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Nrf3 promotes UV-induced keratinocyte apoptosis through suppression of cell adhesion
by
Schäfer, Matthias
, Tanner, Sandra
, Werner, Sabine
, Bloch, Wilhelm
, Beer, Hans-Dietmar
, Meyer, Michael
, Muzumdar, Sukalp
, Blank, Volker
, Siegenthaler, Beat
, Defila, Claudia
in
13/2
/ 631/80/79
/ 64/60
/ 692/308/1426
/ 82
/ 82/51
/ 96
/ 96/106
/ 96/31
/ Animals
/ Apoptosis
/ Apoptosis - radiation effects
/ Basic-Leucine Zipper Transcription Factors - antagonists & inhibitors
/ Basic-Leucine Zipper Transcription Factors - genetics
/ Basic-Leucine Zipper Transcription Factors - metabolism
/ Biochemistry
/ Biomedical and Life Sciences
/ Cell adhesion
/ Cell adhesion & migration
/ Cell Adhesion - radiation effects
/ Cell Biology
/ Cell Cycle Analysis
/ Cell Movement - radiation effects
/ Cell surface
/ Cellular stress response
/ DNA damage
/ Epidermis
/ Epidermis - metabolism
/ Epidermis - pathology
/ Epidermis - radiation effects
/ Epidermis - ultrastructure
/ Female
/ Focal adhesion kinase
/ Focal Adhesion Kinase 1 - metabolism
/ Humans
/ Keratinocytes
/ Keratinocytes - cytology
/ Keratinocytes - metabolism
/ Keratinocytes - radiation effects
/ Life Sciences
/ Mice
/ Mice, Inbred C57BL
/ Mice, Knockout
/ NF-E2-Related Factor 2 - deficiency
/ NF-E2-Related Factor 2 - genetics
/ Reactive Oxygen Species - metabolism
/ RNA Interference
/ RNA, Small Interfering - metabolism
/ Signal Transduction - radiation effects
/ Stem Cells
/ Ultraviolet radiation
/ Ultraviolet Rays
/ Wound Healing
2018
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Nrf3 promotes UV-induced keratinocyte apoptosis through suppression of cell adhesion
by
Schäfer, Matthias
, Tanner, Sandra
, Werner, Sabine
, Bloch, Wilhelm
, Beer, Hans-Dietmar
, Meyer, Michael
, Muzumdar, Sukalp
, Blank, Volker
, Siegenthaler, Beat
, Defila, Claudia
in
13/2
/ 631/80/79
/ 64/60
/ 692/308/1426
/ 82
/ 82/51
/ 96
/ 96/106
/ 96/31
/ Animals
/ Apoptosis
/ Apoptosis - radiation effects
/ Basic-Leucine Zipper Transcription Factors - antagonists & inhibitors
/ Basic-Leucine Zipper Transcription Factors - genetics
/ Basic-Leucine Zipper Transcription Factors - metabolism
/ Biochemistry
/ Biomedical and Life Sciences
/ Cell adhesion
/ Cell adhesion & migration
/ Cell Adhesion - radiation effects
/ Cell Biology
/ Cell Cycle Analysis
/ Cell Movement - radiation effects
/ Cell surface
/ Cellular stress response
/ DNA damage
/ Epidermis
/ Epidermis - metabolism
/ Epidermis - pathology
/ Epidermis - radiation effects
/ Epidermis - ultrastructure
/ Female
/ Focal adhesion kinase
/ Focal Adhesion Kinase 1 - metabolism
/ Humans
/ Keratinocytes
/ Keratinocytes - cytology
/ Keratinocytes - metabolism
/ Keratinocytes - radiation effects
/ Life Sciences
/ Mice
/ Mice, Inbred C57BL
/ Mice, Knockout
/ NF-E2-Related Factor 2 - deficiency
/ NF-E2-Related Factor 2 - genetics
/ Reactive Oxygen Species - metabolism
/ RNA Interference
/ RNA, Small Interfering - metabolism
/ Signal Transduction - radiation effects
/ Stem Cells
/ Ultraviolet radiation
/ Ultraviolet Rays
/ Wound Healing
2018
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Nrf3 promotes UV-induced keratinocyte apoptosis through suppression of cell adhesion
by
Schäfer, Matthias
, Tanner, Sandra
, Werner, Sabine
, Bloch, Wilhelm
, Beer, Hans-Dietmar
, Meyer, Michael
, Muzumdar, Sukalp
, Blank, Volker
, Siegenthaler, Beat
, Defila, Claudia
in
13/2
/ 631/80/79
/ 64/60
/ 692/308/1426
/ 82
/ 82/51
/ 96
/ 96/106
/ 96/31
/ Animals
/ Apoptosis
/ Apoptosis - radiation effects
/ Basic-Leucine Zipper Transcription Factors - antagonists & inhibitors
/ Basic-Leucine Zipper Transcription Factors - genetics
/ Basic-Leucine Zipper Transcription Factors - metabolism
/ Biochemistry
/ Biomedical and Life Sciences
/ Cell adhesion
/ Cell adhesion & migration
/ Cell Adhesion - radiation effects
/ Cell Biology
/ Cell Cycle Analysis
/ Cell Movement - radiation effects
/ Cell surface
/ Cellular stress response
/ DNA damage
/ Epidermis
/ Epidermis - metabolism
/ Epidermis - pathology
/ Epidermis - radiation effects
/ Epidermis - ultrastructure
/ Female
/ Focal adhesion kinase
/ Focal Adhesion Kinase 1 - metabolism
/ Humans
/ Keratinocytes
/ Keratinocytes - cytology
/ Keratinocytes - metabolism
/ Keratinocytes - radiation effects
/ Life Sciences
/ Mice
/ Mice, Inbred C57BL
/ Mice, Knockout
/ NF-E2-Related Factor 2 - deficiency
/ NF-E2-Related Factor 2 - genetics
/ Reactive Oxygen Species - metabolism
/ RNA Interference
/ RNA, Small Interfering - metabolism
/ Signal Transduction - radiation effects
/ Stem Cells
/ Ultraviolet radiation
/ Ultraviolet Rays
/ Wound Healing
2018
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Nrf3 promotes UV-induced keratinocyte apoptosis through suppression of cell adhesion
Journal Article
Nrf3 promotes UV-induced keratinocyte apoptosis through suppression of cell adhesion
2018
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Overview
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.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ 64/60
/ 82
/ 82/51
/ 96
/ 96/106
/ 96/31
/ Animals
/ Apoptosis - radiation effects
/ Basic-Leucine Zipper Transcription Factors - antagonists & inhibitors
/ Basic-Leucine Zipper Transcription Factors - genetics
/ Basic-Leucine Zipper Transcription Factors - metabolism
/ Biomedical and Life Sciences
/ Cell Adhesion - radiation effects
/ Cell Movement - radiation effects
/ Epidermis - radiation effects
/ Female
/ Focal Adhesion Kinase 1 - metabolism
/ Humans
/ Keratinocytes - radiation effects
/ Mice
/ NF-E2-Related Factor 2 - deficiency
/ NF-E2-Related Factor 2 - genetics
/ Reactive Oxygen Species - metabolism
/ RNA, Small Interfering - metabolism
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