The E3 ubiquitin ligase TRIM21 negatively regulates the innate immune response to intracellular double-stranded DNA.
The E3 ubiquitin ligase TRIM21 negatively regulates the innate immune response to intracellular double-stranded DNA.
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DDX 41是髓样树突状细胞（mDC）中的细胞内双链DNA（dsDNA）的传感器，其通过信号传导衔接子STING触发I型干扰素应答。我们鉴定了E3连接酶TRIM 21作为DDX 41相互作用蛋白，并发现TRIM 21的敲低或缺陷导致对细胞内dsDNA和DNA病毒的I型干扰素应答增强。TRIM 21的过表达导致DDX 41的更多降解和响应于细胞内dsDNA的干扰素-β（IFN-β）的更少产生。TRIM 21的SPRY-PRY结构域与DDX 41的DEADc结构域相互作用。DDX 41的Lys 9和Lys 115是TRIM 21介导的泛素化的靶点。因此，TRIM 21是干扰素诱导的E3连接酶，其诱导DDX 41的Lys 48（K48）连接的泛素化和降解，并负调节对细胞内dsDNA的先天免疫应答。
DDX41 is a sensor of intracellular double-stranded DNA (dsDNA) in myeloid dendritic cells (mDCs) that triggers a type I interferon response via the signaling adaptor STING. We identified the E3 ligase TRIM21 as a DDX41-interacting protein and found that knockdown of or deficiency in TRIM21 resulted in enhanced type I interferon responses to intracellular dsDNA and DNA viruses. Overexpression of TRIM21 resulted in more degradation of DDX41 and less production of interferon-β (IFN-β) in response to intracellular dsDNA. The SPRY-PRY domain of TRIM21 interacted with the DEADc domain of DDX41. Lys9 and Lys115 of DDX41 were the targets of TRIM21-mediated ubiquitination. TRIM21 is therefore an interferon-inducible E3 ligase that induces the Lys48 (K48)-linked ubiquitination and degradation of DDX41 and negatively regulates the innate immune response to intracellular dsDNA.
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影响因子：
30.5
作者：
Buerckstuemmer, Tilmann;Baumann, Christoph;Superti-Furga, Giulio
通讯作者：
Superti-Furga, Giulio
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DOI：
10.1073/pnas.0700544104
发表时间：
2007-07-10
影响因子：
11.1
作者：
Diao, Feici;Li, Shu;Shu, Hong-Bing
通讯作者：
Shu, Hong-Bing
影响因子：
30.5
作者：
Kawai, T;Takahashi, K;Akira, S
通讯作者：
Akira, S
影响因子：
30.5
作者：
通讯作者：
--
影响因子：
5.4
作者：
Oshiumi, Hiroyuki;Sakai, Keisuke;Seya, Tsukasa
通讯作者：
Seya, Tsukasa