ArticleMolecular and cellular biology2012
Intermolecular binding between TIFA-FHA and TIFA-pT mediates tumor necrosis factor alpha stimulation and NF-κB activation.
Article in Molecular and cellular biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 26 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
26 citing papers in PubMed, 46 citations in OpenAlex.
- TIFA: a signaling hub linking inflammation, innate immunity, and human disease.Frontiers in immunology · 2026Review
- TRAF2 binds to TIFA via a novel motif and contributes to its autophagic degradation.FEBS letters · 2025Article
- TIFAB regulates the TIFA-TRAF6 signaling pathway involved in innate immunity by forming a heterodimer complex with TIFA.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Article
- ADP-Hep-Induced Liquid Phase Condensation of TIFA-TRAF6 Activates ALPK1/TIFA-Dependent Innate Immune Responses.Research (Washington, D.C.) · 2024Article
- In vitro kinase assay reveals ADP-heptose-dependent ALPK1 autophosphorylation and altered kinase activity of disease-associated ALPK1 mutants.Scientific reports · 2023Article
- Co-ordinated control of the ADP-heptose/ALPK1 signalling network by the E3 ligases TRAF6, TRAF2/c-IAP1 and LUBAC.The Biochemical journal · 2022Article
- TIFA promotes colorectal cancer cell proliferation in an RSK- and PRAS40-dependent manner.Cancer science · 2022Article
- Review
- TIFA has dual functions in Helicobacter pylori-induced classical and alternative NF-κB pathways.EMBO reports · 2021Article
- TIFA protein expression is associated with pulmonary arterial hypertension.Scientific reports · 2021Article
- ADP-heptose: a bacterial PAMP detected by the host sensor ALPK1.Cellular and molecular life sciences : CMLS · 2021Review
- Alpk1 Sensitizes Pancreatic Beta Cells to Cytokine-Induced ApoptosisFrontiers in immunology · 2021Article
- Article
- Structural analysis of TIFA: Insight into TIFA-dependent signal transduction in innate immunity.Scientific reports · 2020Article
- TIFAB Regulates USP15-Mediated p53 Signaling during Stressed and Malignant Hematopoiesis.Cell reports · 2020Article
- XIAP controls RIPK2 signaling by preventing its deposition in speck-like structures.Life science alliance · 2019Article
- ADP-heptose is a newly identified pathogen-associated molecular pattern ofEMBO reports · 2018Article
- Article
- TRAF-interacting protein with forkhead-associated domain (TIFA) transduces DNA damage-induced activation of NF-κB.The Journal of biological chemistry · 2018Article
Corrections and comments
- Erratum issued
Authors and funding
13 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The forkhead-associated (FHA) domain recognizes phosphothreonine (pT) with high specificity and functional diversity. TIFA (TRAF-interacting protein with an FHA domain) is the smallest FHA-containing human protein. Its overexpression was previously suggested to provoke NF-κB activation, yet its exact roles in this signaling pathway and the underlying molecular mechanism remain unclear. Here we identify a novel threonine phosphorylation site on TIFA and show that this phosphorylated threonine (pT) binds with the FHA domain of TIFA, leading to TIFA oligomerization and TIFA-mediated NF-κB activation. Detailed analysis indicated that unphosphorylated TIFA exists as an intrinsic dimer and that the FHA-pT9 binding occurs between different dimers of TIFA. In addition, silencing of endogenous TIFA resulted in attenuation of tumor necrosis factor alpha (TNF-α)-mediated downstream signaling. We therefore propose that the TIFA FHA-pT9 binding provides a previously unidentified link between TNF-α stimulation and NF-κB activation. The intermolecular FHA-pT9 binding between dimers also represents a new mechanism for the FHA domain.
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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.