iTAP, a novel iRhom interactor, controls TNF secretion by policing the stability of iRhom/TACE

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F18%3A00491888" target="_blank" >RIV/61388963:_____/18:00491888 - isvavai.cz</a>

Výsledek na webu

<a href="https://elifesciences.org/articles/35032" target="_blank" >https://elifesciences.org/articles/35032</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.7554/eLife.35032" target="_blank" >10.7554/eLife.35032</a>

Jazyk výsledku

angličtina

Název v původním jazyce

iTAP, a novel iRhom interactor, controls TNF secretion by policing the stability of iRhom/TACE

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

iTAP, a novel iRhom interactor, controls TNF secretion by policing the stability of iRhom/TACE

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10608 - Biochemistry and molecular biology

Projekt

<a href="/cs/project/LO1302" target="_blank" >LO1302: InterBioMed</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2018

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

eLife

ISSN

2050-084X

e-ISSN

—

Svazek periodika

7

Číslo periodika v rámci svazku

Jun 13

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

35

Strana od-do

—

Kód UT WoS článku

000438484100001

EID výsledku v databázi Scopus

2-s2.0-85051591388