Počet záznamů: 1
The iRhom homology domain is indispensable for ADAM17-mediated TNF alpha and EGF receptor ligand release
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SYSNO ASEP 0544132 Druh ASEP J - Článek v odborném periodiku Zařazení RIV J - Článek v odborném periodiku Poddruh J Článek ve WOS Název The iRhom homology domain is indispensable for ADAM17-mediated TNF alpha and EGF receptor ligand release Tvůrce(i) Dusterhoft, S. (DE)
Kahveci-Tuerkoez, S. (DE)
Wozniak, J. (DE)
Seifert, A. (DE)
Kašpárek, Petr (UMG-J)
Ohm, H. (DE)
Liu, S. (DE)
Kopkanová, Jana (UMG-J)
Lokau, J. (DE)
Garbers, C. (DE)
Preisinger, C. (DE)
Sedláček, Radislav (UMG-J) RID
Freeman, M. (GB)
Ludwig, A. (DE)Celkový počet autorů 14 Zdroj.dok. Cellular and Molecular Life Sciences - ISSN 1420-682X
Roč. 78, č. 11 (2021), s. 5015-5040Poč.str. 26 s. Forma vydání Online - E Jazyk dok. eng - angličtina Země vyd. CH - Švýcarsko Klíč. slova iRhom ; adam17 ; Ectodomain shedding ; tnf ; Growth factors ; iRhom homology domain Vědní obor RIV EB - Genetika a molekulární biologie Obor OECD Biochemistry and molecular biology Způsob publikování Open access Institucionální podpora UMG-J - RVO:68378050 UT WOS 000647519000003 DOI 10.1007/s00018-021-03845-3 Anotace Membrane-tethered signalling proteins such as TNF alpha and many EGF receptor ligands undergo shedding by the metalloproteinase ADAM17 to get released. The pseudoproteases iRhom1 and iRhom2 are important for the transport, maturation and activity of ADAM17. Yet, the structural and functional requirements to promote the transport of the iRhom-ADAM17 complex have not yet been thoroughly investigated. Utilising in silico and in vitro methods, we here map the conserved iRhom homology domain (IRHD) and provide first insights into its structure and function. By focusing on iRhom2, we identified different structural and functional factors within the IRHD. We found that the structural integrity of the IRHD is a key factor for ADAM17 binding. In addition, we identified a highly conserved motif within an unstructured region of the IRHD, that, when mutated, restricts the transport of the iRhom-ADAM17 complex through the secretory pathway in in vitro, ex vivo and in vivo systems and also increases the half-life of iRhom2 and ADAM17. Furthermore, the disruption of this IRHD motif was also reflected by changes in the yet undescribed interaction profile of iRhom2 with proteins involved in intracellular vesicle transport. Overall, we provide the first insights into the forward trafficking of iRhoms which is critical for TNF alpha and EGF receptor signalling. Pracoviště Ústav molekulární genetiky Kontakt Nikol Škňouřilová, nikol.sknourilova@img.cas.cz, Tel.: 241 063 217 Rok sběru 2022 Elektronická adresa https://link.springer.com/article/10.1007/s00018-021-03845-3
Počet záznamů: 1