摘要: Cyclic GMP-AMP synthase (cGAS) senses cytosolic DNA during viral infection and catalyzes synthesis of the dinucleotide cGAMP, which activates the adaptor STING to initiate antiviral responses. Here we found that deficiency in the carboxypeptidase CCP5 or CCP6 led to susceptibility to DNA viruses. CCP5 and CCP6 were required for activation of the transcription factor IRF3 and interferons. Polyglutamylation of cGAS by the enzyme TTLL6 impeded its DNA-binding ability, whereas TTLL4-mediated monoglutamylation of cGAS blocked its synthase activity. Conversely, CCP6 removed the polyglutamylation of cGAS, whereas CCP5 hydrolyzed the monoglutamylation of cGAS, which together led to the activation of cGAS. Therefore, glutamylation and deglutamylation of cGAS tightly modulate immune responses to infection with DNA viruses.
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期刊:
NATURE IMMUNOLOGY
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分类:
生物学
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生物物理学
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免疫学
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引用:
ChinaXiv:201605.00717
(或此版本
ChinaXiv:201605.00717V1)
DOI:10.12074/201605.00717V1
CSTR:32003.36.ChinaXiv.201605.00717.V1
- 推荐引用方式:
Xia, Pengyan,Ye, Buqing,Wang, Shuo,Du, Ying,Xiong, Zhen,Fan, Zusen,Zhu, Xiaoxiao,Xiong, Zhen,Fan, Zusen,Tian, Yong,Tian, Yong,.(2016).Glutamylation of the DNA sensor cGAS regulates its binding and synthase activity in antiviral immunity.中国生物工程预印本出版平台.[ChinaXiv:201605.00717]
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