TBK1 phosphorylation activates LIR-dependent degradation of the inflammation repressor TNIP1.
Jianwen ZhouNikoline Lander RasmussenHallvard Lauritz OlsvikVyacheslav AkimovZehan HuGry EvjenStéphanie Kaeser-PebernardDevanarayanan Siva SankarCarole RoubatyPauline VerlhacNicole van de BeckFulvio M ReggioriYakubu Princely AbuduBlagoy BlagoevTrond LamarkTerje JohansenJoern DengjelPublished in: The Journal of cell biology (2022)
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.
Keyphrases
- oxidative stress
- inflammatory response
- cell death
- signaling pathway
- endoplasmic reticulum stress
- lipopolysaccharide induced
- toll like receptor
- lps induced
- binding protein
- protein kinase
- transcription factor
- poor prognosis
- amino acid
- dna methylation
- protein protein
- squamous cell carcinoma
- gene expression
- genome wide
- body mass index
- long non coding rna
- weight loss
- combination therapy
- replacement therapy
- smoking cessation