ArticleThe Biochemical journal2022
Co-ordinated control of the ADP-heptose/ALPK1 signalling network by the E3 ligases TRAF6, TRAF2/c-IAP1 and LUBAC.
Article in The Biochemical journal, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
13 citing papers in PubMed, 19 citations in OpenAlex.
- Enhanced ADP-heptose-dependent NF-κB activation bymicroLife · 2026Article
- Exploring the Role of TRAF6-TAK1 Pathway in Podocyte Pyroptosis and Its Implications for Primary Membranous Nephropathy Therapy.Inflammation · 2025Article
- TRAF2 binds to TIFA via a novel motif and contributes to its autophagic degradation.FEBS letters · 2025Article
- Immune function analysis in a pediatric patient with aFrontiers in immunology · 2025Article
- Article
- Quantitative Measurement of the Kinase Activity of Wildtype ALPK1 and Disease-Causing ALPK1 Mutants Using Cell-Free Radiometric Phosphorylation Assays.Bio-protocol · 2024Article
- Measurement of the Activity of Wildtype and Disease-Causing ALPK1 Mutants in Transfected Cells With a 96-Well Format NF-κB/AP-1 Reporter Assay.Bio-protocol · 2024Article
- TIFA contributes to periodontitis in diabetic mice via activating the NF‑κB signaling pathway.Molecular medicine reports · 2024Article
- Copper regulates the host innate immune response against bacterial infection via activation of ALPK1 kinase.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- ALPK1 mutants causing ROSAH syndrome or Spiradenoma are activated by human nucleotide sugars.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- A Bittersweet Kiss of Gram-Negative Bacteria: The Role of ADP-Heptose in the Pathogenesis of Infection.Microorganisms · 2023Review
- In vitro kinase assay reveals ADP-heptose-dependent ALPK1 autophosphorylation and altered kinase activity of disease-associated ALPK1 mutants.Scientific reports · 2023Article
- From seeds to trees: how E2 enzymes grow ubiquitin chains.Biochemical Society transactions · 2023Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
ADP-heptose activates the protein kinase ALPK1 triggering TIFA phosphorylation at Thr9, the recruitment of TRAF6 and the subsequent production of inflammatory mediators. Here, we demonstrate that ADP-heptose also stimulates the formation of Lys63- and Met1-linked ubiquitin chains to activate the TAK1 and canonical IKK complexes, respectively. We further show that the E3 ligases TRAF6 and c-IAP1 operate redundantly to generate the Lys63-linked ubiquitin chains required for pathway activation, which we demonstrate are attached to TRAF6, TRAF2 and c-IAP1, and that c-IAP1 is recruited to TIFA by TRAF2. ADP-heptose also induces activation of the kinase TBK1 by a TAK1-independent mechanism, which require TRAF2 and TRAF6. We establish that ALPK1 phosphorylates TIFA directly at Thr177 as well as Thr9 in vitro. Thr177 is located within the TRAF6-binding motif and its mutation to Asp prevents TRAF6 but not TRAF2 binding, indicating a role in restricting ADP-heptose signalling. We conclude that ADP-heptose signalling is controlled by the combined actions of TRAF2/c-IAP1 and TRAF6.
Indexed as
Identifiers
What OpenQuestion holds
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.