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Poly-ubiquitination in TNFR1-mediated necroptosis

Dondelinger, Y; Darding, M; Bertrand, MJ; Walczak, H; (2016) Poly-ubiquitination in TNFR1-mediated necroptosis. Cellular Molecular Life Sciences , 73 (11) pp. 2165-2176. 10.1007/s00018-016-2191-4. Green open access

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Abstract

Tumor necrosis factor (TNF) is a master pro-inflammatory cytokine, and inappropriate TNF signaling is implicated in the pathology of many inflammatory diseases. Ligation of TNF to its receptor TNFR1 induces the transient formation of a primary membrane-bound signaling complex, known as complex I, that drives expression of pro-survival genes. Defective complex I activation results in induction of cell death, in the form of apoptosis or necroptosis. This switch occurs via internalization of complex I components and assembly and activation of secondary cytoplasmic death complexes, respectively known as complex II and necrosome. In this review, we discuss the crucial regulatory functions of ubiquitination-a post-translational protein modification consisting of the covalent attachment of ubiquitin, and multiples thereof, to target proteins-to the various steps of TNFR1 signaling leading to necroptosis.

Type: Article
Title: Poly-ubiquitination in TNFR1-mediated necroptosis
Location: Switzerland
Open access status: An open access version is available from UCL Discovery
DOI: 10.1007/s00018-016-2191-4
Publisher version: http://dx.doi.org/10.1007/s00018-016-2191-4
Language: English
Additional information: © The Author(s) 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
Keywords: A20, CYLD, LUBAC, Necroptosis, RIPK1, TNFR1, Ubiquitination, c IAP1/2
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Cancer Bio
URI: https://discovery.ucl.ac.uk/id/eprint/1485737
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