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

Diána Papp, Katalin Lenti, Dezso Módos, Dávid Fazekas, Zoltán Dúl, Dénes Türei, László Földvári-Nagy, Ruth Nussinov, Péter Csermely, Tamás Korcsmáros

Research output: Contribution to journalArticle

64 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1795-1802
Number of pages8
JournalFEBS letters
Volume586
Issue number13
DOIs
Publication statusPublished - Jun 21 2012

Keywords

  • Double-edged sword
  • Interaction prediction
  • NRF2
  • Protein-protein interaction
  • Regulatory loops
  • Signaling network

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

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    Papp, D., Lenti, K., Módos, D., Fazekas, D., Dúl, Z., Türei, D., Földvári-Nagy, L., Nussinov, R., Csermely, P., & Korcsmáros, T. (2012). The NRF2-related interactome and regulome contain multifunctional proteins and fine-tuned autoregulatory loops. FEBS letters, 586(13), 1795-1802. https://doi.org/10.1016/j.febslet.2012.05.016