The NRF2-related interactome and regulome contain multifunctional proteins and fine-tuned autoregulatory loops.
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.
Department of Genetics, Eötvös Loránd University, Budapest, Hungary.
Diána
D
Papp
Katalin
K
Lenti
Dezső
D
Módos
Dávid
D
Fazekas
Zoltán
Z
Dúl
Dénes
D
Türei
László
L
Földvári-Nagy
Ruth
R
Nussinov
Péter
P
Csermely
Tamás
T
Korcsmáros
D001665:Binding Sites; D053263:Gene Regulatory Networks; D006706:Homeostasis; D035683:MicroRNAs / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
D035683:MicroRNAs; D051267:NF-E2-Related Factor 2; D014157:Transcription Factors