TBK1 phosphorylation activates LIR-dependent degradation of the inflammation repressor TNIP1
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AuthorZhou, Jianwen; Rasmussen, Nikoline Lander; Olsvik, Hallvard Lauritz; Akimov, Vyacheslav; Hu, Zehan; 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
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.
PublisherRockefeller University Press
CitationZhou, Rasmussen, Olsvik, Akimov, Hu, Evjen, Kaeser-Pebernard, Sankar, Roubaty, Verlhac, van de Beck, Reggiori, Abudu, Blagoev, Lamark, Johansen, Dengjel. TBK1 phosphorylation activates LIR-dependent degradation of the inflammation repressor TNIP1. Journal of Cell Biology. 2023;222(2)
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