Abstract
The transcription factor nuclear factor erythroid-derived 2-related factor 2 (Nrf2) regulates induction of an extensive cellular stress response network when complexed with the cAMP-responsive element binding protein (CBP) at antioxidant response elements (ARE) located in the promoter region of target genes. Activating transcription factor 3 (ATF3) can repress Nrf2-mediated signaling in a manner that is not well understood. Here, we show that ATF3-mediated suppression is a consequence of direct ATF3-Nrf2 protein-protein interactions that result in displacement of CBP from the ARE. This work establishes ATF3 as a novel repressor of the Nrf2-directed stress response pathway.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Activating Transcription Factor 3 / antagonists & inhibitors
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Activating Transcription Factor 3 / genetics
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Activating Transcription Factor 3 / metabolism
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Activating Transcription Factor 3 / physiology*
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Animals
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Antioxidants / pharmacology
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Cells, Cultured
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Gene Expression Regulation*
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Mice
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NF-E2-Related Factor 2 / antagonists & inhibitors
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NF-E2-Related Factor 2 / metabolism
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NF-E2-Related Factor 2 / physiology*
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Protein Binding
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RNA, Small Interfering / pharmacology
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Repressor Proteins / metabolism
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Repressor Proteins / physiology
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Response Elements / drug effects
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Signal Transduction / genetics
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Stress, Physiological / genetics*
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Transfection
Substances
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Activating Transcription Factor 3
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Antioxidants
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NF-E2-Related Factor 2
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Nfe2l2 protein, mouse
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RNA, Small Interfering
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Repressor Proteins