Prof. Baoxue Ge’s group discovered an essential role of CK1ε in regulating anti-virus innate immune response
Source：Baoxue Ge
2016-04-12
On February 29, 2016, Nature Immunology published a research article entitled ‘The kinase CK1ε controls the antiviral immune response by phosphorylating the signaling adaptor TRAF3’, from Prof. Baoxue Ge’s group of Tongji University School of Medicine. The authors found that CK1ε plays a pivotal role in antiviral innate immune response by phosphorylating TRAF3.
TNF receptor-associated factors (TRAF1-6) are scaffold proteins that link receptors of the IL-1R/Toll and TNF receptor family to signaling cascades. They serve as a docking platform for a variety of regulators of signaling transduction and are themselves often regulated at the posttranslational level. As a highly versatile regulator of both innate immunity and adaptive immunity, TRAF3 undertakes its multiple functions in highly receptor- and cell type-dependent manner. Although ubiquitination of TRAF3 is extensively studied, how its phosphorylation is regulated is still unknown. Besides, as a conserved Ser/Thr kinase family, CK1ε play a crucial role in growth and development, but whether and how these serine-threonine kinases regulate immune responses is poorly understood.
The authors performed a large-scale screening of compounds and found that IC261, a CK1ε specific inhibitor, suppressed virus infection induced IFN-β production. Deficiency of CK1ε suppressed the production of type I interferon in response to virus infection or LPS stimulation and CK1ε-deficient mice were more susceptible to virus infection. CK1ε interacts with and phosphorylates TRAF3 at Ser349, which thereby promoted the Lys63 (K63)-linked ubiquitination of TRAF3 and subsequent recruitment of the kinase TBK1 to TRAF3.
The studies about the roles and mechanisms of CK1ε in the regulation of IFN-β may provide new mechanistic explanations for TRAF3 phosphorylation and bring a new potential target for the treatment of autoimmune diseases.
This work was supported by grants from the National Basic Research Program of China (973 Programs 2012CB578100 and 2011CB505000) and the National Natural Science Foundation of China (projects 81330069 and 31030028).Other researchers from Fudan University and Beijing Institute of Microbiology and Epidemiology also contribute to this work. They are Dr. Haojie Lu from Fudan University and Dr. Chengfeng Qin from Beijing Institute of Microbiology and Epidemiology.
TNF receptor-associated factors (TRAF1-6) are scaffold proteins that link receptors of the IL-1R/Toll and TNF receptor family to signaling cascades. They serve as a docking platform for a variety of regulators of signaling transduction and are themselves often regulated at the posttranslational level. As a highly versatile regulator of both innate immunity and adaptive immunity, TRAF3 undertakes its multiple functions in highly receptor- and cell type-dependent manner. Although ubiquitination of TRAF3 is extensively studied, how its phosphorylation is regulated is still unknown. Besides, as a conserved Ser/Thr kinase family, CK1ε play a crucial role in growth and development, but whether and how these serine-threonine kinases regulate immune responses is poorly understood.
The authors performed a large-scale screening of compounds and found that IC261, a CK1ε specific inhibitor, suppressed virus infection induced IFN-β production. Deficiency of CK1ε suppressed the production of type I interferon in response to virus infection or LPS stimulation and CK1ε-deficient mice were more susceptible to virus infection. CK1ε interacts with and phosphorylates TRAF3 at Ser349, which thereby promoted the Lys63 (K63)-linked ubiquitination of TRAF3 and subsequent recruitment of the kinase TBK1 to TRAF3.
The studies about the roles and mechanisms of CK1ε in the regulation of IFN-β may provide new mechanistic explanations for TRAF3 phosphorylation and bring a new potential target for the treatment of autoimmune diseases.
This work was supported by grants from the National Basic Research Program of China (973 Programs 2012CB578100 and 2011CB505000) and the National Natural Science Foundation of China (projects 81330069 and 31030028).Other researchers from Fudan University and Beijing Institute of Microbiology and Epidemiology also contribute to this work. They are Dr. Haojie Lu from Fudan University and Dr. Chengfeng Qin from Beijing Institute of Microbiology and Epidemiology.
