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

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 r...

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Detalles Bibliográficos
Autores principales: Zhou, 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 Beek, Nicole, Reggiori, Fulvio, Abudu, Yakubu Princely, Blagoev, Blagoy, Lamark, Trond, Johansen, Terje, Dengjel, Jörn
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Rockefeller University Press 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9797988/
https://www.ncbi.nlm.nih.gov/pubmed/36574265
http://dx.doi.org/10.1083/jcb.202108144
Descripción
Sumario: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.