ArticleThe EMBO journal2004
The novel E3 ubiquitin ligase Tiul1 associates with TGIF to target Smad2 for degradation.
Article in The EMBO journal, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 88 papers.
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Who cites it
88 citing papers in PubMed, 161 citations in OpenAlex.
- Deficient chaperone-mediated autophagy drives multiorgan fibrogenesis via SMAD2/4 stabilization to sustain TGFβ-SMAD signaling.Acta pharmacologica Sinica · 2026Article
- Neuroinflammation-induced downregulation of RAB7 in murine astrocytes disrupts endo-lysosomal homeostasis and induces astrogliosis.Cell communication and signaling : CCS · 2026Article
- HECT ubiquitin ligases as regulators of inflammatory signalling.Cell death and differentiation · 2026Review
- WWP1 gain-of-function drives developmental anoikis through TGFβ pathway during neurodevelopment.Cell death discovery · 2026Article
- WW Domain-Containing E3 Ubiquitin Protein Ligase 1 (WWP1) as a Factor in Obesity-Related Metabolic Disorders: Emerging Molecular Mechanisms in Metabolic Tissues.International journal of molecular sciences · 2025Review
- Depletion of WWP1 Increases Adrb3 Expression and Lipolysis in White Adipose Tissue of Obese Mice.International journal of molecular sciences · 2025Article
- WWP1 inhibition suppresses the proliferation of pancreatic cancer cells by regulating the PI3K-AKT pathway.Journal of gastroenterology · 2025Article
- Role and therapeutic potential of the NEDD4 family in breast cancer.Frontiers in pharmacology · 2025Review
- The effects of WWP1 overexpression on the golgi apparatus stress response and proteoglycan production in adipocytes.Scientific reports · 2024Article
- A Preliminary Study on Factors That Drive Patient Variability in Human Subcutaneous Adipose Tissues.Cells · 2024Article
- TGF-β signaling in health, disease, and therapeutics.Signal transduction and targeted therapy · 2024Review
- WWP1 E3 ligase at the crossroads of health and disease.Cell death & disease · 2023Review
- Circular RNA CDR1as Mediated by Human Antigen R (HuR) Promotes Gastric Cancer Growth via miR-299-3p/TGIF1 Axis.Cancers · 2023Article
- NPRC deletion attenuates cardiac fibrosis in diabetic mice by activating PKA/PKG and inhibiting TGF-β1/Smad pathways.Science advances · 2023Article
- Systemic depletion of WWP1 improves insulin sensitivity and lowers triglyceride content in the liver of obese mice.FEBS open bio · 2023Article
- The role of NEDD4 related HECT-type E3 ubiquitin ligases in defective autophagy in cancer cells: molecular mechanisms and therapeutic perspectives.Molecular medicine (Cambridge, Mass.) · 2023Review
- The HECT family of E3 ubiquitin ligases and PTEN.Seminars in cancer biology · 2022Review
- Functional roles of E3 ubiquitin ligases in prostate cancer.Journal of molecular medicine (Berlin, Germany) · 2022Review
- Evaluation of CRISPR/Cas9 mediated TGIF gene editing to inhibit corneal fibrosis in vitro.Experimental eye research · 2022Article
- The Roles of NEDD4 Subfamily of HECT E3 Ubiquitin Ligases in Neurodevelopment and Neurodegeneration.International journal of molecular sciences · 2022Review
28 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Ubiquitin-dependent degradation plays an important role in the negative regulation of TGF-beta signaling. Here, we identify Tiul1 (for TGIF interacting ubiquitin ligase 1), a novel E3 ubiquitin ligase that inhibits TGF-beta signaling by targeting both the activated receptor and Smad2 for degradation. Tiul1 associates constitutively with Smad7 and induces degradation of the activated type I receptor without affecting the expression levels of Smad7. Tiul1 can also interact with Smad2 and the nuclear corepressor TGIF upon activation of TGF-beta signaling. Like Smad7, the steady-state levels of TGIF are not affected by Tiul1, but the interaction of Tiul1 with TGIF allows this ubiquitin ligase to target Smad2 for degradation. Consistent with this, overexpression of Tiul1 suppressed TGF-beta-induced growth arrest and transcriptional responses. In addition, silencing of Tiul1 or TGIF genes by siRNA resulted in suppression of the TGF-beta-dependent degradation of Smad2 and an enhancement of TGF-beta-mediated gene expression. These results reveal a new role for TGIF as a component of a ubiquitin ligase complex that mediates the degradation of Smad2 in response to TGF-beta signaling.
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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.