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Inhibition of vacuolar ATPase attenuates the TRAIL-induced activation of caspase-8 and modulates the trafficking of TRAIL receptosomes
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SYSNO ASEP 0422989 Druh ASEP J - Článek v odborném periodiku Zařazení RIV J - Článek v odborném periodiku Poddruh J Článek ve WOS Název Inhibition of vacuolar ATPase attenuates the TRAIL-induced activation of caspase-8 and modulates the trafficking of TRAIL receptosomes Tvůrce(i) Horová, Vladimíra (UMG-J)
Hradilová, Naďa (UMG-J)
Jelínková, Iva (BFU-R)
Koc, Michal (UMG-J)
Švadlenka, Jan (UMG-J)
Bražina, Jan (UMG-J)
Klíma, Martin (UMG-J)
Slavík, J. (CZ)
Vaculová, Alena (BFU-R) RID, ORCID
Anděra, Ladislav (UMG-J) RIDZdroj.dok. FEBS Journal - ISSN 1742-464X
Roč. 280, č. 14 (2013), s. 3436-3450Poč.str. 15 s. Jazyk dok. eng - angličtina Země vyd. GB - Velká Británie Klíč. slova acidification ; apoptosis ; caspase-8 ; TRAIL ; V-ATPase Vědní obor RIV EB - Genetika a molekulární biologie CEP GAP301/10/1971 GA ČR - Grantová agentura ČR GAP301/11/1730 GA ČR - Grantová agentura ČR 1M0506 GA MŠMT - Ministerstvo školství, mládeže a tělovýchovy Institucionální podpora UMG-J - RVO:68378050 ; BFU-R - RVO:68081707 UT WOS 000327128700023 DOI 10.1111/febs.12347 Anotace Tumour necrosis factor (TNF) related apoptosis inducing ligand (TRAIL), a membrane-bound ligand from the TNF 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-apoptotic death receptors. However, a significant number of primary cancer cells often develop resistance to TRAIL treatment, and the signalling platform behind this phenomenon is not fully understood. Upon blocking endosomal acidification by the vacuolar ATPase (V-ATPase) inhibitors bafilomycin A1 (BafA1) or concanamycin A, we observed a significantly reduced initial sensitivity of several, mainly colorectal, tumour cell lines to TRAIL-induced apoptosis. In cells pretreated with these inhibitors, the TRAIL-induced processing of caspase-8 and the aggregation and trafficking of the TRAIL receptor complexes were temporarily attenuated. Nuclear factor B or mitogen activated protein/stress kinase signalling from the activated TRAIL receptors remained unchanged, and neither possible lysosomal permeabilization nor acid sphingomyelinase was involved in this process. The cell surface expression of TRAIL receptors and their TRAIL-induced internalization were not affected by V-ATPase inhibitors. The inhibitory effect of BafA1, however, was blunted by knockdown of the caspase-8 inhibitor cFLIP. Altogether, the data obtained provide the first evidence that endosomal acidification could represent an important regulatory node in the proximal part of TRAIL-induced pro-apoptotic signalling. Pracoviště Ústav molekulární genetiky Kontakt Nikol Škňouřilová, nikol.sknourilova@img.cas.cz, Tel.: 241 063 217 Rok sběru 2014
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