Article (Scientific journals)
NF-kappaB-Independent Role of IKKalpha/IKKbeta in Preventing RIPK1 Kinase-Dependent Apoptotic and Necroptotic Cell Death during TNF Signaling.
Dondelinger, Yves; Jouan-Lanhouet, Sandrine; Divert, Tatyana et al.
2015In Molecular Cell
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Abstract :
[en] TNF is a master pro-inflammatory cytokine. Activation of TNFR1 by TNF can result in both RIPK1-independent apoptosis and RIPK1 kinase-dependent apoptosis or necroptosis. These cell death outcomes are regulated by two distinct checkpoints during TNFR1 signaling. TNF-mediated NF-kappaB-dependent induction of pro-survival or anti-apoptotic molecules is a well-known late checkpoint in the pathway, protecting cells from RIPK1-independent death. On the other hand, the molecular mechanism regulating the contribution of RIPK1 to cell death is far less understood. We demonstrate here that the IKK complex phosphorylates RIPK1 at TNFR1 complex I and protects cells from RIPK1 kinase-dependent death, independent of its function in NF-kappaB activation. We provide in vitro and in vivo evidence that inhibition of IKKalpha/IKKbeta or its upstream activators sensitizes cells to death by inducing RIPK1 kinase-dependent apoptosis or necroptosis. We therefore report on an unexpected, NF-kappaB-independent role for the IKK complex in protecting cells from RIPK1-dependent death downstream of TNFR1.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Dondelinger, Yves
Jouan-Lanhouet, Sandrine
Divert, Tatyana
Théâtre, Emilie ;  Université de Liège - ULiège > GIGA-R: Laboratory of Molecular Immunology And Signal Transduction
Bertin, John
Gough, Peter J.
Giansanti, Piero
Heck, Albert J. R.
Dejardin, Emmanuel ;  Université de Liège > GIGA-R : Labo of Molecular Immunol. and Signal Transduction
Vandenabeele, Peter
Bertrand, Mathieu J. M.
Language :
English
Title :
NF-kappaB-Independent Role of IKKalpha/IKKbeta in Preventing RIPK1 Kinase-Dependent Apoptotic and Necroptotic Cell Death during TNF Signaling.
Publication date :
2015
Journal title :
Molecular Cell
ISSN :
1097-2765
eISSN :
1097-4164
Publisher :
Cell Press, United States - Massachusetts
Peer reviewed :
Peer Reviewed verified by ORBi
Commentary :
Copyright (c) 2015 Elsevier Inc. All rights reserved.
Available on ORBi :
since 10 September 2015

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