Lys29-linkage of ASK1 by Skp1-Cullin 1-Fbxo21 ubiquitin ligase complex is required for antiviral innate response.
Zhou YuTaoyong ChenXuelian LiMingjin YangSongqing TangXuhui ZhuYan GuXiaoping SuMeng XiaWeihua LiXuemin ZhangQingqing WangXuetao CaoJianli WangPublished in: eLife (2016)
Protein ubiquitination regulated by ubiquitin ligases plays important roles in innate immunity. However, key regulators of ubiquitination during innate response and roles of new types of ubiquitination (apart from Lys48- and Lys63-linkage) in control of innate signaling have not been clearly understood. Here we report that F-box only protein Fbxo21, a functionally unknown component of SCF (Skp1-Cul1-F-box protein) complex, facilitates Lys29-linkage and activation of ASK1 (apoptosis signal-regulating kinase 1), and promotes type I interferon production upon viral infection. Fbxo21 deficiency in mice cells impairs virus-induced Lys29-linkage and activation of ASK1, attenuates c-Jun N-terminal kinase (JNK) and p38 signaling pathway, and decreases the production of proinflammatory cytokines and type I interferon, resulting in reduced antiviral innate response and enhanced virus replication. Therefore Fbxo21 is required for ASK1 activation via Lys29-linkage of ASK1 during antiviral innate response, providing mechanistic insights into non-proteolytic roles of SCF complex in innate immune response.
Keyphrases
- immune response
- dendritic cells
- signaling pathway
- genome wide
- induced apoptosis
- hiv testing
- binding protein
- cell cycle arrest
- toll like receptor
- cell death
- endoplasmic reticulum stress
- type diabetes
- men who have sex with men
- oxidative stress
- epithelial mesenchymal transition
- metabolic syndrome
- small molecule
- protein kinase
- high fat diet induced
- human immunodeficiency virus
- high density
- gene expression
- adipose tissue
- insulin resistance
- hiv infected