knockdown of the caspase\u20108 inhibitor c\n FLIP<\/jats:styled-content>\n . Altogether, the data obtained provide the first evidence that endosomal acidification could represent an important regulatory node in the proximal part of\n TRAIL<\/jats:styled-content>\n \u2010induced pro\u2010apoptotic signalling.\n <\/jats:p>\n <\/jats:sec>\n \n Structured digital abstract<\/jats:title>\n \n \n \n \n TRAIL<\/jats:ext-link>\n and\n Caspase-8<\/jats:ext-link>\n colocalize<\/jats:ext-link>\n by\n fluorescence microscopy<\/jats:ext-link>\n (\n View interaction<\/jats:ext-link>\n )\n <\/jats:p>\n <\/jats:list-item>\n \n \n TRAIL<\/jats:ext-link>\n physically interacts<\/jats:ext-link>\n with\n DR-5<\/jats:ext-link>\n ,\n Caspase-10<\/jats:ext-link>\n ,\n Caspase-8<\/jats:ext-link>\n ,\n cFLIP<\/jats:ext-link>\n and\n FADD<\/jats:ext-link>\n by\n pull down<\/jats:ext-link>\n (\n View interaction<\/jats:ext-link>\n )\n <\/jats:p>\n <\/jats:list-item>\n <\/jats:list>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/febs.12347","type":"journal-article","created":{"date-parts":[[2013,5,17]],"date-time":"2013-05-17T01:13:10Z","timestamp":1368753190000},"page":"3436-3450","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Inhibition of vacuolar\n ATP<\/scp>\n ase attenuates the\n TRAIL<\/scp>\n \u2010induced activation of caspase\u20108 and modulates the trafficking of\n TRAIL<\/scp>\n receptosomes"],"prefix":"10.1111","volume":"280","author":[{"given":"Vladimira","family":"Horova","sequence":"first","affiliation":[{"name":"Department of Cell Signalling and Apoptosis Institute of Molecular Genetics Academy of Sciences of the Czech Republic Prague Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nada","family":"Hradilova","sequence":"additional","affiliation":[{"name":"Department of Cell Signalling and Apoptosis Institute of Molecular Genetics Academy of Sciences of the 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