ArticleThe Journal of experimental medicine2016
Ubiquitin E3 ligase FIEL1 regulates fibrotic lung injury through SUMO-E3 ligase PIAS4.
Article in The Journal of experimental medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
What it found
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Who cites it
26 citing papers in PubMed, 37 citations in OpenAlex.
- Ubiquitin Specific Protease 9X Regulates the Activation of ARK5 and Promotes Progression of Fibrotic Remodeling.JACC. Basic to translational science · 2025Article
- Inhibition of virally induced TFEB proteasomal degradation as a host-centric therapeutic approach for coronaviral infection.Science advances · 2025Article
- Targeting E3 ubiquitin ligases: a new frontier in idiopathic pulmonary fibrosis treatment.Frontiers in immunology · 2025Review
- Post-translational modifications and bronchopulmonary dysplasia.Frontiers in pediatrics · 2024Review
- Epithelial cell invasion byVirulence · 2023Article
- The emerging roles of SUMOylation in pulmonary diseases.Molecular medicine (Cambridge, Mass.) · 2023Review
- KIAA0317 regulates SOCS1 stability to ameliorate colonic inflammation.The FEBS journal · 2023Article
- Bortezomib Inhibits Lung Fibrosis and Fibroblast Activation without Proteasome Inhibition.American journal of respiratory cell and molecular biology · 2022Article
- Disparate Interferon Signaling and Shared Aberrant Basaloid Cells in Single-Cell Profiling of Idiopathic Pulmonary Fibrosis and Systemic Sclerosis-Associated Interstitial Lung Disease.Frontiers in immunology · 2021Article
- A small molecule NRF2 activator BC-1901S ameliorates inflammation through DCAF1/NRF2 axis.Redox biology · 2020Article
- Kelch-like protein 42 is a profibrotic ubiquitin E3 ligase involved in systemic sclerosis.The Journal of biological chemistry · 2020Article
- The RNFT2/IL-3Rα axis regulates IL-3 signaling and innate immunity.JCI insight · 2020Article
- The RING-type E3 ligase RNF186 ubiquitinates Sestrin-2 and thereby controls nutrient sensing.The Journal of biological chemistry · 2019Article
- Perturbation of maternal PIASy abundance disrupts zygotic genome activation and embryonic development via SUMOylation pathway.Biology open · 2019Article
- KIAA0317 regulates pulmonary inflammation through SOCS2 degradation.JCI insight · 2019Article
- Different SUMO paralogues determine the fate of wild-type and mutant CFTRs: biogenesis versus degradation.Molecular biology of the cell · 2019Article
- The ubiquitin proteasome system as a potential therapeutic target for systemic sclerosis.Translational research : the journal of laboratory and clinical medicine · 2018Review
- Ubiquitination and deubiquitination emerge as players in idiopathic pulmonary fibrosis pathogenesis and treatment.JCI insight · 2018Review
- Ubiquitination in Scleroderma Fibrosis and Its Treatment.Frontiers in immunology · 2018Review
- RING finger protein 113A regulates C-X-C chemokine receptor type 4 stability and signaling.American journal of physiology. Cell physiology · 2017Article
Corrections and comments
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
The E3 small ubiquitin-like modifier (SUMO) protein ligase protein inhibitor of activated STAT 4 (PIAS4) is a pivotal protein in regulating the TGFβ pathway. In this study, we discovered a new protein isoform encoded by KIAA0317, termed fibrosis-inducing E3 ligase 1 (FIEL1), which potently stimulates the TGFβ signaling pathway through the site-specific ubiquitination of PIAS4. FIEL1 targets PIAS4 using a double locking mechanism that is facilitated by the kinases PKCζ and GSK3β. Specifically, PKCζ phosphorylation of PIAS4 and GSK3β phosphorylation of FIEL1 are both essential for the degradation of PIAS4. FIEL1 protein is highly expressed in lung tissues from patients with idiopathic pulmonary fibrosis (IPF), whereas PIAS4 protein levels are significantly reduced. FIEL1 overexpression significantly increases fibrosis in a bleomycin murine model, whereas FIEL1 knockdown attenuates fibrotic conditions. Further, we developed a first-in-class small molecule inhibitor toward FIEL1 that is highly effective in ameliorating fibrosis in mice. This study provides a basis for IPF therapeutic intervention by modulating PIAS4 protein abundance.
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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.