ArticleThe Journal of biological chemistry2006
Regulation of the ring finger E3 ligase Siah2 by p38 MAPK.
Article in The Journal of biological chemistry, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
44 citing papers in PubMed, 83 citations in OpenAlex.
- Targeting PPARγ via SIAH1/2-mediated ubiquitin-proteasomal degradation as a new therapeutic approach in luminal-type bladder cancer.Cell death & disease · 2024Article
- SIAH2 regulates DNA end resection and replication fork recovery by promoting CtIP ubiquitination.Nucleic acids research · 2022Article
- Article
- Self-Sustained Regulation or Self-Perpetuating Dysregulation: ROS-dependent HIF-YAP-Notch Signaling as a Double-Edged Sword on Stem Cell Physiology and Tumorigenesis.Frontiers in cell and developmental biology · 2022Review
- Chronic and Cycling Hypoxia: Drivers of Cancer Chronic Inflammation through HIF-1 and NF-κB Activation: A Review of the Molecular Mechanisms.International journal of molecular sciences · 2021Review
- Ubiquitin-related processes and innate immunity in C. elegans.Cellular and molecular life sciences : CMLS · 2021Review
- E3 ubiquitin ligase-mediated regulation of vertebrate ocular development; new insights into the function of SIAH enzymes.Biochemical Society transactions · 2021Review
- Helicobacter pylori-induced gastric cancer is orchestrated by MRCKβ-mediated Siah2 phosphorylation.Journal of biomedical science · 2021Article
- Regulation of the SIAH2-HIF-1 Axis by Protein Kinases and Its Implication in Cancer Therapy.Frontiers in cell and developmental biology · 2021Review
- Nuclear P38: Roles in Physiological and Pathological Processes and Regulation of Nuclear Translocation.International journal of molecular sciences · 2020Review
- Vav1 is Essential for HIF-1α Activation via a Lysosomal VEGFR1-Mediated Degradation Mechanism in Endothelial Cells.Cancers · 2020Article
- Siah2 control of T-regulatory cells limits anti-tumor immunity.Nature communications · 2020Article
- Genome-Wide Identification of Apple Ubiquitin SINA E3 Ligase and Functional Characterization of MdSINA2.Frontiers in plant science · 2020Article
- An overview of mammalian p38 mitogen-activated protein kinases, central regulators of cell stress and receptor signaling.F1000Research · 2020Review
- Phosphorylation of Arabidopsis SINA2 by CDKG1 affects its ubiquitin ligase activity.BMC plant biology · 2018Article
- Ubiquitin ligases in oncogenic transformation and cancer therapy.Nature reviews. Cancer · 2018Review
- The p38 pathway, a major pleiotropic cascade that transduces stress and metastatic signals in endothelial cells.Oncotarget · 2017Review
- MiR-30 Family Potentially Targeting PI3K-SIAH2 Predicted Interaction Network Represents a Novel Putative Theranostic Panel in Non-small Cell Lung Cancer.Frontiers in genetics · 2017Article
- Seven in Absentia E3 Ubiquitin Ligases: Central Regulators of Neural Cell Fate and Neuronal Polarity.Frontiers in cellular neuroscience · 2017Review
- Editorial: Cancer Diagnostic and Therapeutic Target Identification and Verification Based on the Regulatory Functions of MicroRNAs.Frontiers in genetics · 2017Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
The RING finger ubiquitin ligase Siah2 controls the stability of various substrates involved in stress and hypoxia responses, including the PHD3, which controls the stability of HIF-1alpha. In the present study we determined the role of Siah2 phosphorylation in the regulation of its activity toward PHD3. We show that Siah2 is subject to phosphorylation by p38 MAPK, which increases Siah2-mediated degradation of PHD3. Consistent with these findings, MKK3/MKK6 double-deficient cells, which cannot activate p38 kinases, exhibit impaired Siah2-dependent degradation of PHD3. Phosphopeptide mapping identified T24 and S29 as the primary phospho-acceptor sites. Phospho-mutant forms of Siah2 (S29A or T24A/S29A) exhibit impaired degradation of PHD3, particularly after hypoxia. Conversely, a phospho-mimic form of Siah2 (T24E/S29D) exhibits stronger degradation of PHD3, compared with wild type Siah2. Whereas phospho-mutant Siah2 exhibits weaker association with PHD3, phospho-mimic Siah2 associates as well as wild type and is localized within the perinuclear region, suggesting that phosphorylation of Siah2 affects its subcellular localization and, consequently, the degree of its association with PHD3. In all, our findings reveal the phosphorylation of Siah2 by p38 and the implications of such phosphorylation for Siah2 activity toward PHD3.
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Registered trials
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.