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We are analyzing https://www.nature.com/articles/1208901.

Title:
JunD activates transcription of the human ferritin H gene through an antioxidant response element during oxidative stress | Oncogene
Description:
Ferritin is the major intracellular iron storage protein that sequesters excess free iron to minimize generation of iron-catalysed reactive oxygen species. We previously demonstrated that expression of ferritin heavy chain (ferritin H) was induced by pro-oxidants, which is a part of cellular antioxidant response to protect cells from oxidative damage. In this study, we have identified that the antioxidant/electrophile response element (ARE) located 4.5 kb upstream to the human ferritin H transcription initiation site is responsible for the oxidant response. The human ferritin H ARE comprises two copies of bidirectional AP1 motifs. Mutations in each AP1 motif significantly impaired protein binding and the function of the ARE, indicating that both of the AP1 motifs are required for pro-oxidant-mediated activation of the ferritin H gene. We identified that JunD, an AP1 family basic-leucine zipper (bZip) transcription factor, is one of the ferritin H ARE binding proteins and activates ferritin H transcription in HepG2 hepatocarcinoma cells. Gel retardation assay demonstrated that H2O2 (hydrogen peroxide) or t-BHQ (tert-butylhydroquinone) treatment increased total protein binding as well as JunD binding to the ferritin H ARE. Chromatin immunoprecipitation assay showed that H2O2 treatment induced JunD binding to the ferritin H ARE. Both H2O2 and t-BHQ induced phosphorylation of JunD at Ser-100, an activated form of JunD. Furthermore, overexpression of JunD induced endogenous ferritin H protein synthesis. Since JunD has recently been demonstrated to protect cells from several stress stimuli including oxidative stress, these results suggest that, in addition to NFE2-related factor 2 (Nrf2) as a major ARE regulatory protein, JunD is another ARE regulatory protein for transcriptional activation of the human ferritin H gene and probably other antioxidant genes containing the conserved ARE sequences by which JunD may confer cytoprotection during oxidative stress.
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Keywords {πŸ”}

biol, torti, chem, ferritin, nature, tsuji, jund, biochem, access, article, mol, cell, content, oncogene, oxidative, protein, arosio, sci, usa, cookies, human, stress, levi, proc, natl, acad, miller, privacy, transcription, gene, response, iron, binding, open, beaumont, jaiswal, pickett, research, data, antioxidant, induced, cells, med, cozzi, santambrogio, albertini, biophys, pharmacol, advertising, information,

Topics {βœ’οΈ}

nature portfolio permissions reprints privacy policy nature advertising social media author information authors author correspondence 2025 genome-wide meta-analysis t-bhq induced phosphorylation springerlink instant access personal data antioxidant/electrophile response element pro-oxidant-mediated activation data protection permissions nfe2l2/ap-1 targets expression iron status biomarkers privacy ferritin heavy chain issue learn bidirectional ap1 motifs recombinant protein ferritin explore content subscription content antioxidant response element european economic area cellular antioxidant response institutional subscriptions read dinkova-kostova archives accepting optional cookies article purchase journals search log nfe2-related factor 2 dr kazushi inoue article tsuji access hepg2 hepatocarcinoma cells article cite jund activates transcription manage preferences choi h https basal conditions oxidative stress transcription initiation site human ferritin content journal publish hydrogen peroxide

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