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Hippo/Mst1 stimulates transcription of the proapoptotic mediator NOXA in a FoxO1-dependent manner
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SYSNO ASEP 0358947 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Hippo/Mst1 stimulates transcription of the proapoptotic mediator NOXA in a FoxO1-dependent manner Author(s) Vališ, Karel (BTO-N)
Procházka, L. (CZ)
Bouřa, Evžen (FGU-C)
Chladová, Jaromíra (BTO-N) RID
Obšil, T. (CZ)
Rohlena, Jakub (BTO-N) RID, ORCID
Truksa, Jaroslav (BTO-N) RID, ORCID
Dong, L.F. (AU)
Ralph, S.J. (AU)
Neužil, Jiří (BTO-N) RIDSource Title Cancer Research. - : American Association for Cancer Research - ISSN 0008-5472
Roč. 71, č. 3 (2011), s. 946-954Number of pages 9 s. Language eng - English Country US - United States Keywords Mst1 kinase ; FoxO proteins ; alpha-tocopheryl succinate Subject RIV FD - Oncology ; Hematology R&D Projects KJB500970904 GA AV ČR - Academy of Sciences of the Czech Republic (AV ČR) GA204/08/0811 GA ČR - Czech Science Foundation (CSF) IAA500520702 GA AV ČR - Academy of Sciences of the Czech Republic (AV ČR) GAP301/10/1937 GA ČR - Czech Science Foundation (CSF) CEZ AV0Z50520701 - BTO-N (2007-2013) AV0Z50110509 - FGU-C (2005-2011) UT WOS 000286830300034 DOI 10.1158/0008-5472.CAN-10-2203 Annotation 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 Workplace Institute of Biotechnology Contact Monika Kopřivová, Monika.Koprivova@ibt.cas.cz, Tel.: 325 873 700 Year of Publishing 2011
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