TBK1 phosphorylation activates LIR-dependent degradation of the inflammation repressor TNIP1

Jianwen Zhou, Nikoline Lander Rasmussen, Hallvard Lauritz Olsvik, Vyacheslav Akimov, Zehan Hu, Gry Evjen, Stéphanie Kaeser-Pebernard, Devanarayanan Siva Sankar, Carole Roubaty, Pauline Verlhac, Nicole van de Beck, Fulvio Reggiori, Yakubu Princely Abudu, Blagoy Blagoev, Trond Lamark, Terje Johansen, Jörn Dengjel

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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.

Original languageEnglish
Article numbere202108144
JournalThe Journal of Cell Biology
Issue number2
Publication statusPublished - 6. Feb 2023


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