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  Mind Bomb Regulates Cell Death during TNF Signaling by Suppressing RIPK1's Cytotoxic Potential

Feltham, R., Jamal, K., Tenev, T., Liccardi, G., Jaco, I., Domingues, C. M., et al. (2018). Mind Bomb Regulates Cell Death during TNF Signaling by Suppressing RIPK1's Cytotoxic Potential. CELL REPORTS, 23(2), 470-484. doi:10.1016/j.celrep.2018.03.054.

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Feltham, Rebecca1, Autor
Jamal, Kunzah1, Autor
Tenev, Tencho1, Autor
Liccardi, Gianmaria1, Autor
Jaco, Isabel1, Autor
Domingues, Celia Monteiro1, Autor
Morris, Otto1, Autor
John, Sidonie Wicky1, Autor
Annibaldi, Alessandro1, Autor
Widya, Marcella1, Autor
Kearney, Conor J.1, Autor
Clancy, Danielle1, Autor
Elliott, Paul R.1, Autor
Glatter, Timo2, 3, Autor                 
Qiao, Qi1, Autor
Thompson, Andrew J.1, Autor
Nesvizhskii, Alexey1, Autor
Schmidt, Alexander1, Autor
Komander, David1, Autor
Wu, Hao1, Autor
Martin, Seamus1, AutorMeier, Pascal1, Autor mehr..
Affiliations:
1external, ou_persistent22              
2Core Facility Mass Spectrometry and Proteomics, Max Planck Institute for Terrestrial Microbiology, Max Planck Society, ou_3266266              
3University of Basel, Biozentrum, Basel, Switzerland, ou_persistent22              

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 Zusammenfassung: Tumor necrosis factor (TNF) is an inflammatory cytokine that can signal cell survival or cell death. The mechanisms that switch between these distinct outcomes remain poorly defined. Here, we show that the E3 ubiquitin ligase Mind Bomb-2 (MIB2) regulates TNF-induced cell death by inactivating RIPK1 via inhibitory ubiquitylation. Although depletion of MIB2 has little effect on NF-kappa B activation, it sensitizes cells to RIPK1- and caspase-8-dependent cell death. We find that MIB2 represses the cytotoxic potential of RIPK1 by ubiquitylating lysine residues in the C-terminal portion of RIPK1. Our data suggest that ubiquitin conjugation of RIPK1 interferes with RIPK1 oligomerization and RIPK1-FADD association. Disruption of MIB2-mediated ubiquitylation, either by mutation of MIB2's E3 activity or RIPK1's ubiquitin-acceptor lysines, sensitizes cells to RIPK1-mediated cell death. Together, our findings demonstrate that Mind Bomb E3 ubiquitin ligases can function as additional checkpoint of cytokine-induced cell death, selectively protecting cells from the cytotoxic effects of TNF.

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 Datum: 2018
 Publikationsstatus: Erschienen
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 Art der Begutachtung: -
 Identifikatoren: ISI: 000429866600012
DOI: 10.1016/j.celrep.2018.03.054
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Titel: CELL REPORTS
Genre der Quelle: Zeitschrift
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Ort, Verlag, Ausgabe: -
Seiten: - Band / Heft: 23 (2) Artikelnummer: - Start- / Endseite: 470 - 484 Identifikator: ISSN: 2211-1247