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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.
Pubmed ID: 29897333 RIS Download
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View all literature mentionsSoftware package for sequence alignment, assembly and analysis. Integrated and extendable desktop software platform for organization and analysis of sequence data. Bioinformatics software platform packed with molecular biology and sequence analysis tools.
View all literature mentionsAn Antibody supplier and subset of ThermoFisher Scientific which provides fluorescence reagents for various experiments and methods.
View all literature mentionsA quantitative proteomics software package for analyzing large-scale mass-spectrometric data sets. It is a set of algorithms that include peak detection and scoring of peptides, mass calibration, database searches for protein identification, protein quantification, and provides summary statistics.
View all literature mentionsCell line HEK293-FT is a Transformed cell line with a species of origin Homo sapiens (Human)
View all literature mentionsThis monoclonal targets HA.11
View all literature mentionsThis polyclonal targets KIAA0196
View all literature mentionsThis monoclonal targets EEA1
View all literature mentionsThis monoclonal targets LAMP2
View all literature mentionsThis polyclonal targets RCJMB04_4h19
View all literature mentionsThis recombinant monoclonal targets GAPDH
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View all literature mentionsThis monoclonal targets Transferrin Receptor
View all literature mentionsThis polyclonal targets Human FRMD8
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View all literature mentionsThis monoclonal targets Human TACE / ADAM17
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View all literature mentionsThis polyclonal targets ADAM17 - Cytoplasmic domain
View all literature mentionsCell line NCTC clone 929 is a Spontaneously immortalized cell line with a species of origin Mus musculus
View all literature mentionsCell line RAW 264.7 is a Cancer cell line with a species of origin Mus musculus
View all literature mentionsCell line HeLa is a Cancer cell line with a species of origin Homo sapiens
View all literature mentionsCell line HEK293-ET is a Transformed cell line with a species of origin Homo sapiens (Human)
View all literature mentionsMus musculus with name C57BL/6J from IMSR.
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View all literature mentionsSoftware package as distribution of ImageJ and ImageJ2 together with Java, Java3D and plugins organized into coherent menu structure. Used to assist research in life sciences.
View all literature mentionsThis polyclonal targets KIAA0196
View all literature mentionsThis monoclonal targets EEA1
View all literature mentionsThis monoclonal targets LAMP2
View all literature mentionsThis polyclonal targets RCJMB04_4h19
View all literature mentionsThis recombinant monoclonal targets GAPDH
View all literature mentionsThis monoclonal targets FLAG
View all literature mentionsThis monoclonal targets Transferrin Receptor
View all literature mentionsThis polyclonal targets Human FRMD8
View all literature mentionsThis monoclonal targets HA.11
View all literature mentionsThis monoclonal targets TUBA4A
View all literature mentionsThis monoclonal targets Human TACE / ADAM17
View all literature mentionsThis monoclonal targets p97 ATPase
View all literature mentionsThis polyclonal targets ADAM17 - Cytoplasmic domain
View all literature mentionsCell line NCTC clone 929 is a Spontaneously immortalized cell line with a species of origin Mus musculus
View all literature mentionsCell line RAW 264.7 is a Cancer cell line with a species of origin Mus musculus
View all literature mentionsCell line HeLa is a Cancer cell line with a species of origin Homo sapiens
View all literature mentionsCell line HEK293-ET is a Transformed cell line with a species of origin Homo sapiens (Human)
View all literature mentionsMus musculus with name C57BL/6J from IMSR.
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