Journal
FEBS LETTERS
Volume 586, Issue 13, Pages 1795-1802Publisher
WILEY
DOI: 10.1016/j.febslet.2012.05.016
Keywords
NRF2; Protein-protein interaction; Interaction prediction; Regulatory loops; Signaling network; Double-edged sword
Funding
- National Cancer Institute, National Institutes of Health [HHSN261200800001E]
- EU-ESF grant [TAMOP 4.2.1./B-09/1/KMR-2010-0003, TAMOP-4.2.2/B-10/1-2010-0013]
- Hungarian Scientific Research Fund [OTKA K83314]
- Hungarian Research and Technology Office [5LET-08-2-2009-0041]
- NIH, National Cancer Institute, Center for Cancer Research
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NRF2 is a well-known, master transcription factor (TF) of oxidative and xenobiotic stress responses. Recent studies uncovered an even wider regulatory role of NRF2 influencing carcinogenesis, inflammation and neurodegeneration. Prompted by these advances here we present a systems-level resource for NRF2 interactome and regulome that includes 289 protein-protein, 7469 TF-DNA and 85 miRNA interactions. As systems-level examples of NRF2-related signaling we identified regulatory loops of NRF2 interacting proteins (e. g., JNK1 and CBP) and a fine-tuned regulatory system, where 35 TFs regulated by NRF2 influence 63 miRNAs that down-regulate NRF2. The presented network and the uncovered regulatory loops may facilitate the development of efficient, NRF2-based therapeutic agents. (C) 2012 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.
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