Activating transcription factor 3 is a novel repressor of the nuclear factor erythroid-derived 2-related factor 2 (Nrf2)-regulated stress pathway.

Brown SL, Sekhar KR, Rachakonda G, Sasi S, Freeman ML
Cancer Res. 2008 68 (2): 364-8

PMID: 18199529 · DOI:10.1158/0008-5472.CAN-07-2170

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.

MeSH Terms (14)

Activating Transcription Factor 3 Animals Antioxidants Cells, Cultured Gene Expression Regulation Mice NF-E2-Related Factor 2 Protein Binding Repressor Proteins Response Elements RNA, Small Interfering Signal Transduction Stress, Physiological Transfection

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