FOXO3-induced reactive oxygen species are regulated by BCL2L11 (Bim) and SESN3

Journal of Cell Science
Judith HagenbuchnerMichael J Ausserlechner

Abstract

FOXO transcription factors induce apoptosis and regulate cellular production of reactive oxygen species (ROS). To identify the sequence of molecular events underlying FOXO3 (FKHRL1)-induced apoptosis, we studied the regulation and function of FOXO3 by expressing an ECFP-tagged FOXO3 or a 4OH-tamoxifen (4OHT)-inducible FOXO3-ERtm fusion protein in SH-EP and STA-NB15 neuronal cells. After knockdown of FOXO3 or expression of a dominant-negative FOXO3 mutant we observed that etoposide- and doxorubicin-induced elevation of cellular ROS depends on FOXO3 activation and induction of its transcriptional target BCL2L11 (Bim). Activation of FOXO3 on its own induced two sequential ROS waves as measured by reduced MitoTrackerRed in live cell microscopy. Induction of Bim by FOXO3 is essential for this phenomenon because Bim knockdown or ectopic expression of BCL2L1 (BclxL) prevented FOXO3-mediated overproduction of ROS and apoptosis. Tetracycline-controlled expression of Bim impaired mitochondrial respiration and caused ROS production, suggesting that FOXO3 induces uncoupling of mitochondrial respiration through Bim. FOXO3 also activated a ROS rescue pathway by inducing the peroxiredoxin SESN3 (Sestrin3), which is responsible for the biphasi...Continue Reading

References

Nov 15, 2000·American Journal of Physiology. Lung Cellular and Molecular Physiology·V J Thannickal, B L Fanburg
Jul 26, 2002·Archives of Biochemistry and Biophysics·Karen C Arden, William H Biggs
Sep 20, 2002·Nature·Geert J P L KopsBoudewijn M T Burgering
Feb 20, 2003·Proceedings of the National Academy of Sciences of the United States of America·Kui Lei, Roger J Davis
Mar 26, 2003·Seminars in Cancer Biology·Leigh Coultas, Andreas Strasser
Jan 28, 2004·Cell·Nika N Danial, Stanley J Korsmeyer
Aug 3, 2004·Science·Douglas R Green, Guido Kroemer
Oct 8, 2004·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Esther B E BeckerAzad Bonni
Nov 13, 2004·The EMBO Journal·Marieke A G EssersBoudewijn M T Burgering
Oct 18, 2005·Cytometry. Part a : the Journal of the International Society for Analytical Cytology·Rita NarathPeter F Ambros
Jul 11, 2006·Biochimica Et Biophysica Acta·Dmitry B ZorovSteven J Sollott
Aug 5, 2006·Cell Death and Differentiation·P ObexerM J Ausserlechner
Jan 20, 2007·Cancer Research·Daniela OpelSimone Fulda
Sep 7, 2007·Trends in Cell Biology·Ruth Scherz-Shouval, Zvulun Elazar
Jan 16, 2008·The Journal of Biological Chemistry·Calin B ChiribauDan Sorescu
Jan 24, 2008·Molecular and Cellular Biology·Andrey V KuznetsovJakob Troppmair
Mar 18, 2008·Nature Cell Biology·Wen-Bin TsaiMickey C-T Hu
Apr 9, 2008·Oncogene·D R Calnan, A Brunet
Apr 9, 2008·Oncogene·K K HoE W-F Lam
May 20, 2008·Biochemical and Biophysical Research Communications·Kazuhiro HasegawaHiroshi Itoh
Jun 10, 2008·Nature Protocols·Andrey V KuznetsovWolfram S Kunz
Sep 6, 2008·The Journal of Biological Chemistry·Wei-Qi TanPei-Feng Li
Feb 13, 2009·Molecular Biology of the Cell·Petra ObexerMichael Ausserlechner
Dec 24, 2009·The Journal of Biological Chemistry·Wenzhi BiZengqiang Yuan
Jul 1, 2011·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Lei XiaoZengqiang Yuan

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Citations

Apr 2, 2013·Archives of Toxicology·Krishnendu SinhaParames C Sil
Apr 12, 2012·Molecular Biology of the Cell·Kathrin GeigerPetra Obexer
Feb 12, 2014·Antioxidants & Redox Signaling·Rodrigo Portes UreshinoSoraya Soubhi Smaili
Dec 18, 2013·Journal of Molecular and Cellular Cardiology·Zhaokang ChengJoan M Taylor
Apr 17, 2014·Journal of Thoracic Oncology : Official Publication of the International Association for the Study of Lung Cancer·Kazutoshi IsobeSakae Homma
Mar 22, 2016·Hepatic Oncology·Josiah Cox, Steven Weinman
Dec 19, 2015·Oxidative Medicine and Cellular Longevity·Stéphanie Anaís CastaldoPatrícia Alexandra Madureira
Jul 7, 2015·Oncogene·J HagenbuchnerM J Ausserlechner
Sep 24, 2013·Cell Metabolism·Jun Hee LeeMichael Karin
Jun 21, 2017·International Journal of Cancer. Journal International Du Cancer·Wolfgang Link, Pablo J Fernandez-Marcos
Dec 4, 2019·ELife·Judith HagenbuchnerMichael J Ausserlechner

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