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The unique topobiology of Nrf1 dictates its multistep processing into a mature activator that is paved as a new strategic avenue to prevent and treat cancer

The unique topobiology of Nrf1 dictates its multistep proces...

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2018环境与健康学术会议--精准环境健康：跨学科合作的挑战

作者： Yiguo Zhang Laboratory of Cell Biochemistry and Topogenetic Regulation College of Bioengineering and Faculty of SciencesChongqing University

The unique topobiology of the transmembrane-bound Nrfl transcription factor with dynamic transient phases controls its multistep processing to yield distinct lengths of isoforms(***) during the maturation of this CNC-bZIP protein into an activator,enabling for its ER-to-nuclear translocation in order to gain access to cognate ARE/EpRE-driven genes before being ***-accumulating evidence demonstrates that Nrfl acts as an unique vital player in maintaining cellular(redox,lipid and protein) homeostasis and organ integrity during normal development and healthy growth throughout the whole life ***,loss-of-function of Nrfl results in severe oxidative stress,genomic instability,embryonic lethality,developmental disorders,and adult diseases such as non-alcoholic steatohepatitis,hepatocellular carcinoma,diabetes and neurogenerative ***,Nrfl is critically implicated in a variety of important physio-pathological processes by governing robust target genes in order to reinforce antioxidant,detoxification and cytoprotective responses to cellular ***,there also exists a proteasomal’bounce-back’ response mediated by Nrfl,insofar as to enhance the drug resistance to proteasomal inhibitors in preclinical treatment of neuroblastoma,multiple myeloma and triple-negative breast ***,several drugs or chemicals are found or re-found in some new ways to block the proteasomal compensatory pathway through inhibiting the multistep processing of ***,induction of Nrfl activity by some drugs or chemicals leads to cytoprotection from cell apoptosis and promotes cell *** is a good start of the constructive and meaningful studies to explore the mechanism(s) by which Nrfl is activated to protect neurons and other cells from malignant and degenerative ***,Nrfl has appealed attentions as a new attractive therapeutic strategy for human cancers and other diseases.

关键词： Nrf1 topobiology cancer chemoprevention therapy

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