학술논문
TBK1 phosphorylation activates LIR-dependent degradation of the inflammation repressor TNIP1.
Document Type
Article
Author
Jianwen Zhou; Lander Rasmussen, Nikoline; Lauritz Olsvik, Hallvard; Akimov, Vyacheslav; Zehan Hu; Evjen, Gry; Kaeser-Pebernard, Stéphanie; Sankar, Devanarayanan Siva; Roubaty, Carole; Verlhac, Pauline; van de Beck, Nicole; Reggiori, Fulvio; Abudu, Yakubu Princely; Blagoev, Blagoy; Lamark, Trond; Johansen, Terje; Dengjel, Jörn
Source
Subject
Language
ISSN
0021-9525
Abstract
Limitation of excessive inflammation due to selective degradation of pro-inflammatory proteins is one of the cytoprotective functions attributed to autophagy. In the current study, we highlight that selective autophagy also plays a vital role in promoting the establishment of a robust inflammatory response. Under inflammatory conditions, here TLR3-activation by poly(I:C) treatment, the inflammation repressor TNIP1 (TNFAIP3 interacting protein 1) is phosphorylated by Tank-binding kinase 1 (TBK1) activating an LIR motif that leads to the selective autophagy-dependent degradation of TNIP1, supporting the expression of pro-inflammatory genes and proteins. This selective autophagy efficiently reduces TNIP1 protein levels early (0-4 h) upon poly(I:C) treatment to allow efficient initiation of the inflammatory response. At 6 h, TNIP1 levels are restored due to increased transcription avoiding sustained inflammation. Thus, similarly as in cancer, autophagy may play a dual role in controlling inflammation depending on the exact state and timing of the inflammatory response. [ABSTRACT FROM AUTHOR]