The inflammation repressor TNIP1/ABIN-1 is degraded by autophagy following TBK1 phosphorylation of its LIR

ABSTRACT

The inflammatory repressor TNIP1/ABIN-1 is important for keeping in check inflammatory and cell-death pathways to avoid potentially dangerous sustained activation of these pathways. We have now found that TNIP1 is rapidly degraded by selective macroautophagy/autophagy early (0–4 h) after activation of TLR3 by poly(I:C)-treatment to allow expression of pro-inflammatory genes and proteins. A few hours later (6 h), TNIP1 levels rise again to counteract sustained inflammatory signaling. TBK1-mediated phosphorylation of a TNIP1 LIR motif regulates selective autophagy of TNIP1 by stimulating interaction with Atg8-family proteins. This is a novel level of regulation of TNIP1, whose protein level is crucial for controlling inflammatory signaling.

KEYWORDS:

• ABIN-1
• Atg8
• autophagy
• inflammation
• LIR
• TBK1
• TNIP1

Disclosure statement

The authors declare that they have no conflict of interest.

Correction Statement

This article has been republished with minor changes. These changes do not impact the academic content of the article.

Additional information

Funding

This work was funded by the TOPPFORSK program of the Research Council of Norway (grant number 249884) and the Norwegian Cancer Society (grant number 190214) to TJ., the Swiss National Science Foundation, the Canton and University of Fribourg and the Novartis Foundation for Medical-Biological Research to JD.