ArticleScientific reports2017
E3 ubiquitin ligase Nedd4 inhibits AP-1 activity and TNF-α production through targeting p38α for polyubiquitination and subsequent degradation.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 24 citations in OpenAlex.
- The role of NEDD4-mediated ubiquitination of AQP5 in allergic rhinitis: implications for nasal mucosal barrier function.Frontiers in immunology · 2026Article
- Targeting TTK Inhibits Tumorigenesis of T-Cell Lymphoma Through Dephosphorylating p38α and Activating AMPK/mTOR Pathway.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- NEDD4 lactylation promotes APAP induced liver injury through Caspase11 dependent non-canonical pyroptosis.International journal of biological sciences · 2024Article
- Reprogramming of tumor-associated macrophages via NEDD4-mediated CSF1R degradation by targeting USP18.Cell reports · 2023Article
- Synthesis,Journal of enzyme inhibition and medicinal chemistry · 2023Article
- NEDD4-1 deficiency impairs satellite cell function during skeletal muscle regeneration.Biological research · 2023Article
- NEDD4 attenuates oxidized low‑density lipoprotein‑induced inflammation and dysfunction in vascular endothelial cells via regulating APEX1 expression.Experimental and therapeutic medicine · 2023Article
- Samotolisib Attenuates Acute Liver Injury Through Inhibiting Caspase-11-Mediated Pyroptosis Via Regulating E3 Ubiquitin Ligase Nedd4.Frontiers in pharmacology · 2021Article
- Multi-Omic Data Integration Allows Baseline Immune Signatures to Predict Hepatitis B Vaccine Response in a Small Cohort.Frontiers in immunology · 2020Observational
- Phosphorylated MAPK14 Promotes the Proliferation and Migration of Bladder Cancer Cells by Maintaining RUNX2 Protein Abundance.Cancer management and research · 2020Article
- E3 ubiquitin ligase Nedd4 is a key negative regulator for non-canonical inflammasome activation.Cell death and differentiation · 2019Article
- Regulation of Krüppel-like factor 8 by the NEDD4 E3 ubiquitin ligase.American journal of translational research · 2019Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
p38α plays an important role in many inflammatory diseases, such as skin inflammation, endotoxic shock and arthritis. Ubiquitination is a vital posttranslational modification of proteins and plays a crucial regulatory role in inflammatory cells. It has been reported that ubiquitination of Tak1 and TAB1 upstream of p38α can regulate p38α activation respectively. However, p38α ubiquitination is not yet clear. In this paper, we showed that E3 ubiquitin ligase Nedd4 is a regulatory component of the p38α pathway and is responsible for polyubiquitination of p38α through K48-linked and K63-linked polyubiquitination. The levels of p38α and its downstream target TNF-α were increased in Nedd4 deficient macrophages response to LPS compared with wild-type cells. AP-1 activity and degradation of p38α were induced by Nedd4 in a dose-dependent manner. Furthermore, we found that phosphorylation of p38α is involved in the interactions between p38α and Nedd4 and subsequently promotes polyubiquitination of p38α, especially K48-linked polyubiquitination by Nedd4. The different conformation of two p38α isoforms (p38αV1 and p38αV2) might be the cause of their different interactions with Nedd4 and their polyubiquitination sites by Nedd4. Thus, NEDD4 is a previously unknown component of the p38α signaling complex necessary for TNF-α activation.
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