ArticleCell reports2015
An IκB Kinase-Regulated Feedforward Circuit Prolongs Inflammation.
Article in Cell reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
What it found
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Who cites it
12 citing papers in PubMed, 15 citations in OpenAlex.
- The role of HECT-type E3 ubiquitin ligases in inflammation.Frontiers in immunology · 2026Review
- GADD45β inhibits RIPK3-mediated NF-κB activation by interfering with NEMO-RIPK1-RIPK3 interactions.Cell death discovery · 2025Article
- New Role of Protein Misfolding Corrector in the ER Stress-Inflammation Axis: Possible Therapeutic Indication in Neuronal and Epithelial Tumor Cells.International journal of molecular sciences · 2025Article
- Oxidative stress triggers Itch-mediated TXNIP degradation and NF-κB activation promoting chronic obstructive pulmonary disease.Respiratory research · 2025Article
- Natural lung-tropic TJournal for immunotherapy of cancer · 2024Article
- Acetylation, Phosphorylation, Ubiquitination (Oh My!): Following Post-Translational Modifications on the Ubiquitin Road.Biomolecules · 2022Review
- Localization of the ubiquitin ligase Dma1 to the fission yeast contractile ring is modulated by phosphorylation.FEBS letters · 2021Article
- ITCH as a potential therapeutic target in human cancers.Seminars in cancer biology · 2020Review
- The Role of Non-coding RNAs in Viral Myocarditis.Frontiers in cellular and infection microbiology · 2020Review
- Structure-Activity Relationship Studies To Identify Affinity Probes in Bis-aryl Sulfonamides That Prolong Immune Stimuli.Journal of medicinal chemistry · 2019Article
- Vinpocetine Inhibits NF-κB-Dependent Inflammation in Acute Ischemic Stroke Patients.Translational stroke research · 2018Article
- Phosphorylation of the E3 ubiquitin protein ligase ITCH diminishes binding to its cognate E2 ubiquitin ligase.The Journal of biological chemistry · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Loss of NF-κB signaling causes immunodeficiency, whereas inhibition of NF-κB can be efficacious in treating chronic inflammatory disease. Inflammatory NF-κB signaling must therefore be tightly regulated, and although many mechanisms to downregulate NF-κB have been elucidated, there have only been limited studies demonstrating positive feedforward regulation of NF-κB signaling. In this work, we use a bioinformatic and proteomic approach to discover that the IKK family of proteins can phosphorylate the E3 ubiquitin ligase ITCH, a critical downregulator of TNF-mediated NF-κB activation. Phosphorylation of ITCH by IKKs leads to impaired ITCH E3 ubiquitin ligase activity and prolongs NF-κB signaling and pro-inflammatory cytokine release. Since genetic loss of ITCH mirrors IKK-induced ITCH phosphorylation, we further show that the ITCH(-/-) mouse's spontaneous lung inflammation and subsequent death can be delayed when TNF signaling is genetically deleted. This work identifies a new positive feedforward regulation of NF-κB activation that drives inflammatory disease.
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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.