ArticleThe Journal of biological chemistry2012
Polyubiquitination of transforming growth factor β (TGFβ)-associated kinase 1 mediates nuclear factor-κB activation in response to different inflammatory stimuli.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 65 citations in OpenAlex.
- Trial
- SARS-CoV-2 Nsp1 suppresses the canonical NF-κB pathway by promoting ubiquitin-dependent degradation of TAK1 kinase.PLoS pathogens · 2026Article
- Targeted Therapy and Immunotherapies in Hepatocellular Carcinoma: Mechanisms and Clinical Studies.MedComm · 2026Review
- The effect of CD40 agonist antibody therapy on the pancreatic cancer microenvironment.Naunyn-Schmiedeberg's archives of pharmacology · 2026Review
- APIP regulates the priming of canonical NLRP3 and non-canonical Caspase-11/4 inflammasomes by binding to TRAF6.Nature communications · 2025Article
- Epigenetic regulatory protein chromobox family regulates multiple signalling pathways and mechanisms in cancer.Clinical epigenetics · 2025Review
- The TβRI promotes migration and metastasis through thrombospondin 1 and ITGAV in prostate cancer cells.Oncogene · 2024Article
- TGF-β signaling in health, disease, and therapeutics.Signal transduction and targeted therapy · 2024Review
- Bibliometric and visualized analysis on global trends and hotspots of TAK1 in regulated cell death: 1999 to 2024.Frontiers in immunology · 2024Article
- Targeting transforming growth factor beta signaling in metastatic osteosarcoma.Journal of bone oncology · 2023Review
- Black Tea Extract, via Modulation of TGF-β Pathway, Prevents Inorganic Arsenic-induced Development of Squamous Cell Carcinoma of the Skin in Swiss Albino Mice.Journal of cancer prevention · 2023Article
- Inhibitory effects of fluoxetine on the secretion of inflammatory mediators and JAK/STAT3 and JNK/TLR4 gene expression.Molecular biology reports · 2023Article
- Review
- Dysregulation of the immune response in TGF-β signalopathies.Frontiers in immunology · 2022Review
- The deubiquitinase OTUB1 augments NF-κB-dependent immune responses in dendritic cells in infection and inflammation by stabilizing UBC13.Cellular & molecular immunology · 2021Article
- Challenges and Opportunities for Drug Repositioning in Fibrodysplasia Ossificans Progressiva.Biomedicines · 2021Review
- Post-Translational Modifications That Drive Prostate Cancer Progression.Biomolecules · 2021Review
- TAK1: A Molecular Link Between Liver Inflammation, Fibrosis, Steatosis, and Carcinogenesis.Frontiers in cell and developmental biology · 2021Review
- WAVE3 phosphorylation regulates the interplay between PI3K, TGF-β, and EGF signaling pathways in breast cancer.Oncogenesis · 2020Article
- TGF-β Signaling.Biomolecules · 2020Review
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The transcription factor nuclear factor κB (NF-κB) plays a central role in regulating inflammation in response to several external signals. The TGFβ-associated kinase 1 (TAK1) is an upstream regulator of NF-κB signaling. In TGFβ-stimulated cells, TAK1 undergoes Lys-63-linked polyubiquitination at Lys-34 by TNF receptor-associated factor 6 and is thereby activated. The aim of this study was to investigate whether TAK1 polyubiquitination at Lys-34 is also essential for NF-κB activation via TNF receptor, IL-1 receptor and toll-like receptor 4. We observed that TAK1 polyubiquitination occurred at Lys-34 and required the E3 ubiquitin ligase TNF receptor-associated factor 6 after stimulation of cells with IL-1β. Polyubiquitination of TAK1 also occurred at Lys-34 in cells stimulated by TNF-α and LPS, which activates TLR4, as well as in HepG2 and prostate cancer cells stimulated with TGFβ, which in all cases resulted in NF-κB activation. Expression of a K34R-mutant TAK1 led to a reduced NF-κB activation, IL-6 promoter activity, and proinflammatory cytokine secretion by TNF-α-stimulated PC-3U cells. Similar results were obtained in the mouse macrophage cell line RAW264.7 after LPS treatment. In conclusion, polyubiquitination of TAK1 is correlated with activation of TAK1 and is essential for activation of NF-κB signaling downstream of several receptors.
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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.