Nrf3 promotes UV-induced keratinocyte apoptosis through suppression of cell adhesion

Cell Death and Differentiation
Beat SiegenthalerSabine Werner

Abstract

The transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) is a key regulator of the cellular stress response, but the biological functions of the related Nrf3 protein are largely unknown. Here we demonstrate a novel pro-apoptotic function of Nrf3 in mouse and human keratinocytes. In response to UV irradiation, Nrf3-deficient keratinocytes were protected from apoptosis in vitro and in vivo. The protective function was also seen under oxidative or hyperosmotic stress conditions, but not when apoptosis was induced by disruption of cell-matrix interactions. Mechanistically, we show that Nrf3-deficient keratinocytes exhibit stronger cell-cell and cell-matrix adhesion, which correlates with higher cell surface integrin levels and enhanced activation of focal adhesion kinase. Nrf3-deficient cells also formed more and larger focal adhesions and exhibited a higher motility. These results suggest that the strong expression of Nrf3 in basal keratinocytes promotes their elimination in response to DNA damage-inducing agents, thereby preventing accumulation of mutated stem and transit amplifying cells in the epidermis.

References

Mar 1, 1988·The Journal of Cell Biology·P BoukampN E Fusenig
Aug 1, 1996·The Journal of Cell Biology·S M FrischP Y Chan-Hui
Nov 26, 1996·Proceedings of the National Academy of Sciences of the United States of America·K ChanY W Kan
Jun 27, 1998·The Journal of Biological Chemistry·F G GervaisS Roy
Feb 26, 1999·The Journal of Biological Chemistry·A KobayashiM Yamamoto
Apr 3, 2004·Molecular and Cellular Biology·Anna DerjugaVolker Blank
Sep 30, 2006·The Journal of Investigative Dermatology·Moritz DurchdewaldUlrich auf dem Keller
Nov 30, 2006·Cancer Science·Hozumi Motohashi, Masayuki Yamamoto
Oct 25, 2007·Proceedings of the National Academy of Sciences of the United States of America·Paul TalalayAlbena T Dinkova-Kostova
Jul 3, 2009·Current Opinion in Cell Biology·Andrew P GilmoreJennefer Lindsay
Jan 23, 2010·Circulation Research·Anna Elena PepeQingbo Xu
Mar 11, 2010·Science Signaling·Gerasimos P Sykiotis, Dirk Bohmann
May 19, 2010·Genes & Development·Matthias SchäferSabine Werner
Dec 15, 2010·Blood·Grégory ChevillardVolker Blank
Jan 13, 2011·Journal of Cell Science·Daniel V MoikReinhard Fässler
Sep 21, 2012·Journal of Cell Science·Michael MeyerSabine Werner
Dec 21, 2012·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Dong-Hwee Kim, Denis Wirtz
Nov 15, 2013·The Journal of Immunology : Official Journal of the American Association of Immunologists·Maria AntsiferovaSabine Werner
Jan 7, 2015·The Journal of Investigative Dermatology·Gabriel SollbergerHans-Dietmar Beer
Apr 7, 2015·The American Journal of Pathology·Jitka SulcovaSabine Werner
Apr 29, 2015·Free Radical Biology & Medicine·Matthias Schäfer, Sabine Werner
Jan 1, 2016·Diabetes·Min LongDonna D Zhang
Oct 4, 2017·Scientific Reports·A M Masudul Azad ChowdhuryAkira Kobayashi

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Citations

Aug 11, 2019·International Journal of Molecular Sciences·Paul Hiebert, Sabine Werner
Jul 8, 2020·Animals : an Open Access Journal From MDPI·Rui-Yi ChenChung-Der Hsiao
Dec 28, 2021·IUBMB Life·Marianna KapetanouEfstathios S Gonos

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Methods Mentioned

BETA
flow cytometry
nuclear translocation
Flow
electron microscopy
transfection

Software Mentioned

Leica
Prism
Zeiss
GraphPad
Axiovision

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