| First Author | Kim JY | Year | 2011 |
| Journal | J Cell Sci | Volume | 124 |
| Issue | Pt 4 | Pages | 647-56 |
| PubMed ID | 21266470 | Mgi Jnum | J:182877 |
| Mgi Id | MGI:5317039 | Doi | 10.1242/jcs.075770 |
| Citation | Kim JY, et al. (2011) TNFalpha induced noncanonical NF-kappaB activation is attenuated by RIP1 through stabilization of TRAF2. J Cell Sci 124(Pt 4):647-56 |
| abstractText | The current paradigm of noncanonical NF-kappaB signaling suggests that the loss of TRAF2, TRAF3 or cIAP1 and cIAP2 leads to stabilization of NF-kappaB-inducing kinase (NIK) to activate the noncanonical pathway. Although a crucial role of RIP1 in the TNFalpha-induced canonical NF-kappaB pathway has been well established, its involvement in noncanonical activation of NF-kappaB through the TNFR1 receptor, is unknown. Here we show that TNFalpha is capable of activating the noncanonical NF-kappaB pathway, but that activation of this pathway is negatively regulated by RIP1. In the absence of RIP1, TNFR1 stimulation leads to activation of the noncanonical NF-kappaB pathway through TRAF2 degradation, leading to NIK stabilization, IKKalpha phosphorylation and the processing of p100 to generate p52. Thus although RIP1(-/-) mouse embryonic fibroblasts are sensitive at early time points to cell death induced by TNFalpha, probably as a result of lack of canonical NF-kappaB activation, the late activation of the noncanonical NF-kappaB pathway protects the remaining cells from further cell death. The TNFR1-dependent noncanonical NF-kappaB activation in RIP1(-/-) cells suggests that there is functional interplay between the two NF-kappaB pathways during TNFR1 signaling, which might regulate the number and kinds of NF-kappaB transcription factors and thus finely control NF-kappaB-dependent gene transcription. |
