The NRF2-related interactome and regulome contain multifunctional proteins and fine-tuned autoregulatory loops

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• 作者：Di&aacute ; na Papp^a ; ^b ; ¹ ; Katalin Lenti^c ; ¹ ; Dezs艖 Mó ; dos^a ; ^b ; ^c ; D&aacute ; vid Fazekas^a ; Zolt&aacute ; n Dú ; l^a ; Dé ; nes Tü ; rei^a ; ^b ; L&aacute ; szló ; Fö ; ldv&aacute ; ri-Nagy^a ; Ruth Nussinov^d ; ^e ; Pé ; ter Csermely^b ; Tam&aacute ; s Korcsm&aacute ; ros^a ; ^b ; ^{korcsmaros@netbiol.elte.hu}
• 关键词：NRF2 ; Protein&ndash ; protein interaction ; Interaction prediction ; Regulatory loops ; Signaling network ; Double-edged sword
• 刊名：FEBS Letters
• 出版年：2012
• 期刊代码：70_00145793
• 类别：bio
• 出版时间：21 June, 2012
• 卷：586
• 期：13
• 页码：1795-1802
• 文件大小：2099 K

摘要

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.