DYRK2 Negatively Regulates Type I Interferon Induction by Promoting TBK1 Degradation via Ser527 Phosphorylation

PLoS Pathogens

Shu Li¹  Bo Zhong²  Wei Pan²  Po Tien²  Hong-Bing Shu²  Shuwen Wu²  Tai An² 

[1] The College of Basic Medical Science, Shaanxi University of Chinese Medicine, Xi’an, China;The College of Life Sciences, State Key Laboratory of Virology, Modern Virology Research Center, Wuhan University, Wuhan, China

关键词: HEK 293 cells;    Phosphorylation;    Ubiquitination;    Interferons;    Transcription factors;    RNA interference;    Plasmid construction;    Immunoblotting;   

DOI  :  10.1371/journal.ppat.1005179

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Viral infection activates the transcription factors NF-κB and IRF3, which contribute to the induction of type I interferons (IFNs) and cellular antiviral responses. Protein kinases play a critical role in various signaling pathways by phosphorylating their substrates. Here, we identified dual-specificity tyrosine-(Y)-phosphorylation-regulated kinase 2 (DYRK2) as a negative regulator of virus-triggered type I IFN induction. DYRK2 inhibited the virus-triggered induction of type I IFNs and promoted the K48-linked ubiquitination and degradation of TANK-binding kinase 1 (TBK1) in a kinase-activity-dependent manner. We further found that DYRK2 phosphorylated Ser527 of TBK1, which is essential for the recruitment of NLRP4 and for the E3 ubiquitin ligase DTX4 to degrade TBK1. These findings suggest that DYRK2 negatively regulates virus-triggered signaling by targeting TBK1 for phosphorylation and priming it for degradation, and these data provide new insights into the molecular mechanisms that dictate the cellular antiviral response.

【 授权许可】

CC BY