激活转录因子3是核因子红系衍生2相关因子2（Nrf2）调控的应激通路的新型抑制因子。

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

作者信息

Brown Stephan L, Sekhar Konjeti R, Rachakonda Girish, Sasi Soumya, Freeman Michael L

机构信息

Department of Radiation Oncology and Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA.

出版信息

Cancer Res. 2008 Jan 15;68(2):364-8. doi: 10.1158/0008-5472.CAN-07-2170.

DOI:10.1158/0008-5472.CAN-07-2170

PMID:18199529

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.

摘要

转录因子核因子红系衍生2相关因子2（Nrf2）与位于靶基因启动子区域的抗氧化反应元件（ARE）处的环磷酸腺苷反应元件结合蛋白（CBP）复合时，可调节广泛的细胞应激反应网络的诱导。活化转录因子3（ATF3）能够以一种尚不清楚的方式抑制Nrf2介导的信号传导。在此，我们表明ATF3介导的抑制作用是ATF3与Nrf2直接蛋白质-蛋白质相互作用的结果，这种相互作用导致CBP从ARE上解离。这项工作确立了ATF3作为Nrf2导向的应激反应途径的新型抑制因子。