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 Beck, Nicole Reggiori, Fulvio Abudu, Yakubu Princely Blagoev, Blagoy Lamark, Trond Johansen, Terje Dengjel, Jörn 2022-12-27 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 TBK1 (Tank-binding kinase 1) activating a LIR motif that leads to the selective autophagy-dependent degradation of TNIP1, supporting 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. application/pdf https://folia.unifr.ch/global/documents/323024 https://folia.unifr.ch/documents/323024/files/zhou_2022_finalmanuscript.pdf https://folia.unifr.ch/documents/323024/files/zhou_2022_finalsupplements.pdf eng info:eu-repo/semantics/altIdentifier/doi/10.1083/jcb.202108144 info:eu-repo/semantics/altIdentifier/issn/0021-9525 info:eu-repo/semantics/openAccess CC BY-NC-SA Journal of Cell Biology. - Rockefeller University Press. - 2022, vol. 222, no. 2 Cell Biology Biochemistry Cell death and autophagy Cell signaling Immunology info:eu-repo/classification/udc/57/59 TBK1 phosphorylation activates LIR-dependent degradation of the inflammation repressor TNIP1 http://purl.org/coar/resource_type/c_6501