Acetylation-Deacetylation of the Transcription Factor Nrf2 (Nuclear Factor Erythroid 2-related Factor 2) Regulates Its Transcriptional Activity and Nucleocytoplasmic Localization

摘要: Activation of Nrf2 by covalent modifications that release it from its inhibitor protein Keap1 has been extensively documented. In contrast, may regulate action after have received little attention. Here we show CREB-binding induced acetylation Nrf2, increased binding to cognate response element in a target gene promoter, and Nrf2-dependent transcription promoters. Heterologous sirtuin 1 (SIRT1) decreased as well transcription, effects were overridden dominant negative SIRT1 (SIRT1-H355A). The SIRT1-selective inhibitors EX-527 nicotinamide stimulated whereas resveratrol, putative activator SIRT1, was inhibitory, mimicking the effect SIRT1. Mutating lysine alanine or arginine at Lys588 Lys591 resulted abrogated transcription-activating protein. Furthermore, had no on these mutants, indicating sites are sites. Microscope imaging GFP-Nrf2 HepG2 cells immunoblotting for showed conditions nuclear localization deacetylation enhanced cytoplasmic rather than localization. We posit nucleus undergoes acetylation, resulting binding, with basic-region leucine zipper protein(s), antioxidant consequently disengages element, thereby transcriptional termination subsequently export.