ArticlePLoS genetics2014
Loss of Trabid, a new negative regulator of the drosophila immune-deficiency pathway at the level of TAK1, reduces life span.
Article in PLoS genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 63 citations in OpenAlex.
- Tracheal terminal cells ofeLife · 2026Article
- IbinA and IbinB regulate the Toll pathway-mediated immune response in Drosophila melanogaster.BMC biology · 2026Article
- Resource reallocation under persistent immune activation drives trade-offs between life history and immunity in pirk-deficient Musca domestica.BMC biology · 2025Article
- Aging and diet alter the protein ubiquitylation landscape in the mouse brain.Nature communications · 2025Article
- Chronic airway inflammation inFrontiers in immunology · 2025Article
- Neuronal expressions of Taxi and Adar are crucial in maintaining the lifespan ofJournal of genetics · 2025Article
- Drosophila eIF3f1 mediates host immune defense by targeting dTak1.EMBO reports · 2024Article
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- The Intestinal Immune Defense System in Insects.International journal of molecular sciences · 2022Review
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- Dynamic Regulation of NF-κB Response in Innate Immunity: The Case of the IMD Pathway in Drosophila.Biomedicines · 2022Review
- Endoplasmic reticulum-associated protein degradation contributes to Toll innate immune defense inFrontiers in immunology · 2022Article
- A Feedback Regulatory Loop Involving dTrbd/dTak1 in Controlling IMD Signaling inFrontiers in immunology · 2022Article
- KPI5 Is Involved in the Regulation of the Expression of Antibacterial Peptide Genes and Hemolymph Melanization in the Silkworm,Frontiers in immunology · 2022Article
- Aspirin Positively Contributes toAging and disease · 2021Article
- Protein Phosphatase 4 Negatively Regulates the Immune Deficiency-NF-κB Pathway during theJournal of immunology (Baltimore, Md. : 1950) · 2021Article
- Disparate regulation of IMD signaling drives sex differences in infection pathology inProceedings of the National Academy of Sciences of the United States of America · 2021Article
- Verloren negatively regulates the expression of IMD pathway dependent antimicrobial peptides in Drosophila.Scientific reports · 2021Article
- Functional conservation in genes and pathways linking ageing and immunity.Immunity & ageing : I & A · 2021Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
A relatively unexplored nexus in Drosophila Immune deficiency (IMD) pathway is TGF-beta Activating Kinase 1 (TAK1), which triggers both immunity and apoptosis. In a cell culture screen, we identified that Lysine at position 142 was a K63-linked Ubiquitin acceptor site for TAK1, required for signalling. Moreover, Lysine at position 156 functioned as a K48-linked Ubiquitin acceptor site, also necessary for TAK1 activity. The deubiquitinase Trabid interacted with TAK1, reducing immune signalling output and K63-linked ubiquitination. The three tandem Npl4 Zinc Fingers and the catalytic Cysteine at position 518 were required for Trabid activity. Flies deficient for Trabid had a reduced life span due to chronic activation of IMD both systemically as well as in their gut where homeostasis was disrupted. The TAK1-associated Binding Protein 2 (TAB2) was linked with the TAK1-Trabid interaction through its Zinc finger domain that pacified the TAK1 signal. These results indicate an elaborate and multi-tiered mechanism for regulating TAK1 activity and modulating its immune signal.
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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.