TY  - JOUR
A1  - Diamanti, Michaela A.
A1  - Gupta, Jalaj
A1  - Bennecke, Moritz
A1  - Oliveira, Tiago de
A1  - Ramakrishnan, Mallika
A1  - Braczynski, Anne Kristin
A1  - Richter, Benjamin
A1  - Beli, Petra
A1  - Hu, Yinling
A1  - Saleh, Maya
A1  - Mittelbronn, Michel Guy André
A1  - Đikić, Ivan
A1  - Greten, Florian
T1  - IKKα controls ATG16L1 degradation to prevent ER stress during inflammation
T2  - Journal of experimental medicine
N2  - Inhibition of the IκB kinase complex (IKK) has been implicated in the therapy of several chronic inflammatory diseases including inflammatory bowel diseases. In this study, using mice with an inactivatable IKKα kinase (IkkαAA/AA), we show that loss of IKKα function markedly impairs epithelial regeneration in a model of acute colitis. Mechanistically, this is caused by compromised secretion of cytoprotective IL-18 from IKKα-mutant intestinal epithelial cells because of elevated caspase 12 activation during an enhanced unfolded protein response (UPR). Induction of the UPR is linked to decreased ATG16L1 stabilization in IkkαAA/AA mice. We demonstrate that both TNF-R and nucleotide-binding oligomerization domain stimulation promote ATG16L1 stabilization via IKKα-dependent phosphorylation of ATG16L1 at Ser278. Thus, we propose IKKα as a central mediator sensing both cytokine and microbial stimulation to suppress endoplasmic reticulum stress, thereby assuring antiinflammatory function during acute intestinal inflammation.
Y1  - 2017
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/43957
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-439578
SN  - 1540-9358
SN  - 0022-1007
N1  - © 2017 Diamanti et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).
VL  - 214
IS  - 2
SP  - 423
EP  - 437
PB  - Rockefeller Univ. Press
CY  - New York, NY
ER  -