Sumoylation Promotes the Stability of the DNA Sensor cGAS and the Adaptor STING to Regulate the Kinetics of Response to DNA Virus.
Immunity.
2016 Sep 20;45(3):555-69. doi: 10.1016/j.immuni.2016.08.014. Epub 2016 Sep 13.
Sumoylation Promotes the Stability of the DNA Sensor cGAS and the Adaptor STING to Regulate theKinetics of Response to DNA Virus.
1College of Life Sciences, Wuhan University, Wuhan, China, 430072; Medical Research Institute, Wuhan University, Wuhan, China, 430072.
2Medical Research Institute, Wuhan University, Wuhan, China, 430072.
3College of Life Sciences, Wuhan University, Wuhan, China, 430072.
4College of Life Sciences, Wuhan University, Wuhan, China, 430072; Medical Research Institute, Wuhan University, Wuhan, China, 430072; Collaborative Innovation Center for Viral Immunology, Wuhan University, Wuhan, China, 430072. Electronic address: shuh@whu.edu.cn.
Abstract
During viral infection, sensing of cytosolic
DNA
by the cyclic GMP-AMP synthase (
cGAS
) activates the
adaptor
protein
STING
and triggers an antiviral
response
. Little is known about the mechanisms that determine the
kinetics
of activation and deactivation of the
cGAS
-
STING
pathway, ensuring effective but controlled innate antiviral responses. Here we found that the ubiquitin ligase Trim38 targets
cGas
for
sumoylation
in uninfected cells and during the early phase of viral infection.
Sumoylation
of
cGas
prevented its polyubiquitination and degradation. Trim38 also sumoylated
Sting
during the early phase of viral infection, promoting both
Sting
activation and protein
stability
. In the late phase of infection,
cGas
and
Sting
were desumoylated by Senp2 and subsequently degraded via proteasomal and chaperone-mediated autophagy pathways, respectively. Our findings reveal an essential role for Trim38 in the innate immune
response
to
DNA
virus
and provide insight into the mechanisms that ensure optimal activation and deactivation of the
cGAS
-
STING
pathway.
Copyright © 2016 Elsevier Inc. All rights reserved.