ArticleCell death & disease2016
Cereblon negatively regulates TLR4 signaling through the attenuation of ubiquitination of TRAF6.
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 38 papers.
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Who cites it
38 citing papers in PubMed, 53 citations in OpenAlex.
- Cereblon promotes influenza A virus replication through AMPK ubiquitination.Biochemistry and biophysics reports · 2026Article
- Development of Cereblon (CRBN) as an early prognostic biomarker in Paediatric Sepsis: a Prospective Observational Study Protocol.BMJ open · 2026Observational
- Safety considerations for cereblon-recruiting targeted protein degraders.Nature reviews. Drug discovery · 2026Review
- Tumor-intrinsic PD-L1 drives lung cancer progression in response to TLR stimulation by promoting autophagy through the TRAF6-BECN1 signaling axis.Experimental hematology & oncology · 2026Article
- PYCR1 drives lung cancer progression through functional interactions with EGFR and TLR signaling pathways.Experimental & molecular medicine · 2025Article
- TXNIP Suppresses Lung Cancer Progression by Inhibiting TRAF6-Mediated NF-κB Activation and Autophagy.Immune network · 2025Article
- 3-Monothiopomalidomide, a new immunomodulatory imide drug (IMiD), blunts inflammation and mitigates ischemic stroke in the rat.GeroScience · 2025Article
- β-arrestin 2 negatively regulates lung cancer progression by inhibiting the TRAF6 signaling axis for NF-κB activation and autophagy induced by TLR3 and TLR4.Cell death & disease · 2023Article
- FFAR2 antagonizes TLR2- and TLR3-induced lung cancer progression via the inhibition of AMPK-TAK1 signaling axis for the activation of NF-κB.Cell & bioscience · 2023Article
- A New Generation of IMiDs as Treatments for Neuroinflammatory and Neurodegenerative Disorders.Biomolecules · 2023Review
- Novel, thalidomide-like, non-cereblon binding drug tetrafluorobornylphthalimide mitigates inflammation and brain injury.Journal of biomedical science · 2023Article
- Article
- The Relationship Between the Expression of CRBN in Peripheral Blood and the Severity and Prognosis of Adult Sepsis.International journal of general medicine · 2023Article
- Circular RNAs in organ injury: recent development.Journal of translational medicine · 2022Review
- Cereblon Deficiency Contributes to the Development of Elastase-Induced Emphysema by Enhancing NF-κB Activation.Antioxidants (Basel, Switzerland) · 2022Article
- Activity of a Novel Anti-Inflammatory Agent F-3,6'-dithiopomalidomide as a Treatment for Traumatic Brain Injury.Biomedicines · 2022Article
- CRBN is downregulated in lung cancer and negatively regulates TLR2, 4 and 7 stimulation in lung cancer cells.Clinical and translational medicine · 2022Article
- USP15 negatively regulates lung cancer progression through the TRAF6-BECN1 signaling axis for autophagy induction.Cell death & disease · 2022Article
- Caspase-8: Friend or Foe in Bortezomib/Lenalidomide-Based Therapy for Myeloma.Frontiers in oncology · 2022Review
- Molecular Mechanisms of Cereblon-Interacting Small Molecules in Multiple Myeloma Therapy.Journal of personalized medicine · 2021Review
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cereblon (CRBN) is a substrate receptor protein for the CRL4A E3 ubiquitin ligase complex. In this study, we report on a new regulatory role of CRBN in TLR4 signaling. CRBN overexpression leads to suppression of NF-κB activation and production of pro-inflammatory cytokines including IL-6 and IL-1β in response to TLR4 stimulation. Biochemical studies revealed interactions between CRBN and TAK1, and TRAF6 proteins. The interaction between CRBN and TAK1 did not affect the association of the TAB1 and TAB2 proteins, which have pivotal roles in the activation of TAK1, whereas the CRBN-TRAF6 interaction critically affected ubiquitination of TRAF6 and TAB2. Binding mapping results revealed that CRBN interacts with the Zinc finger domain of TRAF6, which contains the ubiquitination site of TRAF6, leading to attenuation of ubiquitination of TRAF6 and TAB2. Functional studies revealed that CRBN-knockdown THP-1 cells show enhanced NF-κB activation and p65- or p50-DNA binding activities, leading to up-regulation of NF-κB-dependent gene expression and increased pro-inflammatory cytokine levels in response to TLR4 stimulation. Furthermore, Crbn(-/-) mice exhibit decreased survival in response to LPS challenge, accompanied with marked enhancement of pro-inflammatory cytokines, such as TNF-α and IL-6. Taken together, our data demonstrate that CRBN negatively regulates TLR4 signaling via attenuation of TRAF6 and TAB2 ubiquitination.
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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.