ArticleCell death & disease2016
De-ubiquitinating enzyme, USP11, promotes transforming growth factor β-1 signaling through stabilization of transforming growth factor β receptor II.
Article in Cell death & disease, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 63 citations in OpenAlex.
- Ubiquitin-specific protease 11 facilitates the activation and proliferation of renal interstitial fibroblasts through epidermal growth factor receptor signaling pathways.Renal failure · 2026Article
- X-Linked USP11 Drives Depression-Like Behaviors by Stabilizing CK2α and Disrupting Mitochondrial Function.CNS neuroscience & therapeutics · 2026Article
- The Ubiquitin-Specific Protease Family: Master Regulators of Renal Fibrosis Pathogenesis and Therapeutic Targets.International journal of molecular sciences · 2026Review
- Targeting ubiquitination in disease and therapy.Signal transduction and targeted therapy · 2025Review
- Lactate orchestrates the TGFβ pathway and ferroptosis nexus in organ fibrosis via USP2 lactylation.Communications biology · 2025Article
- IL27RA promotes the proliferation and metastasis of hepatocellular carcinoma cells by regulating TGFβR1.Scientific reports · 2025Article
- The USP11/TCEAL1 complex promotes transcription elongation to sustain oncogenic gene expression in neuroblastoma.Genes & development · 2025Article
- Loss of Ubiquitin-Specific Protease 11 Mitigates Pulmonary Fibrosis in Human Pluripotent Stem Cell-Derived Alveolar Organoids.International journal of stem cells · 2025Article
- Ubiquitin specific peptidase 11 knockdown slows Huntington's disease progression via regulating mitochondrial dysfunction and neuronal damage depending on PTEN-mediated AKT pathway.Molecular medicine (Cambridge, Mass.) · 2025Article
- Inhibition of USP11 attenuates sepsis-associated acute kidney injury by downregulating TGFBR2/Smad3 signaling.Frontiers in molecular biosciences · 2025Article
- Targeting USP11 counteractsTheranostics · 2025Article
- The deubiquitinating enzyme USP11 regulates breast cancer progression by stabilizing PGAM5.Breast cancer research : BCR · 2024Article
- TGF‑β/Smad signaling in chronic kidney disease: Exploring post‑translational regulatory perspectives (Review).Molecular medicine reports · 2024Review
- Integrative and comprehensive pan-cancer analysis of ubiquitin specific peptidase 11 (Heliyon · 2024Article
- Demethyleneberberine Alleviates Pulmonary Fibrosis through Disruption of USP11 Deubiquitinating GREM1.Pharmaceuticals (Basel, Switzerland) · 2024Article
- circGRHPR inhibits aberrant epithelial-mesenchymal transformation progression of lung epithelial cells associated with idiopathic pulmonary fibrosis.Cell biology and toxicology · 2024Article
- USP11 potentiates HGF/AKT signaling and drives metastasis in hepatocellular carcinoma.Oncogene · 2024Article
- Article
- The lysine methyltransferase SMYD5 amplifies HIV-1 transcription and is post-transcriptionally upregulated by Tat and USP11.Cell reports · 2023Article
- Deubiquitinating enzyme USP11 promotes renal tubular cell senescence and fibrosis via inhibiting the ubiquitin degradation of TGF-β receptor II.Acta pharmacologica Sinica · 2023Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
The transforming growth factor β-1 (TGFβ-1) signaling pathway plays a central role in the pathogenesis of pulmonary fibrosis. Two TGFβ-1 receptors, TβRI and TβRII, mediate this pathway. TβRI protein stability, as mediated by the ubiquitin/de-ubiquitination system, has been well studied; however, the molecular regulation of TβRII still remains unclear. Here we reveal that a de-ubiquitinating enzyme, USP11, promotes TGFβ-1 signaling through de-ubiquitination and stabilization of TβRII. We elucidate the role that mitoxantrone (MTX), an USP11 inhibitor, has in the attenuation of TGFβ-1 signaling. Inhibition or downregulation of USP11 results in increases in TβRII ubiquitination and reduction of TβRII stability. Subsequently, TGFβ-1 signaling is greatly attenuated, as shown by the decreases in phosphorylation of SMAD2/3 levels as well as that of fibronectin (FN) and smooth muscle actin (SMA). Overexpression of USP11 reduces TβRII ubiquitination and increases TβRII stabilization, thereby elevating phosphorylation of SMAD2/3 and the ultimate expression of FN and SMA. Further, elevated expression of USP11 and TβRII were detected in lung tissues from bleomycin-challenged mice and IPF patients. Therefore, USP11 may contribute to the pathogenesis of pulmonary fibrosis by stabilization of TβRII and promotion of TGFβ-1 signaling. This study provides mechanistic evidence for development of USP11 inhibitors as potential antifibrotic drugs for pulmonary fibrosis.
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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.