About: Hippo/Mst1 Stimulates Transcription of the Proapoptotic Mediator NOXA in a FoxO1-Dependent Manner     Goto   Sponge   NotDistinct   Permalink

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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)
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)
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)
skos:notation
  • RIV/00216208:11310/11:10104483!RIV12-MSM-11310___
http://linked.open...avai/predkladatel
http://linked.open...avai/riv/aktivita
http://linked.open...avai/riv/aktivity
  • P(GA204/08/0811), P(GAP301/10/1937), P(IAA500520702), P(KJB500970904), Z(AV0Z50110509), Z(AV0Z50520701), Z(MSM0021620857)
http://linked.open...iv/cisloPeriodika
  • 3
http://linked.open...vai/riv/dodaniDat
http://linked.open...aciTvurceVysledku
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http://linked.open...iv/duvernostUdaju
http://linked.open...titaPredkladatele
http://linked.open...dnocenehoVysledku
  • 202116
http://linked.open...ai/riv/idVysledku
  • RIV/00216208:11310/11:10104483
http://linked.open...riv/jazykVysledku
http://linked.open.../riv/klicovaSlova
  • alpha-tocopherylsuccinate; FoxOproteins; Mst1 kinase (en)
http://linked.open.../riv/klicoveSlovo
http://linked.open...odStatuVydavatele
  • US - Spojené státy americké
http://linked.open...ontrolniKodProRIV
  • [98243AD57E3E]
http://linked.open...i/riv/nazevZdroje
  • Cancer Research
http://linked.open...in/vavai/riv/obor
http://linked.open...ichTvurcuVysledku
http://linked.open...cetTvurcuVysledku
http://linked.open...vavai/riv/projekt
http://linked.open...UplatneniVysledku
http://linked.open...v/svazekPeriodika
  • 71
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
http://linked.open...ain/vavai/riv/wos
  • 000286830300034
http://linked.open...n/vavai/riv/zamer
issn
  • 0008-5472
number of pages
http://bibframe.org/vocab/doi
  • 10.1158/0008-5472.CAN-10-2203
http://localhost/t...ganizacniJednotka
  • 11310
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