Pellino3 targets RIP1 and regulates the pro-apoptotic effects of TNF-α


Yang, Shuo and Wang, Bingwei and Tang, Lisa S. and Siednienko, Jackub and Callanan, John J. and Moynagh, Paul N. (2013) Pellino3 targets RIP1 and regulates the pro-apoptotic effects of TNF-α. Nature Communications, 4 (2583). ISSN 2041-1723

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Abstract

Tumour necrosis factor-α (TNF) can activate NF-κB to induce pro-inflammatory genes but can also stimulate the caspase cascade to promote apoptosis. Here we show that deficiency of the ubiquitin E3 ligase, Pellino3, sensitizes cells to TNF-induced apoptosis without inhibiting the NF-κB pathway. Suppressed expression of Pellino3 leads to enhanced formation of the death-induced signalling complex, complex II, in response to TNF. We show that Pellino3 targets RIP1, in a TNF-dependent manner, to inhibit TNF-induced complex II formation and caspase 8-mediated cleavage of RIP1 in response to TNF/cycloheximide co-stimulation. Pellino3-deficient mice also show increased sensitivity to TNF-induced apoptosis and greatly increased lethality in response to TNF administration. These findings define Pellino3 as a novel regulator of TNF signalling and an important determining factor in dictating whether TNF induces cell survival or death.

Item Type: Article
Keywords: Pellino3 targets; RIP1; pro-apoptotic effects; TNF-α;
Academic Unit: Faculty of Science and Engineering > Biology
Faculty of Science and Engineering > Research Institutes > Institute of Immunology
Item ID: 8126
Identification Number: 10.1038/ncomms3583
Depositing User: Professor Paul Moynagh
Date Deposited: 05 Apr 2017 15:55
Journal or Publication Title: Nature Communications
Publisher: Nature Publshing Group
Refereed: Yes
URI:

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