부산대학교 도서관

Cellular detoxication is essential for healthbecause it provides protection against various chemicalsand xenobiotics. The KEAP1–NRF2 system is important forcellular defense against oxidative and electrophilic stressesas NRF2 activates the transcription of an array of cytoprotectivegenes, including drug-metabolizing and antioxidantenzymes, in a stress-dependent manner. The CNC family oftranscription factors, including NRF2, form heterodimerswith small Maf (sMaf) proteins and bind to consensus DNAsequences that have been referred to as antioxidant responseelement, electrophile response element, or NF-E2-bindingelement. These sequences are now collectively called CNC–sMaf binding element (CsMBE). In addition to forming aheterodimer with CNC proteins, sMaf proteins can formhomodimers and recognize regulatory motifs called Maf recognitionelement (MARE). Although the CsMBE sequencesubstantially overlaps with that of MARE, the sequencesdiffer. NRF2 selectively recognizes CsMBE, which is criticalfor cytoprotection. Recent advances in high-throughputsequencing and population-scale genome analysis providenew insights into the transcriptional regulation involved inthe stress response. The integration of a genome-wide mapof NRF2 occupancy with disease-susceptibility loci revealsthe associations between polymorphisms in CsMBE and diseaserisk, information useful for the personalized medicineof the future.