Negative regulation of virus-triggered IFN-beta signaling pathway by alternative splicing of TBK1.
Induction of Type I IFNs is a central event in antiviral responses and must be tightly controlled. The protein kinase TBK1 is critically involved in virus-triggered type I IFN signaling. In this study, we identify an alternatively spliced isoform of TBK1, termed TBK1s, which lacks exons 3-6. Upon Sendai virus (SeV) infection, TBK1s is induced in both human and mouse cells and binds to RIG-1, disrupting the interaction between RIG-I and VISA. Consistent with that result, overexpression of TBK1s inhibits IRF3 nuclear translocation and leads to a shutdown of SeV-triggered IFN-beta production. Taken together, our data indicate that TBK1s plays an inhibitory role in virus-triggered IFN-beta signaling pathways.
Deng
Weiwen
W
Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
Shi
Mude
M
Han
Meifang
M
Zhong
Jin
J
Li
Zhenhu
Z
Li
Weina
W
Hu
Yu
Y
Yan
Lingchen
L
Wang
Jie
J
He
Ying
Y
Tang
Hong
H
Deubel
Vincent
V
Luo
Xiaoping
X
Ning
Qin
Q
Sun
Bing
B
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D017398:Alternative Splicing; D000818:Animals; D002460:Cell Line; D004790:Enzyme Induction; D006801:Humans; D050838:Interferon Regulatory Factor-3 / Q000378:metabolism; D016899:Interferon-beta / Q000096:biosynthesis*; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D009419:Nerve Tissue Proteins / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis*; D021381:Protein Transport; D011956:Receptors, Cell Surface; D018168:Receptors, Retinoic Acid / Q000378:metabolism; D010253:Respirovirus Infections / Q000378:metabolism*; D029082:Sendai virus; D015398:Signal Transduction; D000097905:Roundabout Proteins
D048868:Adaptor Proteins, Signal Transducing; D050838:Interferon Regulatory Factor-3; D016899:Interferon-beta; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D017346:Protein Serine-Threonine Kinases; D011956:Receptors, Cell Surface; D018168:Receptors, Retinoic Acid; C494232:IRF3 protein, human; C494233:Irf3 protein, mouse; C505371:MAVS protein, human; C437968:PLAAT4 protein, human; C118348:Robo3 protein, mouse; D000097905:Roundabout Proteins; C498588:Tbk1 protein, mouse; C403191:TBK1 protein, human; C512612:MAVS protein, mouse