TY - JOUR
T1 - MAVS recruits multiple ubiquitin E3 ligases to activate antiviral signaling cascades
AU - Liu, Siqi
AU - Chen, Jueqi
AU - Cai, Xin
AU - Wu, Jiaxi
AU - Chen, Xiang
AU - Wu, You Tong
AU - Sun, Lijun
AU - Chen, Zhijian J.
PY - 2013/8/14
Y1 - 2013/8/14
N2 - RNA virus infections are detected by the RIG-I family of receptors, which induce type-I interferons through the mitochondrial protein MAVS. MAVS forms large prion-like polymers that activate the cytosolic kinases IKK and TBK1, which in turn activate NF-κB and IRF3, respectively, to induce interferons. Here we show that MAVS polymers recruit several TRAF proteins, including TRAF2, TRAF5, and TRAF6, through distinct TRAF-binding motifs. Mutations of these motifs that disrupted MAVS binding to TRAFs abrogated its ability to activate IRF3. IRF3 activation was also abolished in cells lacking TRAF2, 5, and 6. These TRAF proteins promoted ubiquitination reactions that recruited NEMO to the MAVS signaling complex, leading to the activation of IKK and TBK1. These results delineate the mechanism of MAVS signaling and reveal that TRAF2, 5, and 6, which are normally associated with NF-κB activation, also play a crucial role in IRF3 activation in antiviral immune responses.
AB - RNA virus infections are detected by the RIG-I family of receptors, which induce type-I interferons through the mitochondrial protein MAVS. MAVS forms large prion-like polymers that activate the cytosolic kinases IKK and TBK1, which in turn activate NF-κB and IRF3, respectively, to induce interferons. Here we show that MAVS polymers recruit several TRAF proteins, including TRAF2, TRAF5, and TRAF6, through distinct TRAF-binding motifs. Mutations of these motifs that disrupted MAVS binding to TRAFs abrogated its ability to activate IRF3. IRF3 activation was also abolished in cells lacking TRAF2, 5, and 6. These TRAF proteins promoted ubiquitination reactions that recruited NEMO to the MAVS signaling complex, leading to the activation of IKK and TBK1. These results delineate the mechanism of MAVS signaling and reveal that TRAF2, 5, and 6, which are normally associated with NF-κB activation, also play a crucial role in IRF3 activation in antiviral immune responses.
UR - http://www.scopus.com/inward/record.url?scp=84882705934&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84882705934&partnerID=8YFLogxK
U2 - 10.7554/eLife.00785.001
DO - 10.7554/eLife.00785.001
M3 - Article
C2 - 23951545
AN - SCOPUS:84882705934
SN - 2050-084X
VL - 2013
JO - eLife
JF - eLife
IS - 2
M1 - e00785
ER -