ArticleeLife2018
iTAP, a novel iRhom interactor, controls TNF secretion by policing the stability of iRhom/TACE.
Article in eLife, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 85 citations in OpenAlex.
- ADAM17 and its proteolytic targets in disease pathogenesis.The FEBS journal · 2026Review
- Transferrin receptor 1 shedding by the pro-inflammatory iRhom-ADAM17 complex and ADAM10 regulates cellular iron uptake and ferroptosis.Experimental & molecular medicine · 2026Article
- Structural basis for ADAM17 activation by the iRhom1 pseudoprotease.Cell reports · 2026Article
- Immunomagnetic Sample Preparation Targeting Host- and Viral-Derived Antigens for HIV-1 Isolation from Limited Plasma Volumes.Analytical chemistry · 2026Article
- A sterol-binding pocket in iRhom1 underlies paralog-specific regulation of the sheddase ADAM17.bioRxiv : the preprint server for biology · 2026Article
- Chromatin dynamics identifies 78 genes at loci associated with elevated intraocular pressure and primary open-angle glaucoma.bioRxiv : the preprint server for biology · 2026Article
- ADAM17 as a proteolytic rheostat linking inflammation, tissue repair, and failure of inflammatory resolution in liver injury and fibrosis.Frontiers in pharmacology · 2026Review
- FRMD8 inhibits tumor metastasis in BRCA1-associated TNBC by negatively regulating tmTNF-α.Cellular & molecular biology letters · 2025Article
- Structural insights into the activation and inhibition of the ADAM17-iRhom2 complex.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Loss function of tumor suppressor FRMD8 confers resistance to tamoxifen therapy via a dual mechanism.eLife · 2025Article
- Whole exome sequencing analyses identified novel genes for Alzheimer's disease and related dementia.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- Whole exome sequencing analyses identified novel genes for Alzheimer's disease and related dementia.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- Lung Cancer and Interstitial Lung Diseases.Cancers · 2024Review
- Role of iRhom2 in Olfaction: Implications for Odorant Receptor Regulation and Activity-Dependent Adaptation.International journal of molecular sciences · 2024Article
- LINC01002 functions as a ceRNA to regulate FRMD8 by sponging miR-4324 for the development of COVID-19.Virology journal · 2024Article
- iRhom2 regulates ectodomain shedding and surface expression of the major histocompatibility complex (MHC) class I.Cellular and molecular life sciences : CMLS · 2024Article
- Pathological mutations reveal the key role of the cytosolic iRhom2 N-terminus for phosphorylation-independent 14-3-3 interaction and ADAM17 binding, stability, and activity.Cellular and molecular life sciences : CMLS · 2024Article
- Pentapeptide PYRAE triggers ER stress-mediated apoptosis of breast cancer cells in mice by targeting RHBDF1-BiP interaction.Acta pharmacologica Sinica · 2024Article
- Cleavage of the pseudoprotease iRhom2 by the signal peptidase complex reveals an ER-to-nucleus signaling pathway.Molecular cell · 2024Article
- Palmitoyltransferase ZDHHC3 Aggravates Nonalcoholic Steatohepatitis by Targeting S-Palmitoylated IRHOM2.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
Corrections and comments
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Authors and funding
17 authors at 6 institutions in 7 countries.
Funding
Abstract
The apical inflammatory cytokine TNF regulates numerous important biological processes including inflammation and cell death, and drives inflammatory diseases. TNF secretion requires TACE (also called ADAM17), which cleaves TNF from its transmembrane tether. The trafficking of TACE to the cell surface, and stimulation of its proteolytic activity, depends on membrane proteins, called iRhoms. To delineate how the TNF/TACE/iRhom axis is regulated, we performed an immunoprecipitation/mass spectrometry screen to identify iRhom-binding proteins. This identified a novel protein, that we name iTAP (iRhom Tail-Associated Protein) that binds to iRhoms, enhancing the cell surface stability of iRhoms and TACE, preventing their degradation in lysosomes. Depleting iTAP in primary human macrophages profoundly impaired TNF production and tissues from iTAP KO mice exhibit a pronounced depletion in active TACE levels. Our work identifies iTAP as a physiological regulator of TNF signalling and a novel target for the control of inflammation.
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