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作 者:Dandan Yang Gaofeng Pei Shuangshuang Dong Wenhao Zhang Haiteng Deng Xueqiang Zhao Pilong Li Xin Lin
机构地区:[1]Institute for Immunology,School of Medicine,Tsinghua University,Beijing 100084,China [2]Beijing Advanced Innovation Center for Structural Biology,School of Life Sciences,Tsinghua University,Beijing 100084,China [3]Tsinghua-Peking Center for Life Sciences,Beijing 100084,China [4]MOE Key Laboratory of Bioinformatics,School of Life Sciences,Tsinghua University,Beijing 100084,China
出 处:《Science China(Life Sciences)》2023年第2期283-297,共15页中国科学(生命科学英文版)
基 金:supported by the National Natural Science Foundation of China(81570211,31670904);the Tsinghua-Peking Center for Life Sciences。
摘 要:B-cell lymphoma 10(Bcl10) is a scaffolding protein that functions as an upstream regulator of NF-κB signaling by forming a complex with Mucosa-associated lymphoid tissue lymphoma translocation protein 1(Malt1) and CARD-coiled coil protein family. This study showed that Bcl10 was involved in type I interferon(IFN) expression in response to DNA virus infection and that Bcl10-deficient mice were more susceptible to Herpes simplex virus 1(HSV-1) infection than control mice. Mechanistically,DNA virus infection can trigger Bcl10 recruitment to the STING-TBK1 complex, leading to Bcl10 phosphorylation by TBK1.The phosphorylated Bcl10 undergoes droplet-like condensation and forms oligomers, which induce TBK1 phosphorylation and translocation to the perinuclear region. The activated TBK1 phosphorylates IRF3, which induces the expression of type I IFNs.This study elucidates that Bcl10 induces an innate immune response by undergoing droplet-like condensation and participating in signalosome formation downstream of the c GAS-STING pathway.
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