| First Author | Yang S | Year | 2013 |
| Journal | Nat Commun | Volume | 4 |
| Pages | 2583 | PubMed ID | 24113711 |
| Mgi Jnum | J:205986 | Mgi Id | MGI:5547630 |
| Doi | 10.1038/ncomms3583 | Citation | Yang S, et al. (2013) Pellino3 targets RIP1 and regulates the pro-apoptotic effects of TNF-alpha. Nat Commun 4:2583 |
| abstractText | Tumour necrosis factor-alpha (TNF) can activate NF-kappaB 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-kappaB 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. |
