ArticleThe Journal of biological chemistry2013
Seven in absentia homolog 2 (Siah2) protein is a regulator of NF-E2-related factor 2 (Nrf2).
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 56 citations in OpenAlex.
- Repurposing statins for choriocarcinoma: targeting the mevalonate pathway to disrupt mechanosignaling and overcome therapeutic resistance.Clinical & experimental metastasis · 2026Review
- Unravelling Ferroptosis in Sepsis: A Comprehensive Integrative Transcriptomic Analysis Across Age and Disease Severity.Bioinformatics and biology insights · 2026Article
- Okanin Suppresses the Growth of Colorectal Cancer Cells by Targeting at Peroxiredoxin 5.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- NRF2 Dysregulation and Therapeutic Insights Across Chronic Kidney Diseases.International journal of molecular sciences · 2025Review
- Regio- and Stereoselective Synthesis of Nitro-fatty Acids as NRF2 Pathway Activators Working under Ambient or Hypoxic Conditions.Journal of medicinal chemistry · 2025Article
- How to deal with frenemy NRF2: Targeting NRF2 for chemoprevention and cancer therapy.Journal of food and drug analysis · 2023Review
- Genistein and Procyanidin B2 Reduce Carcinogen-Induced Reactive Oxygen Species and DNA Damage through the Activation of Nrf2/ARE Cell Signaling in Bronchial Epithelial Cells In Vitro.International journal of molecular sciences · 2023Article
- Nrf2 and Parkin-Hsc70 regulate the expression and protein stability of p62/SQSTM1 under hypoxia.Scientific reports · 2022Article
- NRF2 and Diabetes: The Good, the Bad, and the Complex.Diabetes · 2022Review
- Soy Isoflavones Protect Neuronal PC12 Cells against Hypoxic Damage through Nrf2 Activation and Suppression of p38 MAPK and AKT-mTOR Pathways.Antioxidants (Basel, Switzerland) · 2022Article
- Siah2-GRP78 interaction regulates ROS and provides a proliferative advantage to Helicobacter pylori-infected gastric epithelial cancer cells.Cellular and molecular life sciences : CMLS · 2022Article
- Targeting Ferroptosis by Ubiquitin System Enzymes: A Potential Therapeutic Strategy in Cancer.International journal of biological sciences · 2022Review
- Impaired antioxidant KEAP1-NRF2 system in amyotrophic lateral sclerosis: NRF2 activation as a potential therapeutic strategy.Molecular neurodegeneration · 2021Review
- Nrf2 mediates hypoxia-inducible HIF1α activation in kidney tubular epithelial cells.American journal of physiology. Renal physiology · 2021Article
- Regulation of the SIAH2-HIF-1 Axis by Protein Kinases and Its Implication in Cancer Therapy.Frontiers in cell and developmental biology · 2021Review
- SIAH2-mediated and organ-specific restriction of HO-1 expression by a dual mechanism.Scientific reports · 2020Article
- Progressive Rotavirus Infection Downregulates Redox-Sensitive Transcription Factor Nrf2 and Nrf2-Driven Transcription Units.Oxidative medicine and cellular longevity · 2020Article
- Bovine Herpesvirus 1 Productive Infection Led to Inactivation of Nrf2 Signaling through Diverse Approaches.Oxidative medicine and cellular longevity · 2019Article
- PML-Nuclear Bodies Regulate the Stability of the Fusion Protein Dendra2-Nrf2 in the Nucleus.Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology · 2018Article
- Effects of acute hypoxia exposure with different durations on activation of Nrf2-ARE pathway in mouse skeletal muscle.PloS one · 2018Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Under pathological conditions such as ischemia-reperfusion, Nrf2 acts as a key regulator of cellular oxidative response. Provided that Nrf2 is sensitive to hypoxia during ischemia, Nrf2 may affect reactive oxygen species metabolism during reoxygenation. In this study, hypoxia suppressed Nrf2 protein, and its hypoxic suppression was not recovered with knockdown of the Nrf2 repressor Keap1. Moreover, an Nrf2 mutant lacking the Keap1 binding domain was suppressed under hypoxia, suggesting that Keap1 does not contribute to hypoxic Nrf2 suppression. HIF-1α and Siah2 are both key regulators of hypoxic responses. Hypoxia induced the Siah2 protein. Although inhibition or knockdown of Siah2 prevented the suppression of Nrf2, knockdown of HIF-1α did not. Moreover, Siah2 interacted with Nrf2 through a binding motif, suggesting that Siah2 contributes to the suppression of Nrf2. Some cytosolic kinases also play important roles in Nrf2 regulation. In this study, PKC phosphorylates serine residues of Nrf2 during hypoxia. Knockdown of Siah2 rescued hypoxic decreases in an Nrf2 mutant that mimicked phosphorylation at serine 40 or lacked this phosphorylation site, suggesting that Siah2 contributes to the degradation of Nrf2 irrespective of its phosphorylation status. Moreover, knockdown of Siah2 attenuated ubiquitination of the Nrf2 mutant, suggesting that association of Siah2 with Nrf2 causes proteasome-mediated degradation of Nrf2.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.