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rdf:type
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rdfs:seeAlso
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Description
| - Previous studies of the cytotoxic effects of alpha-tocopheryl succinate (alpha-TOS) on cancer cells identified a mechanism whereby alpha-TOS caused apoptosis requiring the Noxa-Bak axis. In the present study, ab initio analysis revealed a conserved FoxO-binding site in the NOXA promoter, and specific affinity of FoxO proteins to this site was confirmed by fluorescence anisotropy. FoxO1 and FoxO3a proteins accumulated in the nucleus of alpha-TOS-treated cells, and the specific FoxO1 association with the NOXA promoter and its activation were validated by chromatin immunoprecipitation. Using siRNA knockdown, a specific role for the FoxO1 protein in activating NOXA transcription was identified. The proapoptotic kinase Hippo/Mst1 was found to be strongly activated by alpha-TOS, and inhibiting Hippo/Mst1 by specific siRNA prevented phosphorylation of FoxO1 and its nuclear translocation. Thus, alpha-TOS induce apoptosis by a mechanism involving the Hippo/Mst1-FoxO1-Noxa pathway.
- Previous studies of the cytotoxic effects of alpha-tocopheryl succinate (alpha-TOS) on cancer cells identified a mechanism whereby alpha-TOS caused apoptosis requiring the Noxa-Bak axis. In the present study, ab initio analysis revealed a conserved FoxO-binding site in the NOXA promoter, and specific affinity of FoxO proteins to this site was confirmed by fluorescence anisotropy. FoxO1 and FoxO3a proteins accumulated in the nucleus of alpha-TOS-treated cells, and the specific FoxO1 association with the NOXA promoter and its activation were validated by chromatin immunoprecipitation. Using siRNA knockdown, a specific role for the FoxO1 protein in activating NOXA transcription was identified. The proapoptotic kinase Hippo/Mst1 was found to be strongly activated by alpha-TOS, and inhibiting Hippo/Mst1 by specific siRNA prevented phosphorylation of FoxO1 and its nuclear translocation. Thus, alpha-TOS induce apoptosis by a mechanism involving the Hippo/Mst1-FoxO1-Noxa pathway. (en)
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Title
| - Hippo/Mst1 Stimulates Transcription of the Proapoptotic Mediator NOXA in a FoxO1-Dependent Manner
- Hippo/Mst1 Stimulates Transcription of the Proapoptotic Mediator NOXA in a FoxO1-Dependent Manner (en)
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skos:prefLabel
| - Hippo/Mst1 Stimulates Transcription of the Proapoptotic Mediator NOXA in a FoxO1-Dependent Manner
- Hippo/Mst1 Stimulates Transcription of the Proapoptotic Mediator NOXA in a FoxO1-Dependent Manner (en)
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skos:notation
| - RIV/00216208:11310/11:10104483!RIV12-MSM-11310___
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http://linked.open...avai/predkladatel
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http://linked.open...avai/riv/aktivita
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http://linked.open...avai/riv/aktivity
| - P(GA204/08/0811), P(GAP301/10/1937), P(IAA500520702), P(KJB500970904), Z(AV0Z50110509), Z(AV0Z50520701), Z(MSM0021620857)
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http://linked.open...iv/cisloPeriodika
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http://linked.open...vai/riv/dodaniDat
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http://linked.open...aciTvurceVysledku
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http://linked.open.../riv/druhVysledku
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http://linked.open...iv/duvernostUdaju
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http://linked.open...titaPredkladatele
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http://linked.open...dnocenehoVysledku
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http://linked.open...ai/riv/idVysledku
| - RIV/00216208:11310/11:10104483
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http://linked.open...riv/jazykVysledku
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http://linked.open.../riv/klicovaSlova
| - alpha-tocopherylsuccinate; FoxOproteins; Mst1 kinase (en)
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http://linked.open.../riv/klicoveSlovo
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http://linked.open...odStatuVydavatele
| - US - Spojené státy americké
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http://linked.open...ontrolniKodProRIV
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http://linked.open...i/riv/nazevZdroje
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http://linked.open...in/vavai/riv/obor
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http://linked.open...ichTvurcuVysledku
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http://linked.open...cetTvurcuVysledku
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http://linked.open...vavai/riv/projekt
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http://linked.open...UplatneniVysledku
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http://linked.open...v/svazekPeriodika
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http://linked.open...iv/tvurceVysledku
| - Neužil, Jiří
- Obšil, Tomáš
- Rohlena, Jakub
- Truksa, Jaroslav
- Bouřa, Evžen
- Chladová, Jaromíra
- Dong, Lan-Feng
- Procházka, Lubomír
- Ralph, Stephen J.
- Vališ, Karel
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http://linked.open...ain/vavai/riv/wos
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http://linked.open...n/vavai/riv/zamer
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issn
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number of pages
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http://bibframe.org/vocab/doi
| - 10.1158/0008-5472.CAN-10-2203
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http://localhost/t...ganizacniJednotka
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is http://linked.open...avai/riv/vysledek
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