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Mind bomb regulates cell death during TNF signaling by suppressing RIPK1's cytotoxic potential

Rebecca Feltham, Kunzah Jamal, Tencho Tenev, Gianmaria Liccardi, Isabel Jaco, Celia Monteiro Domingues, Otto Morris, Sidonie Wicky John, Alessandro Annibaldi, Marcella Widya, et al.
(2018) CELL REPORTS. 23(2). p.470-484
Author
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Abstract
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.
Keywords
NF-KAPPA-B, TUMOR-NECROSIS-FACTOR, ALPHA-DEPENDENT APOPTOSIS, ACTIVATION, KINASE, RIP1, UBIQUITINATION, INFLAMMATION, CANCER, NEMO

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MLA
Feltham, Rebecca, et al. “Mind Bomb Regulates Cell Death during TNF Signaling by Suppressing RIPK1’s Cytotoxic Potential.” CELL REPORTS, vol. 23, no. 2, 2018, pp. 470–84, doi:10.1016/j.celrep.2018.03.054.
APA
Feltham, R., Jamal, K., Tenev, T., Liccardi, G., Jaco, I., Domingues, C. M., … Meier, P. (2018). Mind bomb regulates cell death during TNF signaling by suppressing RIPK1’s cytotoxic potential. CELL REPORTS, 23(2), 470–484. https://doi.org/10.1016/j.celrep.2018.03.054
Chicago author-date
Feltham, Rebecca, Kunzah Jamal, Tencho Tenev, Gianmaria Liccardi, Isabel Jaco, Celia Monteiro Domingues, Otto Morris, et al. 2018. “Mind Bomb Regulates Cell Death during TNF Signaling by Suppressing RIPK1’s Cytotoxic Potential.” CELL REPORTS 23 (2): 470–84. https://doi.org/10.1016/j.celrep.2018.03.054.
Chicago author-date (all authors)
Feltham, Rebecca, Kunzah Jamal, Tencho Tenev, Gianmaria Liccardi, Isabel Jaco, Celia Monteiro Domingues, Otto Morris, Sidonie Wicky John, Alessandro Annibaldi, Marcella Widya, Conor J. Kearney, Danielle Clancy, Paul R. Elliott, Timo Glatter, Qi Qiao, Andrew J. Thompson, Alexey Nesvizhskii, Alexander Schmidt, David Komander, Hao Wu, Seamus Martin, and Pascal Meier. 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.
Vancouver
1.
Feltham R, Jamal K, Tenev T, Liccardi G, Jaco I, Domingues CM, et al. Mind bomb regulates cell death during TNF signaling by suppressing RIPK1’s cytotoxic potential. CELL REPORTS. 2018;23(2):470–84.
IEEE
[1]
R. Feltham et al., “Mind bomb regulates cell death during TNF signaling by suppressing RIPK1’s cytotoxic potential,” CELL REPORTS, vol. 23, no. 2, pp. 470–484, 2018.
@article{8727861,
  abstract     = {{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.}},
  author       = {{Feltham, Rebecca and Jamal, Kunzah and Tenev, Tencho and Liccardi, Gianmaria and Jaco, Isabel and Domingues, Celia Monteiro and Morris, Otto and John, Sidonie Wicky and Annibaldi, Alessandro and Widya, Marcella and Kearney, Conor J. and Clancy, Danielle and Elliott, Paul R. and Glatter, Timo and Qiao, Qi and Thompson, Andrew J. and Nesvizhskii, Alexey and Schmidt, Alexander and Komander, David and Wu, Hao and Martin, Seamus and Meier, Pascal}},
  issn         = {{2211-1247}},
  journal      = {{CELL REPORTS}},
  keywords     = {{NF-KAPPA-B,TUMOR-NECROSIS-FACTOR,ALPHA-DEPENDENT APOPTOSIS,ACTIVATION,KINASE,RIP1,UBIQUITINATION,INFLAMMATION,CANCER,NEMO}},
  language     = {{eng}},
  number       = {{2}},
  pages        = {{470--484}},
  title        = {{Mind bomb regulates cell death during TNF signaling by suppressing RIPK1's cytotoxic potential}},
  url          = {{http://doi.org/10.1016/j.celrep.2018.03.054}},
  volume       = {{23}},
  year         = {{2018}},
}
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