ArticleExperimental cell research2015
Withaferin A disrupts ubiquitin-based NEMO reorganization induced by canonical NF-κB signaling.
Article in Experimental cell research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 29 citations in OpenAlex.
- NEMO/IKKγ: Emerging player in the NF-κB pathway and potential therapeutic target in inflammation.Inflammation · 2026Review
- Inhibition of NF-κB with an Analog of Withaferin-A Restores TDP-43 Homeostasis and Proteome Profiles in a Model of Sporadic ALS.Biomedicines · 2024Article
- Neuronal dysfunction caused by FUSR521G promotes ALS-associated phenotypes that are attenuated by NF-κB inhibition.Acta neuropathologica communications · 2023Article
- Withaferin A: From Ancient Remedy to Potential Drug Candidate.Molecules (Basel, Switzerland) · 2021Review
- Phosphocatalytic Kinome Activity Profiling of Apoptotic and Ferroptotic Agents in Multiple Myeloma Cells.International journal of molecular sciences · 2021Article
- Targeting TDP-43 Pathology Alleviates Cognitive and Motor Deficits Caused by Chronic Cerebral Hypoperfusion.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2021Article
- Antagonizing binding of cell cycle and apoptosis regulatory protein 1 (CARP-1) to the NEMO/IKKγ protein enhances the anticancer effect of chemotherapy.The Journal of biological chemistry · 2020Article
- Role of ashwagandha methanolic extract in the regulation of thyroid profile in hypothyroidism modeled rats.Molecular biology reports · 2019Article
- Targeting claudin-3 suppresses stem cell-like phenotype in nonsquamous non-small-cell lung carcinoma.Lung cancer management · 2019Article
- Targeting IKKβ in Cancer: Challenges and Opportunities for the Therapeutic Utilisation of IKKβ Inhibitors.Cells · 2018Review
- Withaferin A protects against spinal cord injury by inhibiting apoptosis and inflammation in mice.Pharmaceutical biology · 2017Article
- [The advances of clinical and molecular prognostic factors of diffuse large B-cell lymphoma].Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi · 2016Article
- Withaferin-A--A Natural Anticancer Agent with Pleitropic Mechanisms of Action.International journal of molecular sciences · 2016Review
- Inhibition of Canonical NF-κB Signaling by a Small Molecule Targeting NEMO-Ubiquitin Interaction.Scientific reports · 2016Article
- [Advances of aberrant signaling pathways and related targeting drugs in B cell non- Hodgkin lymphoma].Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi · 2015Article
- Targeting Cdc20 as a novel cancer therapeutic strategy.Pharmacology & therapeutics · 2015Review
- Anti-cancer activity of withaferin A in B-cell lymphoma.Cancer biology & therapy · 2015Article
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
The NF-κB family of transcription factors regulates numerous cellular processes, including cell proliferation and survival responses. The constitutive activation of NF-κB has also emerged as an important oncogenic driver in many malignancies, such as activated B-cell like diffuse large B cell lymphoma, among others. In this study, we investigated the impact and mechanisms of action of Withaferin A, a naturally produced steroidal lactone, against both signal-inducible as well as constitutive NF-κB activities. We found that Withaferin A is a robust inhibitor of canonical and constitutive NF-κB activities, leading to apoptosis of certain lymphoma lines. In the canonical pathway induced by TNF, Withaferin A did not disrupt RIP1 polyubiquitination or NEMO-IKKβ interaction and was a poor direct IKKβ inhibitor, but prevented the formation of TNF-induced NEMO foci which colocalized with TNF ligand. While GFP-NEMO efficiently formed TNF-induced foci, a GFP-NEMO(Y308S) mutant that is defective in binding to polyubiquitin chains did not form foci. Our study reveals that Withaferin A is a novel type of IKK inhibitor which acts by disrupting NEMO reorganization into ubiquitin-based signaling structures in vivo.
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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.