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Beschreibung
Nuclear factor erythroid 2-related factor 2 (UniProt: Q16236, also known as NF-E2-related factor 2, NFE2-related factor 2, HEBP1) is encoded by the NFE2L2 (also known as NRF2) gene in human. It is widely expressed with high expression in adult muscle, kidney, lung, liver and in fetal muscle. NFE2L2 is a transcription activator that binds to antioxidant response (ARE) elements in the promoter regions of target genes and is essential for the coordinated up-regulation of genes in response to oxidative stress. It contains an acidic activation domain in the N-terminus and DNA binding domain in the C-terminus. NFE2L2 is usually localized in the cytoplasm under unstressed conditions, but translocates to the nucleus when subjected to induction by electrophilic agents. Phosphorylation of Ser40 by protein kinase C in response to oxidative stress dissociates NFE2L2 from its cytoplasmic inhibitor KEAP1, thereby promoting its translocation into the nucleus. Acetylation at Lys596 and Lys599 increases its nuclear localization whereas deacetylation by SIRT1 enhances cytoplasmic presence. NFE2L2 is shown to be down-regulated by ENC1 via a proteasomal ubiquitin-independent protein catabolic process.
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