PIAS3 Interacts with ATF1 and Regulates the Human Ferritin H Gene through an Antioxidant-responsive Element
Open accessAbstract
Gene transcription is coordinately regulated by the balance between activation and repression mechanisms in response to various external stimuli. Ferritin, composed of H and L subunits, is the major intracellular iron storage protein involved in iron homeostasis. We previously identified an enhancer, termed antioxidant-responsive element (ARE), in the human ferritin H gene and its respective transcriptional activators including Nrf2 and JunD. Here we found that ATF1 (activating transcription factor 1) is a transcriptional repressor of the ferritin H ARE. Subsequent yeast two-hybrid screening identified PIAS3 (protein inhibitor of activated STAT3) as an ATF1-binding protein. Further investigation of the human ferritin H ARE regulation showed that 1) PIAS3 reversed ATF1-mediated repression of the ferritin H ARE; 2) ATF1 was sumoylated, but PIAS3, a SUMO E3 ligase, did not appear to play a major role in SUMO1-mediated ATF1 sumoylation or ATF1 transcription activating function; 3) PIAS3 decreased ATF1 binding to the ARE; and 4) ATF1 knockdown with siRNA increased ferritin H expression, whereas PIAS3 knockdown decreased basal expression and oxidative stress-mediated induction of ferritin H. These results suggest that PIAS3 antagonizes the repressor function of ATF1, at least in part by blocking its DNA binding, and ultimately activates the ARE. Collectively our results suggest that PIAS3 is a new regulator of ATF1 that regulates the ARE-mediated transcription of the ferritin H gene.
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MitoQ and MitoVitE exhibited a significant increase in the efficacy of cytoprotection of FRDA fibroblasts from oxidative stress-mediated toxicity when compared with Idebenone.
“Furthermore, the mitochondria-targeted antioxidants MitoQ (coenzyme Q10 derivative) and MitoVitE (vitamin E derivative) exhibited a significant increase in the efficacy of cytoprotection of FRDA fibroblasts from oxidative stress–mediated toxicity when compared with Idebenone (145).”
From Intracellular iron transport and storage: from molecular mechanisms to health implications (2008) · cites this paper as [145]
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Activating Transcription Factor 1 directs Mhem atheroprotective macrophages via coordinated Title
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- Authors
- Iwasaki, K., Hailemariam, K., & Tsuji, Y.
- Affiliations
- North Carolina State University (US)
- Corresponding author
- Tsuji, Yoshiaki
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2007-08
- Volume
- 282
- Issue
- 31
- Pages
- 22335-22343
- ISSN
- 0021-9258 (ISSN-L)
- PMC
- PMC2409283
- OpenAlex
- W2021980585
- Cited by
- 41
- References
- 72
- Citations by year
- 2024: 3 · 2023: 1 · 2020: 1 · 2019: 1 · 2016: 3 · 2015: 2 · 2014: 4 · 2013: 2 · 2012: 4
- FWCI
- 1.85
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (DK60007, R01DK060007, DK-60007S)
- National Institute of Environmental Health Sciences (ES 007046, T32ES007046)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics, phytochemicals, and oxidative stress
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- PIAS3, ATF1, antioxidant response element, transcriptional repression, SUMOylation, SUMO E3 ligase, protein-protein interaction, iron homeostasis, oxidative stress response, transcriptional regulation
- MeSH terms
- Regulatory Factor X Transcription Factors, Animals, Antioxidants, Apoferritins, DNA-Binding Proteins, Humans, Nuclear Proteins, Protein Binding, Transcription Factors, Molecular Chaperones, K562 Cells, Small Ubiquitin-Related Modifier Proteins, SUMO-1 Protein, RNA, Small Interfering, NIH 3T3 Cells, Protein Inhibitors of Activated STAT, NF-E2-Related Factor 2, Mice, Activating Transcription Factor 1
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