49 181

Cited 29 times in

TNFα induced noncanonical NF-κB activation is attenuated by RIP1 through stabilization of TRAF2.

Authors
Kim, JY; Morgan, M; Kim, DG; Lee, JY; Bai, L; Lin, Y; Liu, ZG; Kim, YS
Citation
Journal of cell science, 124(Pt 4):647-656, 2011
Journal Title
Journal of cell science
ISSN
0021-95331477-9137
Abstract
The current paradigm of noncanonical NF-κB signaling suggests that the loss of TRAF2, TRAF3 or cIAP1 and cIAP2 leads to stabilization of NF-κB-inducing kinase (NIK) to activate the noncanonical pathway. Although a crucial role of RIP1 in the TNFα-induced canonical NF-κB pathway has been well established, its involvement in noncanonical activation of NF-κB through the TNFR1 receptor, is unknown. Here we show that TNFα is capable of activating the noncanonical NF-κB 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-κB pathway through TRAF2 degradation, leading to NIK stabilization, IKKα 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 TNFα, probably as a result of lack of canonical NF-κB activation, the late activation of the noncanonical NF-κB pathway protects the remaining cells from further cell death. The TNFR1-dependent noncanonical NF-κB activation in RIP1(-/-) cells suggests that there is functional interplay between the two NF-κB pathways during TNFR1 signaling, which might regulate the number and kinds of NF-κB transcription factors and thus finely control NF-κB-dependent gene transcription.
MeSH terms
AnimalsCell LineGTPase-Activating Proteins/genetics/*metabolismHumansMiceMice, KnockoutNF-kappa B/genetics/*metabolismProtein BindingProtein StabilitySignal TransductionTNF Receptor-Associated Factor 2/chemistry/genetics/*metabolismTumor Necrosis Factor-alpha/genetics/*metabolism
DOI
10.1242/jcs.075770
PMID
21266470
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Biochemistry & Molecular Biology
AJOU Authors
김, 유선
Full Text Link
Files in This Item:
fulltext not available.txtDownload
Export
RIS (EndNote)
XLS (Excel)
XML

qrcode

해당 아이템을 이메일로 공유하기 원하시면 인증을 거치시기 바랍니다.

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse